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Background Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Abstract The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson’s disease (PD) found in pathological studies is the “rostrocaudal gradient,” which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value

Abstract Our objective was to develop and evaluate the clinical feasibility of deep-learning-based synthetic contrast-enhanced computed tomography (DL-SynCCT) in patients designated for nonenhanced CT (NECT). We proposed a weakly supervised learning with the utilization of virtual non-contrast CT (VNC) for the development of DL-SynCCT. Training and internal validations were performed with 2202 pairs of retrospectively collected contrast-enhanced CT (CECT) images with the corresponding VNC images acquired from dual-energy CT. Clinical validation was performed using an external validation set including 398 patients designated for true nonenhanced CT (NECT), from multiple vendors at three institutes. Detection of lesions was performed by three radiologists with only NECT in the first session and an additionally provided DL-SynCCT in the second session. The mean peak signal-to-noise ratio (PSNR) and structural similarity index map (SSIM) of the DL-SynCCT compared to CECT were 43.25 ± 0.41 and 0.92 ± 0.01, respectively. With DL-SynCCT, the pooled sensitivity for lesion detection (72.0% to 76.4%, P

Abstract Aims/Introduction To investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. Materials and Methods Donor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice. Results In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets. Conclusion The AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.

Abstract Background and Objective This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. Methods A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. Results The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (C max) and area under the curve (AUC) of FDCP to individual tablets were within 0.8–1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. Conclusion This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. Clinical Trial Registration This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Abstract A novel 3D nnU-Net-based of algorithm was developed for fully-automated multi-organ segmentation in abdominal CT, applicable to both non-contrast and post-contrast images. The algorithm was trained using dual-energy CT (DECT)-obtained portal venous phase (PVP) and spatiotemporally-matched virtual non-contrast images, and tested using a single-energy (SE) CT dataset comprising PVP and true non-contrast (TNC) images. The algorithm showed robust accuracy in segmenting the liver, spleen, right kidney (RK), and left kidney (LK), with mean dice similarity coefficients (DSCs) exceeding 0.94 for each organ, regardless of contrast enhancement. However, pancreas segmentation demonstrated slightly lower performance with mean DSCs of around 0.8. In organ volume estimation, the algorithm demonstrated excellent agreement with ground-truth measurements for the liver, spleen, RK, and LK (intraclass correlation coefficients [ICCs] > 0.95); while the pancreas showed good agreements (ICC = 0.792 in SE-PVP, 0.840 in TNC). Accurate volume estimation within a 10% deviation from ground-truth was achieved in over 90% of cases involving the liver, spleen, RK, and LK. These findings indicate the efficacy of our 3D nnU-Net-based algorithm, developed using DECT images, which provides precise segmentation of the liver, spleen, and RK and LK in both non-contrast and post-contrast CT images, enabling reliable organ volumetry, albeit with relatively reduced performance for the pancreas.

Abstract Background Parameters obtained from two‐dimensional (2D) cross‐sectional images have been used to determine body composition. However, data from three‐dimensional (3D) volumetric body images reflect real body composition more accurately and may be better predictors of patient outcomes in cancer. This study aimed to assess the 3D parameters and determine the best predictive factors for patient prognosis. Methods Patients who underwent surgery for colorectal cancer (CRC) between 2010 and 2016 were included in this study. Preoperative computed tomography images were analysed using an automatic segmentation program. Body composition parameters for muscle, muscle adiposity, subcutaneous fat (SF) and abdominal visceral fat (AVF) were assessed using 2D images at the third lumbar (L3) level and 3D images of the abdominal waist (L1–L5). The cut‐off points for each parameter were determined using X‐tile software. A Cox proportional hazards regression model was used to identify the association between the parameters and the treatment outcomes, and the relative influence of each parameter was compared using a gradient boosting model. Results Overall, 499 patients were included in the study. At a median follow‐up of 59 months, higher 3D parameters of the abdominal muscles and SF from the abdominal waist were found to be associated with longer overall survival (OS) and disease‐free survival (all P

We show two experiment setups to verify the applicability of WDM (wavelength division multiplexing)-RoFSO (Radio-over-Free-Space Optics) system: (i) transmission of images files following the data format of IEEE 802.11 wireless local area network; (ii) robust performance analysis of bit error rate for on–off keying signal at a speed of 10 Gbps. Specifically, it is shown that, for 100 m indoor transmission, our testbed satisfies an error-free condition of BER ≤10−12, achieving a total data rate of 20 Gbps. In this paper, we contribute to the evaluation of the practical FSO measurement data by providing experimental measurements.

A sophisticated Bayesian multilevel model for estimating group bias was developed to improve the utility of the ASTM E900-15 embrittlement trend curve (ETC) to assess the conditions of nuclear power plants (NPPs). For multilevel model development, the Baseline 22 surveillance dataset was basically classified into groups based on the NPP name, product form, and notch orientation. By including the notch direction in the grouping criteria, the developed model could account for TTS differences among NPP groups with different notch orientations, which have not been considered in previous ETCs. The parameters of the multilevel model and biases of the NPP groups were calculated using the Markov Chain Monte Carlo method. As the number of data points within a group increased, the group bias approached the mean residual, resulting in reduced credible intervals of the mean, and vice versa. Even when the number of surveillance test data points was less than three, the multilevel model could estimate appropriate biases without overfitting. The model also allowed for a quantitative estimate of the changes in the bias and prediction interval that occurred as a result of adding more surveillance test data. The biases estimated through the multilevel model significantly improved the performance of E900-15.

IntroductionSince the Coronavirus disease 2019 (COVID-19), public safety measures, including social distancing and school closures, have been implemented, precipitating psychological difficulties and heightened online activities for adolescents. However, studies examining the impact of the pandemic on adolescent mental health and their coping strategies in Asian countries are limited. Further, most studies have used survey measures to capture mental health challenges so far. Accordingly, this study aimed to examine the psychological challenges South Korean adolescents experienced and their coping strategies during the pandemic using the Natural Language Processing (NLP) and Text mining (TM) technique on adolescents’ social media texts/posts.MethodsThe data were gathered from social media texts/posts such as online communities, Twitter, and personal blogs from January 1, 2019, to October 31, 2021. The 12,520,250 texts containing keywords related to adolescents’ common psychological difficulties reported during the pandemic, including self-harm, Attention-Deficit/Hyperactivity Disorders (ADHD), and insomnia, were analyzed by TM, NLP using information extraction, co-occurrence and sentiment analysis. The monthly frequency of the keywords and their associated words was also analyzed to understand the time trend.ResultsAdolescents used the word “self-harm” in their social media texts more frequently during the second wave of COVID-19 (August to September 2020). “Friends” was the most associated word with “self-harm.” While the frequency of texts with “Insomnia” stayed constant throughout the pandemic, the word “ADHD” was increasingly mentioned in social media. ADHD and insomnia were most frequently associated with ADHD medications and sleeping pills, respectively. Friends were generally associated with positive words, while parents were associated with negative words.ConclusionDuring COVID-19, Korean adolescents often expressed their psychological challenges on social media platforms. However, their coping strategies seemed less efficient to help with their difficulties, warranting strategies to support them in the prolonged pandemic era. For example, Korean adolescents shared psychological challenges such as self-harm with friends rather than their parents. They considered using medicine (e.g., sleeping pills and ADHD medication) as coping strategies for sleep and attention problems.

BackgroundElectroacupuncture has been used as a treatment; however, a visual bibliometric analysis has not yet been performed in this field. In this study, we aimed to suggest future research topics and directions related to the field by examining the last 20 years of research trends and hotspots of electroacupuncture in stroke.MethodsWe searched the Web of Science database on electroacupuncture as a treatment for stroke published from 2003 to 2022. We analyzed the papers by annual publication, research fields, nations, affiliations, authors, journals, and keywords. VOSviewer software was used to visualize the bibliometric analysis and results. A total of 440 papers were included in the analysis.ResultsThe number of publications has gradually increased every year, and neuroscience has become the most actively studied field. Neural Regeneration Research journal and China had the most publications. Fujian University of Traditional Chinese Medicine, as an affiliated institute, published the most articles. Chen Lidian and Tao Jing presented the largest number of papers, making them the leading contributors in this field. Four clusters were created by analyzing keywords, such as “neuroprotection,” “clinical rehabilitation,” “neuroplasticity,” and “pretreatment-induced tolerance”.ConclusionThis study is the first to analyze the research trends in electroacupuncture as a treatment for stroke using the VOSviewer. It shows the current state of research in the field by visualizing research trends and hotspots. This will help offer reference data for future studies.

This research paper presents the Buckley-James Q-learning (BJ-Q) algorithm, a cutting-edge method designed to optimize personalized treatment strategies, especially in the presence of right censoring. We critically assess the algorithm’s effectiveness in improving patient outcomes and its resilience across various scenarios. Central to our approach is the innovative use of the survival time to impute the reward in Q-learning, employing the Buckley-James method for enhanced accuracy and reliability. Our findings highlight the significant potential of personalized treatment regimens and introduce the BJ-Q learning algorithm as a viable and promising approach. This work marks a substantial advancement in our comprehension of treatment dynamics and offers valuable insights for augmenting patient care in the ever-evolving clinical landscape.

In this research, we investigate the relationship between a movie’s gross and its budget, year of release, season of release, genre, and rating. The movie data used in this research are severely skewed to the right, resulting in the problems of nonlinearity, non-normal distribution, and non-constant variance of the error terms. To overcome these difficulties, we employ a Gaussian copula marginal regression (GCMR) model after adjusting the gross and budget variables for inflation using a consumer price index. An analysis of the data found that year of release, budget, season of release, genre, and rating were all statistically significant predictors of movie gross. Specifically, one unit increases in budget and year were associated with an increase in movie gross. G movies were found to gross more than all other kinds of movies (PG, PG-13, R, and Other). Movies released in the fall were found to gross the least compared to the other three seasons. Finally, action movies were found to gross more than biography, comedy, crime, and other movie genres, but gross less than adventure, animation, drama, fantasy, horror, and mystery movies.

During a severe accident, steam generator (SG) tubes undergo rapid changes in the pressure and temperature. Therefore, an appropriate creep model to predict a short term creep damage is essential. In this paper, a novel creep model for Alloy 690 SG tube material was proposed. It is based on the theta (θ) projection method that can represent all three stages of the creep process. The original θ projection method poses a limitation owing to its inability to represent experimental creep curves for SG tube materials for a large strain rate in the tertiary creep region. Therefore, a new modified θ projection method is proposed; subsequently, a master curve for Alloy 690 SG material is also proposed to optimize the creep model parameters, θi (i = 1–5). To adapt the implicit creep scheme to the finite element code, a partial derivative of incremental creep with respect to the stress is necessary. Accordingly, creep model parameters with a strictly linear relationship with the stress and temperature were proposed. The effectiveness of the model was validated using a commercial finite element analysis software. The creep model can be applied to evaluate the creep rupture behavior of SG tubes in nuclear power plants.

Parkinson’s disease (PD) is a movement disorder that develops due to degenerative loss of dopaminergic cells in the substantia nigra of the midbrain. Recent advances in MRI techniques have demonstrated various imaging findings that can reflect the underlying pathophysiological processes occurring in Parkinson’s disease. Many imaging studies have shown that such findings can assist in the diagnosis of Parkinson’s disease and its differentiation from atypical parkinsonism. In this review, we present MRI techniques that can be used in clinical assessment, such as nigrosome imaging and neuromelanin imaging, and we provide the detailed imaging features of Parkinson’s disease reflecting nigrostriatal degeneration.

For rapid and reliable detection of porcine epidemic diarrhea virus (PEDV) from pig clinical samples, a multiplex, real-time, reverse transcription loop-mediated isothermal amplification (mqRT-LAMP) was developed using two sets of primers and assimilating probes specific to the PEDV N gene and the Sus scrofa β-actin gene, which was used as an endogenous internal positive control (EIPC) to avoid false-negative results. The assay specifically amplified both target genes of PEDV and EIPC in a single reaction without any interference but did not amplify other porcine viral nucleic acids. The limit of detection was 10 copies/μL, 100-fold lower than that of a reverse transcription-polymerase chain reaction (RT-PCR) and equivalent to that of quantitative/real-time RT-PCR (qRT-PCR). This assay has high repeatability and reproducibility with coefficients of variation < 4.0%. The positive signal of the mqRT-LAMP assay was generated within 25 min, demonstrating advantages in rapid detection of PEDV over RT-PCR or qRT-PCR assay, which require at least 2 h turnaround times. In clinical evaluation, the detection rate of PEDV by mqRT-LAMP assay (77.3%) was higher than that of RT-PCR assay (69.7%), and comparable to qRT-PCR (76.8%) with almost 100% concordance (kappa value 0.98). The developed mqRT-LAMP assay can serve as an advanced alternative method for PEDV diagnosis because it has high sensitivity and specificity, rapidity, and reliability even in resource-limited laboratories.

Steam generator (SG) tubes in a nuclear power plant can undergo rapid changes in pressure and temperature during an accident; thus, an accurate model to predict short-term creep damage is essential. The theta (θ) projection method has been widely used for modeling creep-strain behavior under constant stress. However, many creep test data are obtained under constant load, so creep rupture behavior under a constant load cannot be accurately simulated due to the different stress conditions. This paper proposes a novel methodology to obtain the creep curve under constant stress using a modified θ projection method that considers the increase in true stress during creep deformation in a constant-load creep test. The methodology is validated using finite element analysis, and the limitations of the methodology are also discussed. The paper also proposes a creep-strain model for alloy 690 as an SG material and a novel creep hardening rule we call the damage-fraction hardening rule. The creep hardening rule is applied to evaluate the creep rupture behavior of SG tubes. The results of this study show its great potential to evaluate the rupture behavior of an SG tube governed by creep deformation.

Abstract Northeast Asia has been suffering from dramatic increases of particulate matter (PM) since the late 1990s, and it still continues to undergo haze despite various abating regulations. In this study, we investigated aerosol-cloud-precipitation (ACP) interactions with the varied PM, and the impact of long-range transport (LRT) process on ACP in springtime was assessed in Northeast Asia. Our long-term (1995–2019) analysis of PM10 exhibited the correlation with decreases of both sunshine duration and drizzle occurrences that can be interpreted as direct and indirect aerosol effects, while cloud cover induced by the varied PM10 was found only in more than 90% cloud cover (9/10–10/10 category). The online WRF-Chem with wind-blown dust simulation indicated that cloud water was affected by secondary inorganic aerosol (SIA) formation near the surface in upwind areas dominantly, whereas, along the LRT pathway, cloud water perturbation altitudes were increased quasi-linearly toward downward between 1 and 3 km. The gas-to-particle conversion ratios of sulfur ([SO4 2−]/[SO2 + SO4 2−]) and nitrogen ([NO3 −]/[NO2 + NO3 −]) both remain aloft long at the same vertical levels of most perturbed cloud altitude enough to be transported over long distance in springtime. Formations of sulfate and nitrate showed different ACP interaction timing; distinctive shifts in the ratios observed at the exit (Shanghai-Yellow Sea) by nitrate, and entrance areas (Seoul-Tokyo) by sulfate along the LRT pathway, respectively, with higher ratios of 0.8 or more in springtime. Our results indicate that ACP processes have been enhanced at a LRT-related altitude with different SIA production timings that can be considered in species-specific springtime PM abatements over Northeast Asia.

Abstract Background Pulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit. Case presentation A 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50–200 μm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages. Conclusions To the author’s best knowledge, this is the first report of a PVA in a rabbit.

Abstract Background The common marmoset is widely used in current biomedical research for various research fields. We observed macrocytic anemia in a perinatal common marmoset with gradual weight loss and diarrhea. The objective of this case report is to describe the diagnosis and treatment of macrocytic anemia in a perinatal common marmoset. Case presentation A 7-year-old female common marmoset showed clinical signs of gradual weight loss and intermittent diarrhea beginning 3 months after giving birth. Macrocytic anemia was diagnosed due to a decreased red blood cell (RBC) count, low hemoglobin level, and increased mean corpuscular volume (MCV). Multivitamins containing cobalamin and folate were administered for 7 days, and the patient’s RBC count recovered to near the normal range with this treatment. Conclusions Macrocytic anemia can be diagnosed by evaluating the MCV on a complete blood count (CBC) and cobalamin or folate levels and be treated by supplementation with cobalamin and folate. Such supplements may be needed during pregnancy and lactation in female common marmosets and/or in animals with chronic diarrhea.

Radiofrequency (RF) transmit field (B1) mapping is a promising method in mitigating the B1 inhomogeneity in various magnetic resonance imaging (MRI) applications. Although several phase- or magnitude-based B1 mapping methods have been proposed, these methods often require complex modeling, long acquisition time, or specialized MRI sequences. A recently introduced simultaneous echo refocusing (SER) technique can be applied in the B1 mapping method to extend the three-dimensional (3D) spatial coverage only without long data acquisition. Therefore, in this study, a multislice B1 mapping method using composite spin echo sequences and SER techniques is proposed to obtain more accurate B1 mapping with short data acquisition time. To evaluate the performance of the proposed B1 mapping method, computational simulations were performed and compared with Morrell’s method, double angle method, and Yarnykh’s method. These results showed that the angle-to-noise ratio of the proposed B1 mapping method has wider B1 range compared to that of other B1 mapping methods. In addition, the proposed B1 mapping methods were compared to the multislice iterative signal intensity mapping method in both phantom and in vivo human experiments, and there was no remarkable difference between the two methods regarding the flip angle distribution in these experiments. Based on these results, this study demonstrated that the proposed B1 mapping method is suitable for accurately measuring B1 propagation under the condition providing reduced scan time and wider 3D coverage of B1 mapping by applying composite RF pulse and SER techniques into the phase-sensitive method.

In sample surveys, when we need information regarding rare sensitive issues which people often do not prefer to share with others. In such situations this is also awkward for interviewers to ask the direct questions related to confidential and private matters of interviewees. An approach towards the open queries about sensitive issues generally results in the high non-response rates or misleading answers. The aim of this paper is to develop an effective randomized response model to overcome with these types of challenges arising due to sensitive nature of characteristic under study. In this paper we have proposed three-stage randomized response model for estimating mean number of individuals who possessed rare sensitive attribute which makes use of Poisson distribution. The properties of the proposed estimation procedures have been deeply examined when the parameter of a rare unrelated attribute is known as well as unknown. Privacy protection of respondents is also an equally important matter of concern. So measure of privacy protection for the proposed randomized response model has also been examined. Empirical studies are performed to support the theoretical results, which show the dominance of the proposed estimators over well-known contemporary estimators. From the findings of this study we may conclude that proposed randomized response model is rewarding in terms of percent relative efficiencies and privacy protection and may be recommended to survey practitioners for real life applications.

Feline panleukopenia virus (FPV), a member of the species Protoparvovirus carnivoran1, is one of the most fatal pathogens of domestic and wild carnivores. The virus endemically infects domestic carnivores worldwide and its cross-species transmission threatens endangered wild carnivores, including Siberian tigers. In this study, a fatal FPV infection in endangered Siberian tigers was investigated to trace the origin of the virus and elucidate the reason behind FPV’s infection of the vaccinated tigers. Our genetic characterization and phylogenetic analysis revealed that the virus detected in the infected tigers, designated as the KTPV-2305 strain, was closely related to FPV strains circulating in Korean cats, suggesting that it might have been transmitted from stray cats wandering around the zoo. Compared with the prototype FPV reference strains, the KTPV-2305 strain carried three distinct amino acid (aa) mutations in the VP2 protein sequence (I101T, I232V, and L562V) in this study. These three mutations are commonly found in most global FPV strains, including Korean strains, indicating that these mutations are common evolutionary characteristics of currently circulating global FPVs. The reason why the vaccinated tigers were infected with FPV was most likely the insufficient protective immunity of the affected tigress or vaccine failure triggered by the interference of maternal-derived antibodies in the affected tiger cubs. These findings suggest that improved vaccination guidelines are urgently needed to save the lives of wild carnivores from this fatal virus.

The stock index is actively used for the realization of profits using derivatives and via the hedging of assets; hence, the prediction of the index is important for market participants. As market uncertainty has increased during the COVID-19 pandemic and with the rapid development of data engineering, a situation has arisen wherein extensive amounts of information must be processed at finer time intervals. Addressing the prevalent issues of difficulty in handling multivariate high-frequency time-series data owing to multicollinearity, resource problems in computing hardware, and the gradient vanishing problem due to the layer stacking in recurrent neural network (RNN) series, a novel algorithm is developed in this study. For financial market index prediction with these highly complex data, the algorithm combines ResNet and a variable-wise attention mechanism. To verify the superior performance of the proposed model, RNN, long short-term memory, and ResNet18 models were designed and compared with and without the attention mechanism. As per the results, the proposed model demonstrated a suitable synergistic effect with the time-series data and excellent classification performance, in addition to overcoming the data structure constraints that the other models exhibit. Having successfully presented multivariate high-frequency time-series data analysis, this study enables effective investment decision making based on the market signals.

Despite its many advantages, a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay has yet to be developed for canine parainfluenza virus 5 (CPIV5). In this study, a visual RT-LAMP (vRT-LAMP) assay was developed for the rapid detection of CPIV5 in clinical samples. At a constant reaction temperature of 62 °C, the assay was completed within 40 min, and the results could be directly detected with the naked eye using a hydroxynaphthol blue (HNB) metal indicator without any additional detection apparatuses. The assay specifically amplified CPIV5 RNA with a limit of detection of 10 RNA copies/reaction, which was 10-fold more sensitive than the previously reported conventional reverse-transcription polymerase chain reaction (cRT-PCR) assay and was comparable to the previously reported real-time RT-PCR (qRT-PCR) assay. In a clinical evaluation using 267 nasopharyngeal swab samples collected from hospitalized dogs with respiratory symptoms, the CPIV5 detection rate using the vRT-LAMP assay was 5.24% (14/267), which was higher than that of the cRT-PCR assay (4.49%, 12/267) and consistent with that of the qRT-PCR assay, demonstrating 100% concordance with a kappa coefficient value (95% confidence interval) of 1 (1.00–1.00). The discrepancies in the results of the assays were confirmed to be attributed to the low sensitivity of the cRT-PCR assay. Owing to the advantages of a high specificity, rapidity, and simplicity, the developed vRT-LAMP assay using an HNB metal indicator will be a valuable diagnostic tool for the detection of CPIV5 in canine clinical samples, even in resource-limited laboratories.

A new practical modeling of the Norton's power law creep is proposed and implemented to analyze the high temperature behaviors of Alloy 690 SG tube material. In the model, both the stress exponent n and the rate constant B are simply treated as the temperature dependent parameters. Based on the two-step optimization procedure, the temperature function of the rate constant B(T) was determined for the data set of each B value after fixing the stress exponent n value by using the prior optimized function at each temperature. This procedure could significantly reduce the numerical errors when using the power law creep equations. Based on the better description of the steady-state creep rates, the experimental rupture times could also be well predicted by using the Monkman-Grant relationship. Furthermore, the difference in tensile strengths at high temperatures could be very well estimated by assuming the imaginary creep stress related to the given strain rate after correcting the temperature effects on the elastic modulus.

Objective To assess nocturnal hypokinesia using the Korean version of the Nocturnal Hypokinesia Questionnaire (NHQ-K) in Parkinson’s disease (PD) patients across disease stages. Methods We developed the NHQ-K and performed questionnaire-based interviews with 108 PD patients from three referral hospitals. Clinical associations of nocturnal hypokinesia and its impact on health-related quality of life (HRQoL) were also analyzed. Results The NHQ-K showed acceptable internal consistency (0.83) and interrater reliability (0.95). Nocturnal hypokinesia significantly affected HRQoL in PD patients at both the early and advanced stages (adjusted p < 0.001). Increased severity of nocturnal hypokinesia was associated with dyskinesias, off-period disability, apathy, and anxious mood in PD patients (adjusted p < 0.01) after controlling for disease severity and medication dose. Conclusion The NHQ-K is useful for screening nocturnal hypokinesia in PD patients. Given the high impact of nocturnal hypokinesia on HRQoL, comprehensive management of nocturnal disability is needed for PD patients.

Abstract In recent years, minuscule gas bubbles called bulk nanobubbles (BNBs) have drawn increasing attention due to their unique properties and broad applicability in various technological fields, such as biomedical engineering, water treatment, and nanomaterials. However, questions remain regarding the stability and behavior of BNBs. In the present work, BNBs were generated in water using a gas–liquid mixing method. NB analysis was performed using a nanoparticle tracking analysis (NTA) method to investigate the coarsening behavior of BNBs in water over time. The diameters of the BNBs increased, and their cubic radii increased linearly (r3 ~ t) over time. While the concentration of BNBs decreased, the total volume of BNBs remained the same. The size distribution of the BNBs broadened, and the concentration of larger BNBs increased over time. These results indicate that relatively small BNBs disappeared due to dissolution and larger BNBs grew through mass transfer between BNBs instead of coalescence. In other words, BNBs underwent Ostwald ripening: gas molecules from smaller BNBs diffused through the continuous phase to be absorbed into larger BNBs.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aβ)1–42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aβ1–42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aβ1–42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3β, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).

Abstract Background The objective of this study was to investigate whether the use of live attenuated varicella zoster virus (VZV) MAV vaccination can efficiently induce VZV antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (SVV) reactivation in animals immunosuppressed for transplantation studies. Results Clinically available human VZV vaccine was used to induce the production of anti-VZV antibodies in rhesus monkeys. A vial of the vaccine was subcutaneously injected at 0 week, and the second and third vaccination was performed at 5 and 6 weeks by intratracheal inoculation. The titer of anti-VZV IgG was assessed at 0, 2, 4, 6, and 7 weeks. At 2 weeks, 3/16 were seropositive for VZV IgG. At 6 weeks, 9/16 were shown to be seropositive. At 7 weeks, 16/16 were found to be seropositive. Conclusions The VZV vaccine via intratrachael inoculation was shown to induce VZV IgG humoral immunity in rhesus monkeys and may be important immunosuppressed macaques for transplantation studies. Although the humoral immunity produced is an important finding, further studies will be necessary to confirm possible protection and it could protect probably against SVV infection in rhesus monkey.

BackgroundThe glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.MethodsWe searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.ResultsAccording to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.ConclusionWe may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.

Abstract Background Ankylosis in the temporomandibular joint (TMJ) is known to have various etiologies in veterinary medicine. We observed a case of fibrous ankylosis of the TMJ in a newly imported rhesus monkey (Macaca mulatta). Case presentation Moderate to severe attrition was found in the middle labial portion of the left maxillary canine. No tenderness around the jaw was detected in the physical examination. The WBC count, CRP level, rheumatoid factor level, and other parameters were normal. Irregularity in the joint surface was observed in both TMJs in the radiographic and computed tomographic examinations, but the left TMJ presented more severe irregularity. It was determined that the removal of the locked portion of the left canine would alleviate the case of lockjaw and allow intubation with an endotracheal tube. Canine tooth crown reduction was performed for both canine teeth. The mouth opening distance slightly (approximately 5 mm) increased up to 20 mm. We concluded that the attrition of canine teeth was not the reason for lockjaw and ankyloses originating from TMJ disease. Fibrotic synovial tissue and joint surface irregularity were observed by necropsy. The presence of fibrocartilage in most areas of the TMJ was confirmed by histology. The diagnosis was fibrous ankylosis of the TMJ associated with DJD. Conclusions To the best of our knowledge, this is the first report of degenerative joint disease of the TMJ in a rhesus monkey with fibrous ankylosis of the TMJ.

Abstract Background The reduction of canine teeth in adult males in whom permanent canine teeth eruption occurs should be considered due to the safety of humans or other monkeys. The objective of this study was to evaluate the complications of canine teeth reduction in macaques. Case presentation: Canine teeth reductions were performed in 8 rhesus and 2 cynomolgus macaques. Complications related to canine teeth reduction were evaluated at one to three week intervals during the experimental period by gross examination, CBC, and monitoring of appetite. One monkey showed a fistula due to periapical abscess and neutrophilia more than 2 years after canine teeth reduction, and extraction of the diseased canine tooth was performed; the other 9 monkeys showed no complications during the observation period. This report shows the effectiveness of canine teeth reduction with few complications. Conclusion Canine teeth reduction in male macaques is an acceptable procedure for reducing the severity of injury to humans or other monkeys.

While many infectious disorders are unknown to most neurologists, COVID-19 is very different. It has impacted neurologists and other health care workers, not only in our professional lives but also through the fear and panic within our own families, colleagues, patients and their families, and even in the wider public. COVID-19 affects all sorts of individuals, but the elderly with underlying chronic conditions are particularly at risk of severe disease, or even death. Parkinson’s disease (PD) shares a common profile as an age-dependent degenerative disorder, frequently associated with comorbidities, particularly cardiovascular diseases, so PD patients will almost certainly fall into the high-risk group. Therefore, the aim of this review is to explore the risk of COVID-19 in PD based on the susceptibility to severe disease, its impact on PD disease severity, potential long-term sequelae, and difficulties of PD management during this outbreak, where neurologists face various challenges on how we can maintain effective care for PD patients without exposing them, or ourselves, to the risk of infection. It is less than six months since the identification of the original COVID-19 case on New Year’s Eve 2019, so it is still too early to fully understand the natural history of COVID-19 and the evidence on COVID-19-related PD is scant. Though the possibilities presented are speculative, they are theory-based, and supported by prior evidence from other neurotrophic viruses closely related to SARS-CoV-2. Neurologists should be on high alert and vigilant for potential acute and chronic complications when encountering PD patients who are suspected of having COVID-19.

Abstract Purpose The aim of this study was to compare the discrepancy of alignment categorization in total knee arthroplasty (TKA) between the anatomical femorotibial angle (aFTA) measured on short knee radiographs and the mechanical hip–knee–ankle axis angle (mHKA) measured on full-length radiographs in knees with and without bowing. Methods From January 2014 to June 2017, 107 of 526 osteoarthritic knees at our hospital were found to have femoral or tibial bowing. Bowing was defined as a femoral bowing angle (FBA) > 3° or 2° or 7°, mHKA> 3°) alignments. We compared the categorization of alignments between knees with and without bowing using the McNemar test and used logistic regression to find factors for the alignment discordance. Results Coronal alignment was discordant in 26.2% of the knees with bowing and 13.1% of the knees without bowing (p

Purpose Head rotation is thought to have an effect on obstructive sleep apnea (OSA) severity. However, keeping the head rotated fully during sleep is difficult to maintain, and the effect of head rotation is not the same in all OSA patients. Thus, this study aimed to identify whether less head rotation has an effect on airway patency and determine the responder characteristics to the head rotation maneuver (HRM). Methods We recruited 221 patients who underwent overnight polysomnography and drug-induced sleep endoscopy (DISE) in a tertiary hospital from June 2019 to July 2020. Airway patency and the site of airway collapse were determined in the supine position with the head at 0, 30, and 60 degrees of rotation (HRM0°, HRM30°, and HRM60°, respectively) during DISE. The site of collapse was determined using the VOTE classification system: the velum (palate), oropharyngeal lateral walls, tongue base, and epiglottis. Each structure was labeled as 0, 1, or 2 (patent, partially obstructed, and completely obstructed, respectively). Airway response to the HRM30° and 60° and the clinical characteristics associated with airway opening were analyzed. Results The study population had a median age of 52 (25–61) years, a body mass index of 26.7(24.6–29.4) kg/m2, and the apnea-hypopnea index (AHI) of 28.2(13.7–71.9) events/h. HRM influenced airway patency positively not only with HRM60° (pConclusion Head rotation improved airway obstruction in OSA patients, even with a small degree of rotation, and should be further explored as a potential form of therapy in appropriately selected patients.

Regional accuracy was examined using extreme gradient boosting (XGBoost) to improve frost prediction accuracy, and accuracy differences by region were found. When the points were divided into two groups with weather variables, Group 1 had a coastal climate with a high minimum temperature, humidity, and wind speed and Group 2 exhibited relatively inland climate characteristics. We calculated the accuracy in the two groups and found that the precision and recall scores in coastal areas (Group 1) were significantly lower than those in the inland areas (Group 2). Geographic elements (distance from the nearest coast and height) were added as variables to improve accuracy. In addition, considering the continuity of frost occurrence, the method of reflecting the frost occurrence of the previous day as a variable and the synthetic minority oversampling technique (SMOTE) pretreatment were used to increase the learning ability.

This study was performed to investigate the improving effect of a mixture of Artemisia argyi and Saururus chinensis (AASC) on cognitive dysfunction in mice with long-term exposure to fine particles (particulate matter smaller than 2.5 µm: PM2.5). The main compounds of AASC were identified as dicaffeoylquinic acid isomers of A. argyi and a quercetin-3-glucoside of S. chinesis. As a result of behavioral tests for the evaluation of cognitive function, it was confirmed that cognitive dysfunction was induced in the PM2.5 exposure group, and a tendency to improve in the AASC group was confirmed. Increased oxidative stress and inflammatory response and mitochondrial dysfunction were observed in the brain and lung tissues of the PM group. Damage to the brain and lung affected the accumulation of amyloid beta (Aβ) in the brain. It increased Aβ and induced the cholinergic dysfunction, hyperphosphorylation of the tau protein, and activation of apoptosis, leading to cognitive impairment. However, AASC suppressed brain and lung oxidative stress and inflammation, thereby suppressing brain Aβ expression. Consequently, this study shows the potential that a steady intake of plant resources with antioxidant and anti-inflammatory activity could prevent cognitive impairment caused by PM2.5.

This paper proposes a nonparametric directional dependence by using the local polynomial regression technique. With data generated from a bivariate copula having a nonmonotone regression structure, we show that our nonparametric directional dependence is superior to the copula directional dependence method in terms of the root-mean-square error. To validate the directional dependence with real data, we use the log returns of daily prices of Bitcoin, Ethereum, Ripple, and Stellar. We conclude that our nonparametric directional dependence, by using the local polynomial regression technique with asymmetric-threshold GARCH models for marginal distributions, detects the directional dependence better than the copula directional dependence method by an asymmetric GARCH model.

Higher risk of major hemorrhage associated with concomitant use of dabigatran and simvastatin compared to other statins was previously reported with a suggestion of P-glycoprotein-mediated interaction. The aim of this study was to evaluate the effects of simvastatin on pharmacokinetics and anticoagulant effects of dabigatran, a direct oral anticoagulant. A total of 12 healthy subjects were enrolled in an open-label, two-period, single sequence study. Subjects were given 150 mg of dabigatran etexilate followed by 40 mg of once-daily simvastatin for seven days. Dabigatran etexilate was administered with simvastatin on the seventh day of simvastatin administration. Blood samples for pharmacokinetic and pharmacodynamic analyses were obtained until 24 h post-dose of dabigatran etexilate with or without co-administration of simvastatin. Pharmacokinetic parameters were derived from noncompartmental analysis for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide. When simvastatin was co-administered, geometric mean ratios of area under time-concentration curves for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide were 1.47, 1.21, and 1.57, respectively, compared to when dabigatran etexilate was administered alone. Thrombin generation assay and coagulation assay showed similar profiles between before and after co-administration of simvastatin. This study provides evidence that simvastatin treatment plays a minor role in modulating pharmacokinetics and anticoagulant effects of dabigatran etexilate.

Two species of porcine parainfluenza viruses (PPIV), PPIV1 and PPIV5, are globally distributed in pig herds and associated with porcine respiratory diseases, and a diagnostic tool for the simultaneous detection of the two viruses is required. In this study, a TaqMan probe-based duplex real-time reverse transcription polymerase chain reaction (dqRT-PCR) assay was first developed for the differential detection of PPIV1 and PPIV5 nucleocapsid protein (NP) genes in porcine clinical samples. The dqRT-PCR assay was highly sensitive, its limit of detection was approximately 10 RNA copies/reaction, it specifically amplified the targeted NP genes of PPIV1 and PPIV5 without cross-reacting with other porcine pathogens, and their clinical detection rates were 15.2% and 0.7%, respectively. The results from 441 clinical samples taken from 278 Korean domestic pig farms showed that the prevalence of PPIV1 and PPIV5 was 11.2% and 1.1%, respectively, and co-infection of both viruses was confirmed in a farm, suggesting that PPIV1 and PPIV5 are co-circulating in current Korean pig herds. Phylogenetic analysis based on the partial NP genes suggested that genetically diverse PPIV1 strains are circulating in Korean pig herds. The developed dqRT-PCR assay was found to be an accurate, reliable, and quantitative detection tool for PPIV1 and PPIV5 RNA in clinical pig samples and will be useful for etiological and epidemiological studies and the control of viral infections in the field.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been frequently reported in companion dogs and cats worldwide during the ongoing coronavirus disease. However, RT-qPCR methods developed for humans have been used for the diagnosis of SARS-CoV-2 infections in suspected companion dogs and cats owing to the lack of the companion animal-tailored methods. Therefore, we developed a multiplex RT-qPCR (mRT-qPCR) using newly designed primers and probes targeting RdRp and N genes of all currently circulating SARS-CoV-2 variants as well as the canine or feline 16S rRNA gene as an endogenous internal positive control (EIPC) for reliable diagnosis of SARS-CoV-2 infection from suspected dogs and cats. The developed mRT-qPCR assay specifically detected the target genes of SARS-CoV-2 but no other canine or feline pathogens. Furthermore, canine and feline EIPCs were stably amplified by mRT-qPCR in samples containing canine- or feline-origin cellular materials. This assay has high repeatability and reproducibility, with an optimal limit of detection (

Vertical mixing in the planetary boundary layer (PBL) is an important factor in the prediction of particulate matter (PM) concentrations; however, PBL height (PBLH) in the stable atmosphere remains poorly understood. In particular, the assessment of uncertainties related to nocturnal PBLH (nPBLH) is challenging due to the absence of stable atmosphere observations. In this study, we explored nPBLH–PM2.5 interactions by comparing model results and observations during the Korea–United States Air Quality Study (KORUS-AQ) campaign (1–31 May 2016). Remote sensing measurements (e.g., aerosol and wind Doppler lidar) and on-line WRF-Chem modeling results were used by applying three different PBL parameterizations: Yonsei University (YSU), Mellor–Yamada–Janjic (MYJ), and Asymmetrical Convective Model v2 (ACM2). Our results indicated that the uncertainties of PBLH–PM interactions were not large in daytime, whereas the uncertainties of nPBLH–PM2.5 interactions were significant. All WRF-Chem experiments showed a clear tendency to underestimate nighttime nPBLH by a factor of ~3 compared with observations, and shallow nPBLH clearly led to extremely high PM2.5 peaks during the night. These uncertainties associated with nPBLH and nPBLH–PM2.5 simulations suggest that PM2.5 peaks predicted from nighttime or next-morning nPBLH simulations should be interpreted with caution. Additionally, we discuss uncertainties among PBL parameterization schemes in relation to PM2.5 simulations.

This study aimed to evaluate whether the single nucleotide polymorphisms of ATP-binding cassette subfamily G member 2 (ABCG2) and solute carrier family 2 member 9 (SLC2A9) affect individual blood uric acid levels using pyrosequencing. ABCG2 (rs2231142, rs72552713, rs2231137), SLC2A9 (rs3734553, rs3733591, rs16890979), and individual uric acid levels were prospectively analyzed in 250 healthy young Korean male participants. Prominent differences in uric acid levels of the alleles were observed in the SLC2A9 rs3733591 polymorphism: wild-type (AA) vs. heterozygote (AG), 0.7 mg/dL (p < 0.0001); AA vs. mutant type (GG), 1.32 mg/dL (p < 0.0001); and AG vs. GG, 0.62 mg/dL (p < 0.01). In ABCG2 single nucleotide polymorphisms (SNPs), the statistically significant differences in uric acid levels were only found in rs2231142 between CC vs. AA (1.06 mg/dL; p < 0.001), and CC vs. CA (0.59 mg/dL; p < 0.01). Serum uric acid levels based on the ABCG2 and SLC2A9 diplotype groups were also compared. The uric acid levels were the lowest in the CC/AA diplotype and highest in the AA/AG diplotype. In addition, the SNP SLC2A9 rs3733591 tended to increase the uric acid levels when the ABCG2 rs2231142 haplotypes were fixed. In conclusion, both the ABCG2 rs2231142 and SLC2A9 rs3733591 polymorphisms may additively elevate blood uric acid levels.

This paper shows a visual analysis and the dependence relationships of COVID-19 mortality data in 50 states plus Washington, D.C., from January 2020 to 1 September 2022. Since the mortality data are severely skewed and highly dispersed, a traditional linear model is not suitable for the data. As such, we use a Gaussian copula marginal regression (GCMR) model and vine copula-based quantile regression to analyze the COVID-19 mortality data. For a visual analysis of the COVID-19 mortality data, a functional principal component analysis (FPCA), graphical model, and copula dynamic conditional correlation (copula-DCC) are applied. The visual from the graphical model shows five COVID-19 mortality equivalence groups in the US, and the results of the FPCA visualize the COVID-19 daily mortality time trends for 50 states plus Washington, D.C. The GCMR model investigates the COVID-19 daily mortality relationship between four major states and the rest of the states in the US. The copula-DCC models investigate the time-trend dependence relationship between the COVID-19 daily mortality data of four major states.

Teneligliptin, a dipeptidyl peptidase-4 inhibitor, is used to treat type 2 diabetes mellitus. FMO3 and CYP3A4 metabolize teneligliptin into teneligliptin sulfoxide. This study examined the effects of FMO3 (rs909530, rs1800822, rs2266780, and rs2266782) and CYP3A4 (rs2242480) polymorphisms on teneligliptin pharmacokinetics at a steady state among 23 healthy participants administered 20 mg teneligliptin daily for 6 days. Subjects with FMO3 rs909530, rs2266780, and rs2266782 polymorphisms exhibited a significant gene dosage-dependent increase in maximum steady-state plasma drug concentration (Cmax,ss) and area under the drug concentration vs time curve (AUC) (p

Cryptocurrencies are highly volatile investment assets and are difficult to predict. In this study, various cryptocurrency data are used as features to predict the log-return price of major cryptocurrencies. The original contribution of this study is the selection of the most influential major features for each cryptocurrency using the volatility features of cryptocurrency, derived from the autoregressive conditional heteroskedasticity (ARCH) and generalized autoregressive conditional heteroskedasticity (GARCH) models, along with the closing price of the cryptocurrency. In addition, we sought to predict the log-return price of cryptocurrencies by implementing various types of time-series model. Based on the selected major features, the log-return price of cryptocurrency was predicted through the autoregressive integrated moving average (ARIMA) time-series prediction model and the artificial neural network-based time-series prediction model. As a result of log-return price prediction, the neural-network-based time-series prediction models showed superior predictive power compared to the traditional time-series prediction model.

This paper introduces methodologies in forecasting oil prices (Brent and WTI) with multivariate time series of major S&P 500 stock prices using Gaussian process modeling, deep learning, and vine copula regression. We also apply Bayesian variable selection and nonlinear principal component analysis (NLPCA) for data dimension reduction. With a reduced number of important covariates, we also forecast oil prices (Brent and WTI) with multivariate time series of major S&P 500 stock prices using Gaussian process modeling, deep learning, and vine copula regression. To apply real data to the proposed methods, we select monthly log returns of 2 oil prices and 74 large-cap, major S&P 500 stock prices across the period of February 2001–October 2019. We conclude that vine copula regression with NLPCA is superior overall to other proposed methods in terms of the measures of prediction errors.

There is a large variability in individual responses to atorvastatin administration. This study assessed the pharmacogenetic effects of solute carrier organic anion transporter family member 1B1 (SLCO1B1, c.388A>G and c.521T>C) and cytochrome P450 3A5 (CYP3A5, CYP3A5*3) genetic polymorphisms on the pharmacokinetics of atorvastatin and its active metabolite, 2-hydroxy (2-OH) atorvastatin, in 46 individuals who were administered a clinically used single oral dosage of 80 mg. The Cmax and AUC of atorvastatin in CYP3A5*3/*3 carriers were 2.6- and 2.8-fold higher, respectively, than those in CYP3A5*1/*1 carriers, and similar results were observed for 2-OH atorvastatin pharmacokinetics. SLCO1B1 c.521T>C also increased the AUC of atorvastatin and 2-OH atorvastatin. The AUC ratio of atorvastatin and 2-OH atorvastatin were not affected by SLCO1B1 c.388A>G or c.521T>C, whereas CYP3A5*3 reduced the AUC ratio. In an analysis evaluating the simultaneous effect of the SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms, SLCO1B1 c.521TT/CYP3A5*1/*1 carriers showed lower Cmax and AUC values for atorvastatin and 2-OH atorvastatin than in individuals with the SLCO1B1 c.521T>C and/or CYP3A5*3 genotypes. Among the participants with the SLCO1B1 c.521TT genotype, the CYP3A5*3 carriers had a higher systemic exposure to atorvastatin and 2-OH atorvastatin than the CYP3A5*1/*1 carriers. Thus, SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms affect the pharmacokinetics of atorvastatin and 2-OH atorvastatin.

Imatinib is transported extracellularly by ABCB1 and ABCG2 efflux transporters and bound to alpha-1-acid glycoprotein (AGP) in the bloodstream. However, the clinical and pharmacokinetic effects of ABCB1 and ABCG2 on imatinib were inconsistent in the previous literature and have not been confirmed. Therefore, in the present study, we explored the effects of the ABCG2 and ABCB1 genetic polymorphisms on imatinib pharmacokinetics in association with plasma AGP levels in healthy subjects. Twenty-seven healthy individuals were recruited, genotyped for ABCG2 and ABCB1, and given a single oral dose of 400 mg imatinib. Plasma imatinib concentrations were measured and its pharmacokinetics was assessed with respect to ABCG2 (c.421C>A and c.34G>A) and ABCB1 (c.1236C>T, c.2677C>T/A, and c.3435C>T) genotypes, and plasma AGP levels. AGP levels showed a strong positive correlation with imatinib pharmacokinetics. ABCG2 c.421C>A single nucleotide polymorphism showed a statistically significant effect on imatinib pharmacokinetics in low plasma AGP levels groups (