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The genus Laelius Ashmead, 1893 (Hymenoptera, Bethylidae) is a cosmopolitan bethylid genus with 68 valid species distributed across most zoogeographic regions worldwide. This taxonomic study on Korean species of Laelius has led to the description of four new species, namely L. afores sp. nov., L. atratus sp. nov., L. sulcatus sp. nov., and L. tricuspis sp. nov. Additionally, illustrations of the diagnostic characteristics of each species are provided, along with an updated key for 11 Laelius species from the Eastern Palaearctic region.

Abstract A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM. ClinicalTrials.gov identifier: NCT05739292.

Abstract Varroa mites, notorious for parasitizing honeybees, are generally classified as Varroidae. Their extremely modified morphologies and behaviors have led to debates regarding their phylogenetic position and classification as an independent family. In this study, two different datasets were employed to reconstruct the phylogenies of Varroa mites and related Laelapidae species: (1) 9257 bp from the whole 13 mitochondrial protein-coding genes of 24 taxa, (2) 3158 bp from 113 taxa using Sanger sequencing of four nuclear loci. Both mitochondrial and nuclear analyses consistently place Varroa mites within the Laelapidae. Here we propose to place Varroa mites in the subfamily Varroinae stat. nov., which represents a highly morphologically adapted group within the Laelapidae. Ancestral state reconstructions reveal that bee-associated lifestyles evolved independently at least three times within Laelapidae, with most phoretic traits originating from free-living ancestors. Our revised classification and evolutionary analyses will provide new insight into understanding the Varroa mites.

Abstract Background Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. Methods This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. Results From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). Conclusions This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Artificial intelligence (AI) is increasingly used to solve multi‐objective problems and reduce the turnaround times of semiconductor processes. However, only brief AI explanations are available for process/device/circuit engineers to provide holistic feedback on the manufactured results. Herein, linear/nonlinear variation decomposition (LVD/NLVD) of neural networks is demonstrated to quantitatively evaluate the influence of unit processes on the figure of merit (FoM) and co‐analyze the unit process influences with device characteristic behaviors. The NLVD can evaluate the output variation from each input of neural networks in an individual sample, although neural networks are not available in an analytic form. The NLVD is successfully verified by confirming that a) the output and summation of all decomposed output variations perfectly coincide and b) the process influences on the FoM are decomposed to 6.01–54.86% more accurately compared with those of LVD in 1Y nm node dynamic random‐access memory test vehicles with a baseline and split tests introducing high‐k metal gates with a minimum gate length of 1 A nm node for further node scaling. The approaches identify defective processes and defect mechanisms in each sample and wafer, which enhance causal analyses for individual cases in diverse fields based on regression artificial neural networks.

BackgroundDepressive disorders have substantial global implications, leading to various social consequences, including decreased occupational productivity and a high disability burden. Early detection and intervention for clinically significant depression have gained attention; however, the existing depression screening tools, such as the Center for Epidemiologic Studies Depression Scale, have limitations in objectivity and accuracy. Therefore, researchers are identifying objective indicators of depression, including image analysis, blood biomarkers, and ecological momentary assessments (EMAs). Among EMAs, user-generated text data, particularly from diary writing, have emerged as a clinically significant and analyzable source for detecting or diagnosing depression, leveraging advancements in large language models such as ChatGPT. ObjectiveWe aimed to detect depression based on user-generated diary text through an emotional diary writing app using a large language model (LLM). We aimed to validate the value of the semistructured diary text data as an EMA data source. MethodsParticipants were assessed for depression using the Patient Health Questionnaire and suicide risk was evaluated using the Beck Scale for Suicide Ideation before starting and after completing the 2-week diary writing period. The text data from the daily diaries were also used in the analysis. The performance of leading LLMs, such as ChatGPT with GPT-3.5 and GPT-4, was assessed with and without GPT-3.5 fine-tuning on the training data set. The model performance comparison involved the use of chain-of-thought and zero-shot prompting to analyze the text structure and content. ResultsWe used 428 diaries from 91 participants; GPT-3.5 fine-tuning demonstrated superior performance in depression detection, achieving an accuracy of 0.902 and a specificity of 0.955. However, the balanced accuracy was the highest (0.844) for GPT-3.5 without fine-tuning and prompt techniques; it displayed a recall of 0.929. ConclusionsBoth GPT-3.5 and GPT-4.0 demonstrated relatively reasonable performance in recognizing the risk of depression based on diaries. Our findings highlight the potential clinical usefulness of user-generated text data for detecting depression. In addition to measurable indicators, such as step count and physical activity, future research should increasingly emphasize qualitative digital expression.

The genus Plutarchia is discovered in the Palearctic region for the first time. In this study, we report a newly described and newly recorded species from South Korea: P. fuscipennata sp. nov., and P. malabarica Narendran & Padmasenan, 1990, respectively. The host association of Plutarchia malabarica reared from leaf-miner flies (Diptera: Agromyzidae) attacking the seeds of Pueraria lobata (Willd.) Ohwi (Fabaceae) has been unknown until now. A key to the South Korean species and descriptions of the new species are also provided.

Abstract Objective Despite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as “insufficient” or “sufficient” by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values. Results A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L. Interpretation This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia‐related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Abstract JBPOS0101 is a new antiepileptic drug and is a substrate of UDP‐glucuronosyltransferases (UGTs) in in vitro test. In vitro experiments showed different results regarding whether JBPOS0101 induces (EC50 136 μM) or inhibits (IC50 95.4–386.5 μM) cytochrome P450 (CYP) 3A4. As co‐medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug–drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two‐cohort, open‐label, fixed‐sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co‐administered with MDZ after oral doses of JBPOS0101 for 7 days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7 days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co‐administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co‐administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.

Abstract Fexuprazan, a novel potassium‐competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti‐inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open‐label, multicenter, six‐sequence, one‐way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1–2 days in the second period. Serial blood samples for PK analysis were collected until 48‐ or 72‐h post‐dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration–time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co‐administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02–1.46) and 1.19 (1.00–1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

Abstract Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator‐activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone‐induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta‐alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post‐dose. Pioglitazone‐dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.

This study proposes a robust $H_{\infty }$ guaranteed cost controller (RHGCC) and its design method for set-point tracking control of quadrotor unmanned aerial vehicle (UAV) considering both model uncertainties and external disturbances. To guarantee a certain level of optimal performance against the effects of model uncertainties and external disturbances such as wind gusts, the proposed RHGCC integrates the $H_{\infty }$ control method with guaranteed cost control. Furthermore, a linear matrix inequality (LMI)-based controller design condition is proposed, guaranteeing not only a certain level of linear quadratic (LQ) cost but also the upper bound of the disturbance attenuation level in terms of $H_{\infty }$ norm. The proposed RHGCC is designed for the position and attitude control of the quadrotor UAV, enabling both the position and attitude of quadrotor UAV to be robust against external disturbances. Simulation results validate the effectiveness of the proposed RHGCC and demonstrate that the proposed method outperforms conventional methods in reducing tracking errors against disturbances. Especially, the proposed method significantly reduces the $H_{\infty }$ norm and suppresses disturbances compared to conventional methods.

A floating-point fully homomorphic encryption (FPFHE) is proposed, which is based on torus fully homomorphic encryption equipped with programmable bootstrapping. Specifically, FPFHE for 32-bit and 64-bit floating-point messages are implemented, the latter showing the state-of-the-art precision among FHEs. Also, a ciphertext is constructed for checking if an overflow has occurred or not while evaluating arithmetic circuits with the proposed FPFHE, which is useful when the message space or arithmetic circuit is too complex to estimate a bound of outputs such as some deep learning applications. Also, homomorphic algorithms, which are crucial components of overflow detectable (OD)-FPFHE, are constructed. First, a state-of-the-art bootstrapping method of TFHE is extended to bootstrap larger messages by using NTT-friendly integer modulus. Second, a subgaussian analysis method is proposed without assuming independent heuristic on AP/GINX-bootstrapping even if the deterministic gadget decomposition is used. Third, the blind rotation algorithm of TFHE is modified such that any secret key having finite non-zero values can be used while keeping the number of NTT operations the same as when the binary key is used. Fourth, various homomorphic algorithms are proposed such as evaluating min and max, lifting a constant message to the monomial exponent, counting the number of consecutive zeros from the most significant in the fraction, and performing carryover after homomorphic operation of floating-point numbers. Finally, 32-bit and 64-bit OD-FPFHEs are implemented and simulation results are provided to confirm that they work well even for extreme cases. Also, it is verified that homomorphic overflow detection is well-operated.

Two species of orthotyline plant bugs are newly recognized from the Korean Peninsula including the first record of Blepharidopterus angulatus (Fallén, 1807) and Ulmica baicalica (Kulik, 1965). Diagnostic characters of the species are discussed with the illustrations of adult specimens and genitalic structures. A key to the Korean Blepharidopterus species is also presented.

Korean Eucharitidae is reviewed with six species, including four newly recognized species: Gollumiella buffingtoni Heraty, 2004; Losbanus uichancoi Ishii, 1932; Saccharissa vicina (Masi, 1927); and Schizaspidia scutellaris Masi, 1927. In this study, diagnoses and diagnostic character images are provided along with a key to Korean species.

Abstract Decentralized clinical trials (DCTs) leverage digital technologies to reduce dependency on study sites and intermediaries. DCT should be balanced with accessibility and data reliability while meeting regulatory requirements. Here, we conducted a pilot study for functional constipation symptoms to investigate the feasibility of DCT. The study was an open, fully remote, randomized clinical trial in participants who had functional constipation symptoms. Electronic consent was obtained remotely, and study volunteers were screened through web‐based questionnaires. Subjects were randomized to either receive Lactobacillus and vitamin C supplements or vitamin C alone in a 1:1 ratio, which were delivered directly to subjects. Subjects kept track of bowel diaries daily during the 1‐week baseline and 2‐week treatment period using mobile applications. Bowel symptoms and the validity of the records were descriptively evaluated. A total of 30 subjects were randomized and completed the study. A total of 26.7% of subjects resided outside of the metropolitan area. Two‐week Lactobacillus treatments increased the number of defecations (+0.80 vs. +0.46 times per week) and decreased the defecation time (−3.94 h vs. −1.62 h) compared to the comparator group. Overall, 67.1% of bowel diary records were completed in accordance with the schedule whereas 32.9% were not. Implementation of DCTs can facilitate geographic accessibility but should be guaranteed for data reliability. Prompt detection of errors and response using objective metrics would be required.

Abstract Sampling is one of the most important and fundamental processes in field biology. Among many sampling methods in entomology, window traps have long been considered one of the most effective and standardized methods. Unfortunately, the DNA quality of samples collected by window traps is typically low due to incursion by water, mainly via rainfall. Water cannot be avoided in long‐term surveys, even with a roof, due to wind and condensation. As we move into the genomics era, this shortfall in DNA quality has become problematic for molecular biomonitoring, and solutions are urgently needed. In this study, we developed the Water‐Exclusion Trap (WET), a 3D printable long‐term storable bottom collector for window or pitfall traps. The collection medium in WETs does not dilute because water is excluded and evaporation is limited, maximizing DNA preservation. Our field tests show that the WET outperforms conventional traps in preserving DNA quality. Insect samples preserved in WETs in the field had significantly higher PCR success rates and DNA Integrity Numbers compared to conventional traps. The WET addresses a critical challenge in the use of window traps, DNA degradation caused by water intrusion, and represents a significant advancement in fieldwork for genomic research in entomology. We provide the 3D printing template of the WET, enabling immediate, free use for all. Furthermore, it can be easily customized for different environments and purposes, and can be adapted to a variety of other traps, including pitfall traps, funnel traps and more.

Neural compact models are proposed to simplify device‐modeling processes without requiring domain expertise. However, the existing models have certain limitations. Specifically, some models are not parameterized, while others compromise accuracy and speed, which limits their usefulness in multi‐device applications and reduces the quality of circuit simulations. To address these drawbacks, a neural compact modeling framework with a flexible selection of technology‐based model parameters using a two‐stage neural network (NN) architecture is proposed. The proposed neural compact model comprises two NN components: one utilizes model parameters to program the other, which can then describe the current–voltage (I–V) characteristics of the device. Unlike previous neural compact models, this two‐stage network structure enables high accuracy and fast simulation program with integrated circuit emphasis (SPICE) simulation without any trade‐off. The I–V characteristics of 1000 amorphous indium–gallium–zinc‐oxide thin‐film transistor devices with different properties obtained through fully calibrated technology computer‐aided design simulations are utilized to train and test the model and a highly precise neural compact model with an average IDS error of 0.27% and R2 DC characteristic values above 0.995 is acquired. Moreover, the proposed framework outperforms the previous neural compact modeling methods in terms of SPICE simulation speed, training speed, and accuracy.

Abstract Treatment adherence is an underestimated determinant of treatment success. Poor treatment adherence can also affect the efficacy of clinical trials. A combination of multiple adherence‐monitoring methods is required to ensure robustness. We investigated whether multiple adherence‐monitoring methods, including a novel smartwatch‐based monitoring method, would yield reliable and concordant results. In this open, randomized, decentralized clinical trial, vitamin D‐deficient individuals were randomized to an App − only group (an electronic medication diary) or an App + Watch group (i.e., App and smartwatch‐based monitoring) groups after a week run‐in period. The participants received vitamin D supplements (1000 IU) for 12 weeks (two consecutive periods of 6 weeks) with two pill counts (at the sixth week) and biweekly blood samplings for serum 25(OH) vitamin D concentration. Adherence was assessed and compared between the methods. Sixteen participants were enrolled, of which 13 completed the study. Serum 25(OH) vitamin D levels comparably increased in both groups until the first 7 weeks but trended higher in the App + Watch group in the second period. The number of doses recorded by the pill count and App did not differ significantly between the run‐in and Period 1 (p = 0.5534) but became significantly discrepant in Period 2 (p = 0.0225). In contrast, the concordance for smartwatch‐based monitoring was consistent in either period (p = 0.5898 and p = 0.5839, respectively). We explored multiple adherence‐monitoring methods in this pilot feasibility clinical study. Smartwatch‐based adherence monitoring may be an objective and sensitive method for measuring treatment adherence.

Genus Nomada, which includes approximately 800 species, is the largest genus in the subfamily Nomadinae and the sole genus in the tribe Nomadini. Its taxonomic classification is particularly challenging due to high morphological variations, making it one of the most controversial groups in the subfamily. In order to shed light on the complex classification of Nomada species and their tribal position, this study conducted a multi-locus phylogeny using one mitochondrial gene (COI) and five nuclear protein-coding genes (EF1α, Nak, Opsin, Pol Ⅱ, Wingless). The study focused on expanding the knowledge of some East Palearctic species, with the ultimate goal of reviewing species groups of Nomada present in Korea. In this study, we suggest that the ruficornis species group is polyphyletic. Some species should be moved to more appropriate species groups as follows: N. tsunekiana, N. emarginata, and N. flavopicta into the basalis species group; N. aswensis, N. kaguya, and N. taicho into the armata species group.

Abstract Abnormal gastric acidity, including achlorhydria, can act as a significant source of variability in orally administered drugs especially with pH‐sensitive solubility profiles, such as weak bases, potentially resulting in an undesirable therapeutic response. This study aimed to evaluate the utility of physiologically‐based pharmacokinetic (PBPK) modeling in the prediction of gastric pH‐mediated drug exposure by using itraconazole, a weak base, as a case. An itraconazole PBPK model was developed on the mechanistic basis of its absorption kinetics in a middle‐out manner from a stepwise in vitro‐in vivo extrapolation to in vivo refinement. Afterward, an independent prospective clinical study evaluating gastric pH and itraconazole pharmacokinetics (PKs) under normal gastric acidity and esomeprazole‐induced gastric hypoacidity was conducted for model validation. Validation was performed by comparing the predicted data with the clinical observations, and the valid model was subsequently applied to predict PK changes under achlorhydria. The developed itraconazole PBPK model showed reasonable reproducibility for gastric pH‐mediated exposure observed in the clinical investigation. Based on the model‐based simulations, itraconazole exposure was expected to be decreased up to 65% under achlorhydria, and furthermore, gastric pH‐mediated exposure could be mechanistically interpreted according to sequential variation in total solubility, dissolution, and absorption. This study suggested the utility of PBPK modeling in the prediction of gastric pH‐mediated exposure, especially for drugs whose absorption is susceptible to gastric pH. Our findings will serve as a leading model for further mechanistic assessment of exposure depending on gastric pH for various drugs, ultimately contributing to personalized pharmacotherapy.

Three species of genus Aradus Fabricius (A. betulae (Linnaeus), A. betulinus Fallén, and A. gretae Kiritshenko) are newly recognized from the Korean Peninsula. Photographs of habitus and diagnosis are presented for the newly recorded species. The male of Aradus gretae Kiritshenko is described for the first time. A checklist and key to species of the genus Aradus recorded from Korea are provided.

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.

Nippolachnus Matsumura, 1917 is a small aphid genus from the tribe Tuberolachnini (Hemiptera: Lachninae) occurring in Southeast Asia. Species from this genus are quite characteristic and stand out among lachnids for their morphology and ecological associations. We have performed a revision and phylogenetic analyses to elucidate the relationships within Nippolachnus and other representatives of Tuberolachnini. Here, the taxonomy of the genus is revised based on morphological data to include seven species, three of them newly described: Nippolachnus chakrabartii sp. nov. from India, Nippolachnus sinensis sp. nov. from China, and Nippolachnus malayaensis sp. nov. from Indonesia. Nippolachnus appear to be non monophyletic genus and a new genus, Indolachnus gen. nov., is described to accommodate Nippolachnus himalayensis (van der Goot, 1917) as Indolachnus himalayensis (van der Goot, 1917) comb. nov. The new genus is a sister group to the remaining Nippolachnus species, which created a monophyletic clade. Neonippolachnus Shinji, 1924 syn. nov. is recognised as a synonym of Nippolachnus, and Neonippolachnus betulae Shinji, 1924 syn. nov. as a synonym of Nippolachnus micromeli Shinji, 1924. For the first time, a scanning electron microscopy study of the sexual generation of N. piri Matsumura, 1917 has been performed. Apterous and alate viviparous females of N. bengalensis Basu and Hille Ris Lambers, 1968, N. piri, and N. micromeli, and alate viviparous females of N. xitianmushanus Zhang and Zhong, 1982 are re-described and illustrated, as well as apterous and alate viviparous females of I. himalayensis comb. nov. Hitherto unknown morphs of N. micromeli, N. piri, and N. xitianmushanus are described. A lectotype and paralectotypes of N. xitianmushanus are designated herein. Notes on distribution and host plants are given, and keys to apterous and alate viviparous females of the genera Nippolachnus and Indolachnus are also provided.

Sparse partial correlation estimation is a popular topic in high-dimensional data analysis, where nonzero partial correlation represents the conditional dependency between two corresponding variables given the other variables. In the Gaussian graphical model, many methods have been developed using the $\ell _{1}$ regularization to achieve sparsity on conditional dependency. Most of the existing methods impose $\ell _{1}$ penalty on the off-diagonal entries of the precision matrix. This approach may fail to identify the conditional dependencies with partial correlations of moderate magnitudes when the corresponding elements of the precision matrix are relatively small. In this study, we propose a two-stage procedure to estimate sparse partial correlations using scaled Lasso. The proposed procedure resolves the non-convexity of partial correlation estimation by using a consistent estimator of the diagonal elements of the precision matrix from scaled Lasso. Moreover, we develop an efficient algorithm for the proposed method using graphics processing units based on the iterative shrinkage algorithm. Our numerical study shows that the proposed method performs better than the existing methods in terms of edge recovery and the estimation of the partial correlations under the Frobenius norm.

This study deals with a new strategy of the re-assignment for multi-robot seamless coverage tasks using the concept of propagation in a multi-robot surveillance system (MRSS). In the context of MRSSs, multi-robot coverage tasks play a critical role. These tasks require generating paths for two or more robots to cover an entire area, with the objective of minimizing the time needed to complete the task. However, over time, robots may need to be excluded from coverage missions due to issues such as battery charging or malfunctions. It is important to handle these situations efficiently in order to maintain the completeness and balance of the coverage mission. Typically, it can be resolved by either recomputing the coverage algorithm for the remaining robots or redistributing the coverage task of the excluded robot to its neighbors. However, in the proposed method, the amount of coverage area of the excluded robot is equally and efficiently assigned to the remaining robots. First off, a relational graph between robots and a tree based on the excluded robot are sequentially constructed to necessarily know how the robots are geometrically arranged in the given area centered on the excluded robot. The excluded robot becomes the root of the tree, and the depth of the tree indicates the proximity of the coverage areas. Subsequently, the amount of the original coverage area of the excluded robot can be differently assigned to its nearest neighbor robots according to the size of the subtree. Then, the coverage area of the robots corresponding to the second level of the tree are added from the partial coverage area of their parent robot to keep their coverage area balanced, respectively. The similar process is continuously performed, such as ‘propagation’, until the re-assignment of the coverage area over the leaf nodes is complete. Finally, balanced coverage area is re-assigned to the remaining robots, which is time-efficiently computed. Simulations were performed on two occupancy grid maps that were acquired from a simultaneous localization and mapping method. The proposed method was evaluated against conventional methods on three factors such as the balanced re-assignment of the coverage area (Balancing), the variation of the individual coverage area before and after the re-assignment process (Seamless Coverage), and the total computational efficiency over time (Time-efficiency). The coverage area was uniformly re-allocated after the proposed method was applied. In addition, the proposed method had a short calculation time and enables seamless coverage even after re-allocation. In the future, probabilistic maps related to the importance rate, accident rate, and crowds in the coverage area will also be taken into consideration.

Techniques for tagging active neurons with high spatiotemporal precision are limited. Here the authors report soma-targeted CalLight (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression, and generate a conditional ST-Cal-Light knock-in mouse.

In this study, we corrected the misidentified insect pests on yam (Discorea polystachya), based on morphological characters and molecular analysis, and also firstly recorded the species in Korea. The species is a yam borer, Digitivalva hemiglypha Diakonoff & Arita. To accurate pest identification in future utility, genetic divergence within the genus Digitivalva including 43 individuals was calculated by adding samples from Korea and Japan. The intraspecific and interspecific genetic divergences in cytochrome oxidase subunit I, when calculated separately from D. hemiglypha I and D. hemiglypha II, had each constant average values along with other congeneric species: average 0.1% of intraspecific genetic divergence with ranges 0.0–0.7%; average 10.1% of interspecific genetic divergence with ranges 4.0–12.9%. Additionally, Automatic Barcode Gap Discovery results also recognized that two clades of D. hemiglypha were different molecular operational taxonomic units in the substitution models. Consequently, our results indicate that D. hemiglypha I is a correct D. hemiglypha in the cytochrome oxidase subunit I and it also supported by morphological comparison with the holotype of that. All sequences of D. hemiglypha I were nested in the same haplotype, with indicating the rapid dispersal. In further study, D. hemiglypha II will be re-checked as a distinct species of Digitivalva or other genus after examination of their specimens.

Abstract 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.

Abstract Leptonetidae are tiny, rarely encountered spiders that mainly inhabit moist environments, such as caves, leaf litter, and rock piles. Because they are microhabitat specialists, most leptonetid species have short-range endemism, and rarely occur in sympatry. Their small size, relatively simple habitus features and reproductive organ structure increase the difficulty of identification. The identification of leptonetids and other spiders may also be time-consuming due to their sexual dimorphism, polymorphism, and lack of diagnostic characteristics in juveniles. DNA barcoding has been used as an effective tool for species identification to overcome these obstacles. Herein, we conducted a test of DNA barcoding based on 424 specimens of Korean Leptonetidae representing 76 morphospecies. A threshold of 4.2% based on maximum intraspecific genetic divergence was estimated to efficiently differentiate the morphospecies. The species assignments tested by five species delimitation methods (ABGD, ASAP, GMYC, PTP, and bPTP) were consistent with the morphological identifications for only 47 morphospecies (61.8%), indicating many cases of cryptic diversity among the remaining morphospecies. Furthermore, sympatry in leptonetids, which are known to be rare, was revealed to be common in South Korea, especially in epigean species. Our results showed that sympatries within families, congeners, and intraclades potentially occur throughout the entire region of Korea.

Background : 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. Methods : 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. Results : 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). Conclusions: These results indicate that repeat kidney transplantation from living donors is a reasonable choice for patients who have experienced graft loss.

The furva species-group of Nomada from Korea is reviewed in the present study, with one newly recognized species, Nomada pulawskii Tsuneki. Detailed taxonomical description, and illustrations of adults and male genitalia are provided along with a key to species.

Abstract Early embryonic development of the spinal cord requires tight coordination between proliferation of neural progenitors and their differentiation into distinct neuronal cell types to establish intricate neuronal circuits. The Hippo pathway is one of the well-known regulators to control cell proliferation and govern neural progenitor cell number, in which the downstream effector Yes-associated protein (Yap) promotes cell cycle progression. Here we show that an atypical cadherin Fat3, expressed highly in the neural tube, plays a critical role in maintaining proper number of proliferating progenitors. Knockdown of Fat3 in chick neural tube down-regulates expression of the proliferation markers but rather induces the expression of neural markers in the ventricular zone. We further show that deletion of Fat3 gene in mouse neural tube depletes neural progenitors, accompanied by neuronal gene expression in the ventral ventricular zone of the spinal cord. Finally, we found that Fat3 regulates the phosphorylation level of Lats1/2, the upstream kinase of Yap, resulting in dephosphorylation and stabilization of Yap, suggesting Yap as a key downstream effector of Fat3. Our study uncovers another layer of regulatory mechanisms in controlling the activity of Hippo signaling pathway to regulate the size of neural progenitor pools in the developing spinal cord.

A novel design of a portable funnel light trap (PFLT) was presented for collecting insects in ecological studies. The trap consists of a compact plastic box equipped with a light source and power source, along with two plastic polypropylene interception vanes. The PFLT costs 18.3 USD per unit and weighs approximately 300 g. A maximum of six PFLT units can be packed in one medium-sized backpack (32 cm × 45 cm × 15 cm, 20 L), making it easier to set up multiple units in remote areas wherein biodiversity research is needed. The low cost and weight of the trap also allows for large-scale deployment. The design is customizable and can be easily manufactured to fit various research needs. To validate the PFLT’s efficacy in collecting insects across different habitat types, a series of field experiments were conducted in South Korea and Laos, where 37 trials were carried out. The PFLT successfully collected 7497 insects without experiencing battery issues or damage by rain or wind. Insect compositions and abundances differed across the three sampled habitat types: forests, grasslands, and watersides. This new FLT trap is an important tool for studying and protecting insect biodiversity, particularly in areas wherein conventional light traps cannot be deployed.

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.

Abstract Harrison’s rule, that body size is positively correlated between parasites and hosts, has been reported in a range of taxa, but whether the rule is applicable to cleptoparasitic insects is poorly understood. Subfamily Nomadinae, the largest group of cleptoparasitic bees, usurp the nests of a variety of host bees. Within the subfamily, Nomada exploits the most diverse hosts, using at least ten genera from five families. Here, we reassess the phylogeny of Nomadinae, including the expanded sampling of the genus Nomada, to explore host shift fluctuations throughout their evolutionary history and test the applicability of Harrison’s rule for the subfamily. Our phylogenetic results are mostly congruent with previous investigations, but we infer the tribe Hexepeolini as a sister taxon to the tribe Nomadini. Additionally, the results reveal discrepancies with the traditional classifications of Nomada. Ancestral state reconstruction of host use indicates that, early in their evolution, parasites used closer relatives, before attacking less related groups later. Lastly, we confirm Harrison’s rule in Nomadinae, supporting that body size dynamics influence the host shifts of cleptoparasitic bees.

Abstract Five‐fluorouracil (5‐FU) is a chemotherapeutic agent that is mainly metabolized by the rate‐limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5‐FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into two groups based on DHU/U ratio. The calculated DHU/U ratios ranged from 0.52 to 7.12, and the two groups were classified into the 10th percentile and 90th percentile for untargeted metabolomics analysis using liquid chromatography‐quantitative time‐of‐flight‐mass spectrometry. A total of 4440 compounds were detected and filtered out based on a coefficient of variation below 30%. Our results revealed that six metabolites differed significantly between the high activity group and low activity group (false discovery rate q‐value < 0.05). Uridine was significantly higher in the low DPD activity group and is a precursor of U involved in pyrimidine metabolism; therefore, we speculated that DPD deficiency can influence uridine levels in plasma. Furthermore, the cutoff values for detecting DPD deficient patients from previous studies were unsuitable for Koreans. Our metabolomics approach is the first study that reported the DHU/U ratio distribution in healthy Korean subjects and identified a new biomarker of DPD deficiency.

Abstract 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.

Despite the recent advancement of faunal research of longhorned beetles in South Korea, the number of tribes of Cerambycinae has remained at 16 during the last 40 years.In this paper, two cerambycine tribes, Stenopterini Gistel, 1848 and Thraniini Gahan, 1906, are reported for the first time in Korea by species Merionoeda (Macromolorchus) hirsuta (Mitono & Nishimura, 1936) and Thranius variegatus Bates, 1873, respectively. Morphological comments, biological observations and illustrations of both species are provided. An updated key to tribes of Korean cerambycinae is also provided.

We report from Laos for the first time two genera and three species of lace bugs (Hemiptera, Heteroptera, Tingidae). This brings the number of tingids reported from Laos to 25 genera and 32 species. The two genera are Eritingis Drake & Ruhoff, 1962 and Haedus Distant, 1904, and the three species are Eritingis recentis (Drake & Poor, 1937), Haedus vicarius (Drake, 1927), and Trachypeplus jingae Dang, Guilbert & Bu, 2013.

Abstract Patients with weak or no symptoms accelerate the spread of COVID-19 through various mutations and require more aggressive and active means of validating the COVID-19 infection. More than 30% of patients are reported as asymptomatic infection after the delta mutation spread in Korea. It means that there is a need for a means to more actively and accurately validate the infection of the epidemic via pre-symptomatic detection, besides confirming the infection via the symptoms. Mishara et al. (Nat Biomed Eng 4, 1208–1220, 2020) reported that physiological data collected from smartwatches could be an indicator to suspect COVID-19 infection. It shows that it is possible to identify an abnormal state suspected of COVID-19 by applying an anomaly detection method for the smartwatch’s physiological data and identifying the subject’s abnormal state to be observed. This paper proposes to apply the One Class-Support Vector Machine (OC-SVM) for pre-symptomatic COVID-19 detection. We show that OC-SVM can provide better performance than the Mahalanobis distance-based method used by Mishara et al. (Nat Biomed Eng 4, 1208–1220, 2020) in three aspects: earlier (23.5–40% earlier) and more detection (13.2–19.1% relative better) and fewer false positives. As a result, we could conclude that OC-SVM using Resting Heart Rate (RHR) with 350 and 300 moving average size is the most recommended technique for COVID-19 pre-symptomatic detection based on physiological data from the smartwatch.

Summary: Accurate spatiotemporal control of multicellular self-organization by various signaling pathways is essential for developmental stages. In particular, evolutionarily conserved Wnt signaling serves as a major morphogenetic switch to determine the anteroposterior axis of the embryo. Here, we developed a genetically encoded optochemogenetic Wnt switch, named optochemoWnt, by coupling a blue light-inducible CRY2olig and rapamycin-inducible LRP6c clustering. The rationally designed optochemoWnt successfully modulated Wnt signaling with AND-gated patterns and demonstrated an improved signal-to-noise ratio (SNR). The dual-triggered switch provides a safeguard to prevent signal leakage resulting from ambient light sources under general laboratory conditions. OptochemoWnt expands the molecular toolbox available for the fields of developmental biology and tissue engineering. In addition, the AND-gated strategy of optochemoWnt may be used for other biomedical applications that integrate user defined switch elements with Boolean logic gates.

The UAE's environment is characterized by low rainfall, high temperatures, poor soil and lack of natural waterways. The country has been making tremendous efforts to build a sustainable agricultural and animal wealth sector that is better able to contribute to its national agenda of food security. Commercial cattle farming in such challenging conditions would require an effective disease prediction and warning system for optimizing the production dynamics. Therefore, we are proposing the use of smart livestock system comprising of orally ingested bio-capsules for monitoring the livestock health, connected through a customized long-range network (430 MHz) in the United Arab Emirates, which monitors the real time animal body condition data (temperature and body activity) using a mobile or web-based application. The study demonstrated a 100% success rate in estrus alarms in the test animals, 61.29% for calving alerts and an accurate disease prediction warning in all the animals diagnosed unhealthy. the conception rate in these estrus diagnosed animals with artificial insemination was 61.53%, which was significantly higher than the conception rate in the absence of this detection technology at the farm. The capsule was well tolerated in all the test animals and did not show any acute adverse or allergic reactions. This is the first of its kind of study using these advanced bio-capsules and development of the customized long-range network in the United Arab Emirates for smart livestock healthcare management.

Abstract Reducing the peripheral absolute lymphocyte count (ALC) is a promising therapeutic approach in treating autoimmune diseases. LC51‐0255 is a sphingosine‐1‐phosphate 1 receptor modulator, which is known to decrease the peripheral ALC. We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability profiles of LC51‐0255 after a single oral administration in healthy subjects. A randomized, double‐blind, placebo‐controlled, dose‐escalation study was conducted in 50 healthy subjects. Each subject orally received LC51‐0255 (0.25, 0.5, 1, 2, or 4 mg) or its matching placebo in an 8:2 ratio. Blood and urine samples were collected to assess the PKs, and PDs was evaluated using peripheral ALC and 24‐h hourly heart rate data. Safety and tolerability were assessed by monitoring treatment emergent adverse events (TEAEs), vital signs, 12‐lead electrocardiogram (ECG), continuous 24‐h ECG (via Holter monitoring), clinical laboratory tests, ophthalmologic tests, pulmonary function tests, and physical examinations. A single dose of LC51‐0255 reduced ALC and heart rate in a reversible and dose‐dependent manner. Systemic exposure of LC51‐0255 increased dose‐dependently and its half‐life ranged from 72.2 to 134.0 h. ALC and the systemic exposure of LC51‐0255 seemed to be negatively correlated. LC51‐0255 was well‐tolerated up to 2 mg, and the most common TEAE was bradycardia. The results of this study suggest that LC51‐0255 can be developed into a beneficial treatment option for autoimmune disease.

The Pocadius-complex (Nitidulidae: Nitidulinae) from Korea is reviewed. A total of nine species are recognized, including four new records in Korea: Atarphia cincta Jelínek, Jia & Hájek, 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.

Abstract Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID‐19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m2 and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS‐441524, in patients with COVID‐19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5–10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS‐441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS‐441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID‐19 with renal impairment.

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.

Abstract Baloxavir marboxil, a novel influenza therapeutic agent, is a prodrug rapidly metabolized into its active form, baloxavir acid, which inhibits cap‐dependent endonuclease. This study evaluated the pharmacokinetics (PKs) and safety of baloxavir acid in healthy Korean subjects and compared them with published data in Japanese subjects. This open‐label and single‐ascending dose study was conducted in 30 Korean male subjects, with a single oral dose of baloxavir marboxil (20, 40, or 80 mg) administered to eight subjects each; additionally, 80 mg was administered to six subjects (body weight >80 kg). Noncompartmental and population PK analyses were performed, and results were compared with those of Japanese subjects. Appropriateness of the body weight‐based dosing regimen was evaluated by simulation. PK profiles of baloxavir acid revealed multicompartment behavior with a long half‐life (80.8–98.3 h), demonstrating a dose‐proportional increase. Baloxavir acid reached peak plasma concentration from 3.5 to 4.0 h postdosing. Body weight was identified as a significant covariate of apparent oral clearance and apparent volume of distribution, which was similar to that observed in Japanese subjects. Body weight‐adjusted analysis revealed that exposure to baloxavir acid did not significantly differ between Korean and Japanese subjects. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate. Based on a PK study, clinical data including dosing regimen developed in Japan were adequately extrapolated to Korea, supporting the approval of baloxavir marboxil in Korean as a new treatment option for influenza.

Abstract Cenobamate (XCOPRI and ONTOZRY) is a novel antiseizure medication for the treatment of focal‐onset seizures. Nonetheless, there is limited information on the pharmacokinetics (PKs), safety, and efficacy of cenobamate in Asian people, including Japanese people. This study aimed to evaluate the PKs and safety of cenobamate after a single oral dose in healthy Japanese subjects and to compare the PKs with that reported in non‐Japanese subjects. A randomized, double‐blind, placebo‐controlled, single ascending dose study was conducted at four dose levels of 50, 100, 200, and 400 mg. Subjects were randomly assigned to cenobamate or placebo in a 6:2 ratio. Cenobamate was rapidly absorbed, reaching its maximum plasma concentration (Cmax) in 0.75 to 2.25 h, and was eliminated with a mean half‐life of 37.0 to 57.7 h. The Cmax increased dose proportionally, whereas area under the concentration‐time curve increased more than dose proportionally, which was consistent with the findings in non‐Japanese subjects. The systemic exposure of cenobamate was comparable between Japanese and non‐Japanese subjects at all dose levels evaluated. All adverse events were mild in severity, and their incidence did not show dose‐dependent trends. Furthermore, there were no clinically significant issues in safety parameters, including sedation tests, neurologic examinations, and Columbia Suicide Severity Rating Scale interviews. In conclusion, the systemic exposure of cenobamate after a single dose in Japanese subjects increased by dose, which was similar to the pattern in non‐Japanese subjects. In addition, a single dose of cenobamate was well‐tolerated in the dose range of 50 to 400 mg in healthy Japanese subjects.