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Background The United States requires a patent linkage system in other countries as part of free trade agreements. However, introducing a patent linkage system could be a significant barrier to the timely approval of generic drugs. This study aimed to evaluate the perceived impact of the patent linkage system in South Korea held by domestic manufacturers and analyze variations in evaluating the system according to the characteristics of domestic manufacturers. Methods In 2020, we conducted a questionnaire survey of 39 domestic manufacturers. The survey consisted of perceptions of the system, factors affecting patent challenges, and the perceived impact of the system. A 5-point Likert scale was used to rate each item. Domestic manufacturers were categorized into three groups based on their experience of listing a patent and acquiring first generic exclusivity. Results More than half of the manufacturers surveyed had experience of listing a patent. The patent linkage system could protect the involved patents. However, manufacturers perceived that they could successfully challenge the validity of the involved patents and then obtained market approval for generic drugs. Manufacturers responded that market size, expectations for succeeding in litigation, and expectations for manufacturing the drug were the most relevant factors when they initiated patent challenges. Manufacturers reported that the system, in particular the first generic exclusivity, enhanced the research and development capability of generic manufacturers, increased their domestic sales, and improved access to generic drugs. Conclusions The perceived impact of the patent linkage system was limited to the domestic market and generic drugs. In narrowing the impact to the effects on the domestic industry, the system had positive impacts of the system on generic manufacturers. The first generic drug exclusivity lies at the center of this positive perception. However, manufacturers perceived that the current system did not provide enough incentives for domestic manufacturers to be granted first generic drug exclusivity through patent challenges.

A novel device structure for thermally activated delayed fluorescence (TADF) top emission organic light-emitting diodes (TEOLEDs) that improves the viewing angle characteristics and reduces the efficiency roll-off is presented. Furthermore, we describe the design and fabrication of a cavity-suppressing electrode (CSE), Ag (12 nm)/WO3 (65 nm)/Ag (12 nm) that can be used as a transparent cathode. While the TADF-TEOLED fabricated using the CSE exhibits higher external quantum efficiency (EQE) and improved angular dependency than the device fabricated using the microcavity-based Ag electrode, it suffers from low color purity and severe efficiency roll-off. These drawbacks can be reduced by using an optimized multi-quantum well emissive layer (MQW EML). The CSE-based TADF-TEOLED with an MQW EML fabricated herein exhibits a high EQE (18.05%), high color purity (full width at half maximum ~ 59 nm), reduced efficiency roll-off (~ 46% at 1000 cd m−2), and low angular dependence. These improvements can be attributed to the synergistic effect of the CSE and MQW EML. An optimized transparent CSE improves charge injection and light outcoupling with low angular dependence, and the MQW EML effectively confines charges and excitons, thereby improving the color purity and EQE significantly. The proposed approach facilitates the optimization of multiple output characteristics of TEOLEDs for future display applications.

Tenebrio molitor larva (mealworms) has recently attracted attention as a protein source for food and feed. The larva is generally fed with wheat bran, which can be possibly contaminated with glyphosate. To establish food safe standards, a rugged and effective analytical method for glyphosate, aminomethylphosphonic acid, glufosinate, and their metabolites including 3-methylphosphinico-propionic acid, and N-acetyl glufosinate, in mealworms was optimized using liquid chromatography tandem mass spectrometry. An anionic polar pesticide column was used due to its high suitability for glyphosate. Acidified water and acetonitrile were used to extract the target compounds without contribution from various fatty and pigment interferences derived from brownish insects. Seven different clean-up procedures ((1) 50 mg C18 (2) 20 mg C18/Z-sep (3) PRiME hydrophilic-lipophilic balance (HLB) cartridge (4) 75 mg Z-sep, (5) 75 mg Z-sep+, (6) EMR-lipid cartridge, and (7) 50 mg ENVI-Carb) were compared. Due to its simplicity and cost-effectiveness, PRiME HLB was selected for clean-up. The recoveries of the target compounds were ranged from 86 to 96% with

Delirium is a common neurocognitive complication in cancer. Despite this, the studies examining the trajectory of the severity of delirium symptoms and its impact on health outcome in gastric cancer is rather limited. This study examined the trajectory of delirium symptom severity (DSS) following resection surgery for gastric cancer and its prospective association with cognitive function. A three-wave prospective observational study was conducted with 242 gastric cancer patients admitted for resection surgery at a teaching hospital in South Korea from May 2016 to November 2017. DSS was assessed by the clinical staff before and 1, 2, 3, and 7 days after surgery using the Delirium Rating Scale-Revised-98. A survey including the Functional Assessment of Cancer Therapy-Cognitive Scale (FACT-Cog) and Mini-Mental State Examination (MMSE) was administered before surgery (T0), 7 days after (T1), and 3 to 6 months after surgery (T2). Out of 242 participants, 48.8% (118) completed the survey at all three time points, 43.4% (105) did so for two time points, and 7.9% (19) for one time point. No cases of full delirium were observed over four postoperative time points. Latent growth curve modeling analyses indicated that DSS declined over 3 days after surgery. Age and anesthesia time were positively associated with the initial level of DSS. A medication history for memory complaints was related to a slower recovery from delirium symptoms. While the use of propofol as an anesthetic agent was associated with lower initial DSS, it predicted a slower recovery from DSS. A higher initial DSS predicted a lower T1 MMSE score. Severity of postoperative delirium symptoms predicts a short-term and objective cognitive function post-surgery. Monitoring and timely treatment of postoperative delirium symptoms is needed to diminish cognitive consequences in gastric cancer patients.

Background Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. Methods We conducted a retrospective cohort study using Korea’s National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. Results During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p Conclusions Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer.

Previous studies have revealed the negative consequences of shift work in some individuals, with others better tolerating shift work. The present study investigated clinical implications of shift work-related sleep complaints as a manifestation of shift-work intolerance. Responses were obtained from 923 shift workers and 850 non-shift workers at Seoul National University Bundang Hospital in Seongnam, Korea. The self-reported questionnaires were administered to assess demographic and clinical factors of the participants. Shift work-related sleep complaints were defined as complaints of insomnia or excessive sleepiness related to shift work schedule. Shift workers with sleep complaints suffered from more severe fatigue, depression, anxiety and impaired quality of life compared with both non-shift workers and shift workers without sleep complaints (all p

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p

This study established a hydrological drought forecasting system based on the Bayesian method and evaluated its utilization for South Korea. The regression result between Historical Runoff (HR) and Ensemble Streamflow Prediction Runoff (ESP_R) was used as prior information in the Bayesian method. Additionally Global seasonal forecast System 5 Runoff (GS5_R) produced using a dynamic prediction method was used in a likelihood function. Bayesian Runoff (BAY_R), as posterior information, was generated and compared with the ESP_R and GS5_R results for predictive ability evaluation. The Standardized Runoff Index (SRI) was selected for the drought prediction, and the BAY_SRI, GS5_SRI and ESP_SRI were computed using BAY_R, GS5_R and ESP_R, respectively. The Correlation Coefficient (CC), Nash-Sutcliffe Efficiency (NSE) and Receiver Operating Characteristic (ROC) score of BAY_SRI were the highest, and the Root Mean Square Error (RMSE) of BAY_SRI was the lowest among the methods. The Bayesian method improved the behavioral and quantitative error of drought prediction and the predictive ability of the occurrence of drought. In particular, the simulation accuracy was significantly improved during the flood season. Additionally, BAY_SRI represented past drought scenarios better than did the other two methods. Overall, we found that the Bayesian method could be applied for hydrological drought predictions for based on 1- and 2-month lead times.

Metal-enhanced fluorescence (MEF) of quantum dots (QDs) and its potential application in microarray-based immunoassays was investigated using silver nanoparticles (AgNPs) prepared by the in situ photoreduction of Ag+ inside a multilayer film consisting of poly(ethyleneimine) (PEI) and hyaluronic acid (HA). UV–Vis spectroscopy, X-ray diffraction, atomic force microscopy, scanning electron microscopy, and transmission electron microscopy confirmed the formation of well-dispersed AgNPs within the multilayer films, the thickness and the amount of which depended on the number of HA layers. Using AgNPs-containing hybrid multilayered films, it was possible to observe the MEF effect of adsorbed QDs, which could be tuned by the thickness of interlayer spacer film prepared of the layer-by-layer assembly of PEI and poly(styrene sulfonate). When the MEF-inducing hybrid film was used as a platform for immunoassay, a significant improvement in the fluorescence signal and sensitivity of the biosensing were observed in the presence of AgNPs in comparison with films that did not contain the nanoparticles.

Association of official agricultural chemists official method was adapted and used to develop analytical method for determination of 76 pesticides residues in persimmon, grape, and pear by concurrent use of liquid chromatography-tandem mass spectrometry. Despite few exceptions in particular matrix, two fortified spiking (100 and 400 ppb) in three matrices gave satisfactory results in terms of accuracy, repeatability, precision, and linearity. Method detection limits (MDLs) were determined using five low spiking and eight replicate samples. MDLs were calculated by multiplying the standard deviation with student t-value 2.998 for n-1 (7) degree of freedom at 99% confident level. limit of quantification were obtained by multiplying standard deviation with 10. Experimental results indicate grape was the most problematic matrix among tested fruits and persimmon the least. Etoxazole is the most problematic pesticide and not applicable in this method. Developed method was successfully applied for the determination of residual pesticides in blindincurred samples.

This study examined the degradation of the device performance of InGaZnO4 (IGZO)-based thin-film transistors after annealing at high temperatures in air ambient. Using various characterization methods including scanning electron microscopy, x-ray diffraction, and transmission electron microscopy, we were able to disclose the details of a two-stage phase transformation that led to the device performance degradation. The Mo electrodes first succumbed to oxidation at moderate temperatures (400∼500 °C) and then the Mo oxide further reacted with IGZO to produce an In–Mo–O compound with some Ga at higher temperatures (600∼700 °C). We analyzed our results based on the thermodynamics and kinetics data available in the literature and confirmed that our findings are in agreement with the experimental results.

【The purpose of this study was to compare the efficacy of Lorelin Depot $Injection^{(R)}$ (Dongkook Pharm. Co., LTD) with Lucrin Depot $Injection^{(R)}$ (Abbott) by measuring serum testosterone level in rats. Leuprorelin (leuprolide acetate), which is an active compound for the two formulations, is an LHRH analogue that is used for the treatment of a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. Lorelin Depot $Injection^{(R)}$ is a micro-encapsulated formulation to suppress testosterone level by releasing leuprorelin continuously for four weeks with a single subcutaneous injection. The comparison study of the efficacy was performed during four weeks, and serum testosterone levels were monitored in the two formulations. The mean serum testosterone levels from the formulations were decreased to that of the castrate range (50 ng/dL or less) after three days after the initial depot injection, and the concentration were remained throughout four weeks' period. There were no significant differences in the $AUC_{0-3day}$ of testosterone and testosterone levels at 3, 7, 14, 21 and 28 days between the two formulations. These results indicate that the two formulations, Lorelin Depot $Injection^{(R)}$ and Lucrin Depot $Injection^{(R)}$ , are bioequivalent in terms of the serum testosterone level in rats.】

Imidazolium iodides (Im+I−s) were synthesized with different substituents of the cation and used as electrolytes in dye-sensitized solar cells (DSSCs), and the effects of such substituents were investigated in terms of the photovoltaic performance of the cells. Synthesized iodides were verified by 1H-NMR. Among the iodides, 1,3-diethylimidazolium iodide enabled a solar energy conversion efficiency of 4.8% for its DSSC, while 1-(4-acetophenyl)-3-ethylimidazolium iodide rendered an efficiency of 3.1% for its cell. In all cases the short-circuit photocurrent (J sc) was found to increase with decrease in size of the substituent, which was also verified to be valid in the case of a quasi-solid state DSSC. Results are explained by the electrostatic interactions between solvated Im+ and negatively charged species based on the correlation between diffusion coefficients of I− and I 3 − and J sc values. These explanations are supported by steady-state voltammetry and electrochemical impedance spectroscopy (EIS).

The ethanol extract of the peony root (Paeonia Lactiflora Pall, Paeoniaceae) as well as its major active components including gallic acid and methyl gallate were evaluated for their protective effects against free radical generation and lipid peroxidation. In addition, the protective effects against hydrogen peroxide-induced oxidative DNA damage in a mammalian cell line were examined. The ethanol extracts of the peony root (PREs) and its active constituents, gallic acid and methyl gallate, exhibited a significant free radical scavenging effect against 1,1-diphenyl-2-picryl hydrazine (DPPH) radical generation and had an inhibitory effect on lipid peroxidation, as measured by the level of malondialdehyde (MDA) formation. The PREs did not have any pro-oxidant effect. They strongly inhibited the hydrogen peroxide-induced DNA damage from NIH/3T3 fibroblasts, as assessed by single cell gel electrophoresis. Furthermore, the oral administration of 50% PRE (50% ethanol extract of peony root), gallic acid and methyl gallate potently inhibited the formation of micronucleated reticulocytes (MNRET) in the mouse peripheral blood induced by a KBrO3 treatment in vivo. Therefore, PREs containing gallic acid and methyl gallate may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage without exhibiting any pro-oxidant effect.

The objective of this study was to examine the effects of processing methods of corn grains on protein and starch degradability in the rumen by three ruminally cannulated dry Holstein cows. The corns for these experiments were untreated; whole corn L(density; 660 g/ N), whole corn H(density; 740 g/ N), and treated by four different types: Ground corn, 3.8 mm, 2.8 mm, and 1.5 mm flaked corn. The results obtained were summarized as follows : For 48 hrs, the protein degradabilities were high in order, ground corn, 1.5 mm, 2.8 mm, and 3.8 mm flaked corn(82.6, 76.5, 64.5, and 33.9%, respectively). Flaked corn grains were degraded lower than ground corn. However, as increasing the processing degree of flaking, the protein degradabilities, from 4 hrs to 48 hrs, were increased. The starch degradabilities on 48 hrs were higher in 1.5 and 2.8 mm flaked corns, ground corn, 3.8 mm flaked corn(99.1, 91.5, 89.5, and 68.9%, respectively) than whole corn L(32.0%) and whole corn H(20.5%)(P

GaN-based heterostructure devices are of interest for pressure and stress sensing applications due to their potential for use at high temperatures and in caustic environments. We have grown n-GaN/u-AlGaN/n-GaN heterostructure devices on sapphire substrates by organometallic vapor phase epitaxy (OMVPE) using the epitaxial layer overgrowth (ELO) method. The devices were fabricated with varying AlGaN layer thickness and composition. Current-voltage (I-V) characteristics were obtained to characterize the performance of these devices under hydrostatic pressures up to 500 MPa. For a fixed bias, the current was observed to decrease in magnitude with increasing hydrostatic pressure for all devices tested. The current modulation is attributed to piezoelectric effects. Specifically, the polarization charge densities at both GaN/AlGaN interfaces are sensitive to changes in the hydrostatic pressure, and these charges affect the shape of the potential barrier and the current. Changes in the AlGaN layer thickness and composition modify the interfacial polarization, with thicker AlGaN layers and higher Al content increasing the effect of pressure on the observed I-V characteristics. The decreases in current magnitude with increasing pressure are linear over the pressure range tested. In order to quantify the performance of these devices, we calculate a pressure gauge factor based on a normalized change in current divided by the change in pressure. Values obtained range from 0.1–1.0 GPa−1, consistent with our previously published results for a single device. In addition, the turn-on voltages under both forward and reverse bias conditions are observed to increase with increasing AlGaN layer thickness and composition, a result that agrees with our device model. These turn-on voltages are governed by different mechanisms in the forward and reverse bias directions. Under forward bias, the mechanism is a transition from a thermionic to a tunneling process. However, under reverse bias, the turn-on occurs when the total electric field changes sign in the AlGaN layer.

Anodized aluminum oxide (AAO) membranes consist of locally highly ordered nanopores. The pore diameter (20-200 nm) and pore-to-pore distance are controlled through the anodizing voltage and the choice of etching solution. High aspect ratio over 1,000 can easily be achieved which makes AAO membranes the ideal templates for making nanowires and nanotubes. In this work, the early stage of nanopore formation was studied in-situ with the use of small angle x-ray scattering (SAXS) and glazing incidence GISAXS techniques. The nanopores were found to grow as a function of the square root of growth time. The resulting short nanopores or nanowells with length below 200 nm were further characterized with use of SEM and AFM. These AAO nanowells showed interference color. Their reflectance UV-Vis spectra indicated strong angular dependence and can be understood with a simple single layer (nanoporous alumina over aluminum) model. These spectra are influenced by the nanowells thickness and diameter. Therefore, large array of interferometric AAO nanowells sensors are possible. When these nanowells are coated with Ag or Au thin films, in addition to enhanced interference color, highly sensitive surface enhanced Raman scattering (SERS) effect has been observed. These results will be presented.