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This paper employs the 0.2 μm ETRI GaN HEMT process on SiC to develop a Ku-band GaN low-noise amplifier monolithic microwave integrated circuit (MMIC) characterized by high-input power robustness for radar transceiver modules. A source degeneration inductor is employed to obtain the proposed amplifier’s stable operation and the compromised impedance trajectory of the maximum available gain and minimum noise figure. The analysis results show simultaneous gain and noise impedance matching, achieved using only a small number of passive elements. Furthermore, the proposed low-noise amplifier MMIC secures a linear gain of 21.3–22.6 dB, an input return loss of 19.6–21.4 dB, and a noise figure of 1.7–1.8 dB in the 15–16 GHz frequency range. It also exhibits an input 1 dB compression point of 0.4–1.5 dBm in the single-tone power test, and an input third-order intercept point of 5.8–10.1 dBm within the 15–16 GHz frequency range in the two-tone intermodulation distortion test.

Abstract Background In the process of finding the causative variant of rare diseases, accurate assessment and prioritization of genetic variants is essential. Previous variant prioritization tools mainly depend on the in-silico prediction of the pathogenicity of variants, which results in low sensitivity and difficulty in interpreting the prioritization result. In this study, we propose an explainable algorithm for variant prioritization, named 3ASC, with higher sensitivity and ability to annotate evidence used for prioritization. 3ASC annotates each variant with the 28 criteria defined by the ACMG/AMP genome interpretation guidelines and features related to the clinical interpretation of the variants. The system can explain the result based on annotated evidence and feature contributions. Results We trained various machine learning algorithms using in-house patient data. The performance of variant ranking was assessed using the recall rate of identifying causative variants in the top-ranked variants. The best practice model was a random forest classifier that showed top 1 recall of 85.6% and top 3 recall of 94.4%. The 3ASC annotates the ACMG/AMP criteria for each genetic variant of a patient so that clinical geneticists can interpret the result as in the CAGI6 SickKids challenge. In the challenge, 3ASC identified causal genes for 10 out of 14 patient cases, with evidence of decreased gene expression for 6 cases. Among them, two genes (HDAC8 and CASK) had decreased gene expression profiles confirmed by transcriptome data. Conclusions 3ASC can prioritize genetic variants with higher sensitivity compared to previous methods by integrating various features related to clinical interpretation, including features related to false positive risk such as quality control and disease inheritance pattern. The system allows interpretation of each variant based on the ACMG/AMP criteria and feature contribution assessed using explainable AI techniques.

Objective This experiment was conducted to investigate the effect of grain-based pecking blocks on productivity and welfare status at two commercial broiler welfare-certified farms. Methods Production and welfare indicators were assessed at two farms (designated Farm A and B). Both farms had two windowless houses with forced tunnel-type ventilation and housed broilers at stocking densities of approximately 16.7 birds/m2 (Farm A) and 16.8 birds/m2 (Farm B). Each house was divided into two or three equal sections and was provided with or without pecking blocks. Grain-based pecking blocks, measuring 25 × 25 × 25 cm, were given to broilers in both farms at 1 block per 1,000 birds. Various parameters including productivity (body weight and flock uniformity), corticosterone levels (in fecal droppings and feathers), footpad dermatitis, hock burn, feather dirtiness, gait score, litter quality, body surface temperature, and volatile fatty acids in fecal samples were assessed at 26 days of age, whereas litter quality was analyzed at 13 and 26 days of age. Results There were no significant effects of providing pecking blocks on productivity (body weight and uniformity), fecal and feather corticosterone, welfare indicators (i.e., footpad dermatitis, hock burn, feather cleanliness, and gait score), and litter quality (i.e., moisture, nitrogen, and pH). No differences in body surface temperature between the control and enrichment treatments were noted in Farm B, but body surface temperatures of the head (p = 0.029) and legs (p = 0.011) in the enrichment vs. control group were elevated in Farm A. Butyrate concentration in the enrichment vs control group was higher in Farm B (p = 0.023), but this effect was not detected in Farm A. Conclusion It is concluded that grain-based pecking blocks did not affect performance and welfare indicators. Further studies are warranted to elucidate the potential impact of grain-based pecking blocks on gut health indicators.

The Dark Web is an internet domain that ensures user anonymity and has increasingly become a focal point for illegal activities and a repository for information on cyberattacks owing to the challenges in tracking its users. This study examined the classification of the Dark Web in relation to these cyber threats. We processed Dark Web texts to extract vector types suitable for machine learning classification. Traditional methods utilizing the entirety of Dark Web texts to generate features result in vectors including all words found on the Dark Web. However, this approach incorporates extraneous information in the vectors, diminishing learning effectiveness and extending processing duration. The research aimed to optimize the classification process by selectively focusing on keywords within each class, thereby curtailing word vector dimensions. This optimization was facilitated by leveraging the anonymity characteristic of the Dark Web and employing topic-modeling-based weight generation. These methods enabled the creation of word vectors with a constrained feature set, enhancing the distinction of Dark Web classes. To further improve classification performance, we integrated TextCNN with topic modeling weights. For validation, we employed two datasets and compared the performance of the model with other text classification algorithms, where the proposed model demonstrated superior effectiveness in Dark Web classification.

Today’s cyber-attacks have become increasingly sophisticated and diverse, targeting systems that hold sensitive information, creating the need for continuous cyber exercise and skill development for cyber professionals. Because cyber exercises require training activities and environments that can support a variety of situations, significant technological efforts have been made to build training environments. In line with technological trends, current cyber exercise simulations are being studied to create various cyber scenarios that can help build an intelligent cyber battlefield using big data and artificial intelligence (AI). This requires a large amount and different types of data for learning, as well as a technical system that can manage and update them periodically. The objective of this study is to develop network topology generation and traffic prediction technologies based on intelligent network traffic analysis and AI models for cyber exercise technology systems. To automate training network scenarios, a path generation technology based on graph theory was developed, and the network environment was analyzed based on the amount of transmission by building a software-defined network capable of analyzing and predicting network traffic. A comparison of AI models such as long short-term memory (LSTM), bidirectional LSTM (BiLSTM), and gated recurrent units (GRU) to predict the amount of transmission showed good performance, with BiLSTM showing a better prediction error. The proposed methodology provides insights that can be used to adjust training scenarios during the network design and operation phases, which is expected to help manage the network, increase efficiency, and address security issues.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Early molecular response (EMR) at 3 months is predictive of improved overall survival (OS) and progression-free survival (PFS) in patients with chronic myeloid leukemia in the chronic phase (CML-CP). Although about one-third of patients treated with first-line imatinib do not achieve EMR, long-term OS and PFS are still observed in most patients. DASCERN (NCT01593254) is a prospective, phase IIb, randomized trial evaluating a switch to dasatinib in patients who have not achieved EMR after 3 months of treatment with first-line imatinib. Early analysis demonstrated an improved major molecular response (MMR) rate at 12 months with dasatinib versus imatinib (29% vs. 13%, P=0.005). Here, we report results from the final 5-year follow-up. In total, 174 patients were randomized to dasatinib and 86 to remain on imatinib. Forty-six (53%) patients who remained on imatinib but subsequently experienced failure were allowed to cross over to dasatinib per protocol. At a minimum follow-up of 60 months, the cumulative MMR rate was significantly higher in patients randomized to dasatinib versus imatinib (77% vs. 44%, P

Gochang-gun, situated in Korea, has achieved the distinction of being the second city in the country to have all three UNESCO-designated natural environmentrelated World Heritage Sites, following in the footsteps of Jeju Island. UNESCO has conferred upon Gochang-gun the prestigious designations of a biosphere reserve, World Natural Heritage (Gochang-Buan mudflat), and World Geopark (Jeonbuk West Coast Geopark). Notably, the entire administrative district has been designated as a UNESCO Biosphere Reserve, signifying its role as a meticulously preserved region of outstanding natural beauty and ecological significance. Within this UNESCO Biosphere Reserve, the core areas encompass remarkable features, including the Gochang-Buan Mudflat, Ungok Wetland, Dolmen World Cultural Heritage sites, Seonunsan Provincial Park, and Dongrim Reservoir. In pursuit of a comprehensive ecological map of Gochang-gun, the National Institute of Ecology (NIE) conducted an extensive two-year ecological survey and biotope survey from 2021 to 2022. Ecological spatial data was meticulously compiled based on the results of these surveys. The resulting Biotope map provides detailed information on various attributes, encompassing Biotope types, Biotope grades, land cover status, land use status, and topographic details. This dataset is formally registered and rigorously managed, employing the Digital Object Identifier (DOI) system. The primary aim of this paper is to provide a comprehensive introduction to each attribute of the Gochang-gun Biotope map, which represents a detailed collection of spatial ecology data for the region. The intent is to make this data readily accessible for future research and studies, thereby advancing our understanding of Gochang-gun’s distinctive ecological and cultural heritage.

Abstract Background Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. Methods We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. Results We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3− patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. Conclusion Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies. Graphical Abstract

The inclusion of exogenous phytase in P- and Ca-deficient diets of broilers to address the growing concern about excessive P excretion into the environment over the years has been remarkably documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with a meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to achieve the following: (1) quantitatively summarize the size of phytase effect on growth performance, bone strength and mineralization in broilers fed diets deficient in P and Ca and (2) estimate and explore the heterogeneity in the effect size of outcomes using subgroup and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration’s SYRCLE risk of bias checklists for animal studies. Applying the random effects models, Hedges’ g effect size of supplemented phytase was calculated using the R software (version 4.3.3, Angel Food Cake) to determine the standardized mean difference (SMD) at a 95% confidence interval. Subgroup analysis and meta-regression were used to further explore the effect size heterogeneity (PSMD ≤ 0.05, I2 > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and improves FCR at each time point of growth (p < 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (p < 0.0001) of broilers fed P- and Ca-deficient diets. The results of the subgroup and meta-regression analyses showed that the age and strain of broiler, dietary P source, and the duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary-available phosphorus and calcium and improve ADFI, BWG, and FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and the bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and the duration of phytase exposure rather than the dosage.

Abstract Background Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder, caused by a loss‐of‐function of either TSC1 or TSC2 gene. However, in 10%–15% TSC patients there is no pathogenic variant identified in either TSC1 or TSC2 genes based on standard clinical testing. Methods In this study, genome sequencing was performed for families with clinical diagnosis of TSC with negative results from TSC1 and TSC2 single‐gene tests. Results Herein, we report a family presenting a classical TSC phenotype with an unusual, complex structural variant involving the TSC1 gene: an intrachromosomal inverted insertion in the long arm of chromosome 9. We speculate that the inverted 9q33.3q34.13 region was inserted into the q31.2 region with the 3′‐end of the breakpoint of the inversion being located within the TSC1 gene, resulting in premature termination of TSC1. Conclusions In this study, we demonstrate the utility of genome sequencing for the identification of complex chromosomal rearrangement. Because the breakpoints are located within the deep intronic/intergenic region, this copy‐neutral variant was missed by the TSC1 and TSC2 single‐gene tests and contributed to an unknown etiology. Together, this finding suggests that complex structural variants may be underestimated causes for the etiology of TSC.

ABSTRACT: The present study was conducted to assess the animal welfare status of broiler chickens raised in conventional and welfare-certified farms. One conventional farm (30,000 birds/house, 1,488 m2/house, 2 houses) and one animal welfare-certified farm (32,000 birds/house, 1,920 m2/house, 2 houses) were selected to measure productivity, stress responses, and animal welfare indicators in 3 broiler flocks (2 farms/season, n = 6 flocks/farm type) during summer, autumn, and spring. Upon farm visits, body weight, uniformity, and animal welfare indicators (i.e., fecal and feather corticosterone, footpad dermatitis, hock burn, feather dirtiness, and gait score) were measured at 26 d posthatch. Also, moisture, nitrogen, and pH of litter, light intensity, ammonia concentration, and body surface temperature of head, chest, and legs were measured. There was no difference in body weight and uniformity between farm types. Fecal corticosterone concentrations were higher (P = 0.021) in welfare-certified vs. conventional farm, but no significant difference was found in feather corticosterone. Welfare-certified vs. conventional farm had lower percentages of hock burn (P = 0.018), feather dirtiness scores (P = 0.009), and gait score (P = 0.040), and there was no difference in footpad dermatitis. Nitrogen content in litter samples tended to be higher in conventional vs. welfare-certified farms (P = 0.094), and there was no difference in moisture and pH between farm types. Ammonia concentration within the broiler houses was not different between 2 farms. However, animal welfare farm was found to be brighter than conventional farm (P < 0.001). The body surface temperature of head, chest, and legs was not different between farm types. In conclusion, the welfare-certified farm had higher welfare measures, including lower hock burn, feather dirtiness, and gait score, confirming an overall improvement in welfare indicators. However, the observation on the elevated feather corticosterone noted in welfare vs. conventionally raised chickens warrants further studies.

Abstract Background Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model. Methods A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells. Results Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%. Conclusions Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R2 = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.

The maintenance of ion balance in closed hydroponic solutions is essential to improve the crop quality and recycling efficiency of nutrient solutions. However, the absence of robust ion sensors for key ions such as P and Mg and the coupling of ions in fertilizer salts render it difficult to effectively manage ion-specific nutrient solutions. Although ion-specific dosing algorithms have been established, their effectiveness has been inadequately explored. In this study, a decision-tree-based dosing algorithm was developed to calculate the optimal volumes of individual nutrient stock solutions to be supplied for five major nutrient ions, i.e., NO3, K, Ca, P, and Mg, based on the concentrations of NO3, K, and Ca and remaining volume of the recycled nutrient solution. In the performance assessment based on five nutrient solution samples encompassing the typical concentration ranges for leafy vegetable cultivation, the ion-selective electrode array demonstrated feasible accuracies, with root mean square errors of 29.5, 10.1, and 6.1 mg·L-1 for NO3, K, and Ca, respectively. In a five-step replenishment test involving varying target concentrations and nutrient solution volumes, the system formulated nutrient solutions according to the specified targets, exhibiting average relative errors of 10.6 ± 8.0%, 7.9 ± 2.1%, 8.0 ± 11.0%, and 4.2 ± 3.7% for the Ca, K, and NO3 concentrations and volume of the nutrient solution, respectively. Furthermore, the decision tree method helped reduce the total fertilizer injections and carbon emissions by 12.8% and 20.6% in the stepwise test, respectively. The findings demonstrate that the decision-tree-based dosing algorithm not only enables more efficient reuse of nutrient solution compared to the existing simplex method but also confirms the potential for reducing carbon emissions, indicating the possibility of sustainable agricultural development.

Abstract Global climate change has compelled many to rely on photovoltaic (PV) technology to meet the highly demanding energy needs of urban areas. In particular, transparent photovoltaic (TPV) devices can be utilized for building windows, not only supplying electric energy but also improving the overall thermal efficiency of a building. In this work, NiO/ZnO wide‐bandgap oxide TPV heterojunctions are fabricated with Ag nanowire (NW) top electrodes and their PV characteristics are investigated. Special attention is paid to the contributions of surface plasmon (SP) excitation in AgNWs to the PV performance of the TPV device. Light polarized perpendicular to the AgNW axis induces a localized SP resonance in AgNWs at a wavelength of 400 nm, as shown by optical measurements and calculations. The investigation on how the plasmonic AgNWs affect real‐space electric potential distributions and local current‐voltage characteristics of the TPV devices uses Kelvin probe force microscopy and current‐sensing atomic force microscopy, respectively. The spatial redistribution and transport of photogenerated charge carriers strongly depend on the polarization as well as the wavelength of incident light. The results demonstrate that the AgNW‐based top electrodes boost the wavelength‐selective absorption and the effective collection of photocarriers in TPV devices.

With the proliferation of network systems, the boundaries between cyber and physical environments are blurring, leading to an increased risk of sophisticated cyber-attacks equipped with advanced technologies. In particular, as advancements in artificial intelligence through learning models have led to automated attacks and attack scenarios, countries are implementing cyber training and constructing training systems to respond to cyber security threats. This cyber training is based on existing cyber-attacks and conducted in virtual spaces similar to reality, generating network traffic through simulators and focusing on training for attack response and cyber resilience. However, the exponential increase in the number of network-based devices and the amount of network traffic they generate is leading to a gradual increase in threats to cyber security. In this study, first investigated the existing port number-based network traffic classification technologies and payload-based network traffic classification technologies to identify their shortcomings in the current network environment. We then categorized existing studies into supervised, unsupervised, and reinforcement learning to analyze the technology of classifying network traffic based on learning models as well as classification methods, procedures, performance standards, evaluation methods, quality of service/quality of experience, etc. Based on the analysis, presented limitations for application to training networks according to the learning method and suggested recommendations for establishing future research directions. Therefore, refining learning model-based network traffic classification technology will contribute to the construction of automated cyber training grounds such as cyber-attack–defense scenarios, network traffic anomaly detection, and maximizing cumulative rewards.

The continuous advancement of information technology has improved user convenience but has also made it more vulnerable to cyber attacks. In particular, attackers use advanced techniques to perform new attacks. In cyber security, such attacks are defined as unknown attacks and target previously undetected vulnerabilities or excavate gaps in the system. Because these attacks are unidentified or unanalyzed, they are difficult to identify in signature-based misuse detection that learns rules or patterns. Furthermore, anomaly-based detection that learns from normal data to detect outliers cannot detect unknown attacks accurately, because it does not distinguish between known and unknown attacks. To overcome these problems, this study applied open-set recognition with dissimilarity weight (OSRDW). An OSRDW method was used to effectively train the extreme value distribution, which was calculated by applying the dissimilarity weight, through which the weights of the unknown attack were calculated and classified as unknown attacks. Through research analysis, unknown attacks could be categorized into two types, and three datasets (NSL-KDD, UNSW-NB15, CICIDS-2017) with 140,000–2,500,000 rows were used in the experiment. For the first type of unknown attack, the unknown attack detection rate of the proposed method was approximately 10%–20% better than that of the conventional method. For the second type of unknown attack, the accuracy and unknown attack detection rate were higher for the proposed method. The experimental results confirmed that the proposed method had better performance in detecting unknown attacks and could detect various attacks in the three datasets.

South Korea has a temperate climate with four distinct seasons. However, summers are extremely hot and humid, which negatively affects industrial animal production. Hanwoo are native cattle that have traditionally been raised in the natural environment of Korea. The present study investigated the effects of birth and lactation season on the birth and weaning weights of Hanwoo calves. Data were collected from 100 local breeding farms between 2016 and 2021. A total of 56,970 (males, 29,530; females, 27,440) Hanwoo calves were classified according to sex or birth and weaning season (March–May, spring; June–August, summer; September–November, fall; and December–February, winter). The birth weight of Hanwoo calves differed according to the birth season. As such, birth weight of the summer-born calves was the lowest. Additionally, the 90-day weaning weight was positively correlated with birth weight. Interestingly, however, the 90-day weaning weight was not related to the birth season but was related to the 2-month seasonal effect during the lactation period. Furthermore, the 90-day weaning weight was the lowest during the summer lactation period. In the beef cattle industry, daily weight gain is an important economic characteristic related to feed efficiency and growth. Our findings will contribute the management of Hanwoo cattle and analysis of changes in economic characteristics due to high temperatures.

Abstract CRISPR/Cas9 and Cas12a belonging to the Class II CRISPR system are characterized by a single-component effector protein. Despite unique features of Cas12a like DNA cleavage with 5′ staggered ends and a single crRNA, Cas12a has not been adopted in biotechnological applications to the similar extent as Cas9. To better understand the CRISPR/Cas12 systems, we selected two candidates, designated mgCas12a-1 and mgCas12a-2, from an analysis of the human microbiome metagenome (mg) and provided biochemical characterization. These new Cas12a proteins shared about 37% identity in amino acid sequences and shared the same direct repeat sequences in the crRNA with FnCas12a from Francisella novicida. The purification yield of the recombinant proteins was up to 3.6-fold greater than that of FnCas12a. In cell-free DNA cleavage assays, both mgCas12a proteins showed the higher cleavage efficiencies when Mn2+ was provided with KCl (

Pirfenidone (PRF) is the first FDA-approved API in the treatment of idiopathic pulmonary fibrosis (IPF). However, PRF induces serious side effects, such as photophobia and gastrointestinal disorder. PRF inhalation can be expected with a lower effective dose and reduced side effects. In this study, PRF was prepared as inhalable co-spray-dried particles for dry powder inhalation. Mannitol, L-leucine (Leu), and NaCl were used as a stabilizer. The kinds and ratios of stabilizers affecting the physicochemical properties of particles were analyzed, including particle size and surface composition, because of the surface enrichment properties of Leu, the most effective stabilizer. The co-spray-dried PRF and Leu microparticle (SD-PL1:1) have the smallest size and highest aerosol performance. The bioavailability was confirmed by in vivo pharmacokinetics (PK) studies. In addition, in vivo pharmacodynamics (PD) experiments were conducted using a bleomycin-induced IPF rat model. In vivo PK experiments demonstrated that pulmonary administration of SD-PL1:1 was 4 times more effective than the oral route. Similar to the PK results, the therapeutic effect was improved when SD-PL1:1 was administered via the pulmonary route compared to the oral route.

In this paper, using the 0.2 μm ETRI GaN HEMT process, we developed a C-band GaN dual-feedback low-noise amplifier MMIC for an RF receiver module that requires high-input power robustness. By applying a feedback microstrip line at the source of the transistor and series resistor-capacitor (RC) feedback between the gate and the drain of the transistor, we obtained stable amplifier operation and a compromised impedance trace for both input impedance matching and noise matching while suppressing performance degradation of the maximum available gain and minimum noise figure. The developed low-noise amplifier MMIC, which implements simple matching circuits by using biasing elements as matching elements, had a linear gain of more than 21.4 dB and a noise figure of less than 1.91 dB in the wide bandwidth of 4.3–7.4 GHz. Under the single-tone power test, the low-noise amplifier MMIC had an output P1dB of 14.3–20.1 dBm, and the two-tone intermodulation distortion measurement exhibited an input third-order intercept point (IIP3) of 2.2–5.6 dBm in the same frequency range as the above.

Abstract Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). PACSIN2, a novel Cobll1 binding protein, activates TKI‐induced apoptosis in K562 cells, and this activation is suppressed by Cobll1 through the interaction between PACSIN2 and Cobll1. PACSIN2 also binds and inhibits SH3BP1 which activates the downstream Rac1 pathway and induces TKI resistance. PACSIN2 competitively interacts with Cobll1 or SH3BP1 with a higher affinity for Cobll1. Cobll1 preferentially binds to PACSIN2, releasing SH3BP1 to promote the SH3BP1/Rac1 pathway and suppress TKI‐mediated apoptosis and eventually leading to TKI resistance. Similar interactions among Cobll1, PACSIN2, and SH3BP1 control hematopoiesis during vertebrate embryogenesis. Clinical analysis showed that most patients with CML have Cobll1 and SH3BP1 expression at the BC phase and BC patients with Cobll1 and SH3BP1 expression showed severe progression with a higher blast percentage than those without any Cobll1, PACSIN2, or SH3BP1 expression. Our study details the molecular mechanism of the Cobll1/PACSIN2/SH3BP1 pathway in regulating drug resistance and BC progression in CML.

Abstract Due to their extraordinarily large optical absorption coefficients, transition metal dichalcogenides (TMDs) are gaining more and more attention for photovoltaic applications. Improving the device performance of a TMD solar cell requires an optimal device architecture and reliable fabrication processes. Metal/WS2‐multilayer/metal heterojunctions are fabricated using lithography‐free processes. 20 nm thick WS2 flakes are exfoliated on template‐stripped Ag bottom electrodes, and then 10 nm thick Au top electrodes with a diameter of 2 µm are evaporated on the WS2 surface using holey carbon films as shadow masks. Current‐sensing atomic force microscope measurements reveal that the Au/WS2/Ag devices exhibit prominent rectifying characteristics, indicating the formation of Schottky diodes. The power conversion efficiency of the Schottky junction is as high as 5.0%, when illuminated by a light‐emitting diode with a peak wavelength of 625 nm and a power density of 2.5 mW cm−2. These devices also possess broadband and incident‐angle‐insensitive absorption capability due to the very large refractive indices and extremely small thickness of the WS2 flakes. The simple fabrication procedures proposed in this work demonstrate high‐performance and high‐yield TMD photovoltaic devices.

Corrugated surface microparticles comprising levofloxacin (LEV), chitosan and organic acid were prepared using the 3-combo spray drying method. The amount and the boiling point of the organic acid affected the degree of roughness. In this study, we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler. HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution. The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles. The FPF value of HMP175 L20 was 41.3% ± 3.9% compared with 25.6% ± 7.7% of HMF175 L20. Corrugated microparticles also showed better aerosolization, decreased x-axial velocity, and variable angle. Rapid dissolution of drug formulations was observed in vivo. Low doses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally. Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.

Abstract Advanced resistive random‐access memory (ReRAM) devices based on resistive switching (RS) have been intensely studied for future high‐density nonvolatile memory devices owing to their high scalability, simplified integration, fast operation, and ultralow power consumption. Among the recently considered active media, diverse carbon‐based media have emerged because of numerous benefits of simple chemical composition, desirable speed, and cost‐effective scalability. However, these media are still susceptible to undesirable reliability issues, including poor endurance and retention and uncontrollable operation voltage distribution. In this study, an oxynitride amorphous carbon active medium governed by appropriate nitrogen content during growth is introduced to facilitate high electrical stability, such as a distinct pulse endurance of more than 107 cycles, a high retention time of 105 s at 85 °C, and increased uniformity in the SET/RESET distribution with thermally robust RS stability even at a high annealing temperature of 400 °C. The findings are possibly the result of adapting an sp2–sp3 conversion nature assisted by the presence of pyridinic N or pyrrolic N as a substitution reaction.

Background/objective: Laparoscopic totally extraperitoneal (TEP) herniorrhaphy is among the current leading inguinal hernia repair methods. This study aimed to investigate the safety and feasibility of a junior surgeon's first experience with laparoscopic TEP herniorrhaphy. Methods: A retrospective review was performed between January 2017 and December 2019 to analyze the medical records of patients with inguinal hernia who underwent laparoscopic TEP herniorrhaphy. The operative outcomes and complications of patients undergoing surgery by an experienced surgeon (group A, n = 100) were compared with those undergoing surgery by a junior surgeon (group B, n = 100). Results: The mean operative time for group B was significantly longer than that for group A (52.0 ± 15.1 min vs 60.1 ± 17.4 min; P = 0.03). A statistical difference was also found in the mean postoperative stay (1.1 ± 0.3 d vs 1.4 ± 0.7 d; P = 0.02) between the two groups. There were 2 and 3 cases of recurrence in these two groups respectively (P = 0.72). Considering the operating time as a variable of learning curve, significant stabilization can be achieved after 30 cases (67.3 ± 17.8 min vs 53.1 ± 11.1 min; P = 0.02). Conclusions: The surgical outcomes of laparoscopic TEP herniorrhaphy performed by a well-trained junior surgeon were similar to the outcomes of an experience surgeon.

Background Postoperative pain occurring after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is difficult to control because of extensive surgical injuries and long incisions. We assessed whether the addition of a four-quadrant transabdominal plane (4Q-TAP) block could help in analgesic control. Methods Seventy-two patients scheduled to undergo elective CRS with HIPEC and intravenous patient-controlled analgesia (IV PCA) were enrolled. The patients received 4Q-TAP blocks in a 10 ml mixture of 2% lidocaine and 0.75% ropivacaine per site (4Q-TAP group, n = 36) or normal saline (control group, n = 33). Oxycodone in the post-anesthesia care unit (PACU) and pethidine or tramadol in the ward were used as rescue analgesics. The primary outcome was less than 3 times of rescue analgesic administration (%) in the ward for 5 postoperative days. Secondary endpoints included oxycodone requirement in PACU, fentanyl doses of IV PCA, morphine milligram equivalent (MME) of total opioid use, hospital stay, and postoperative complications. Results During 5 postoperative days, there was no difference in pain scores and total rescue analgesic administration between two groups. However, the use of oxycodone in PACU (P = 0.011), fentanyl requirement in IV PCA (P = 0.029), and MME/kg of total opioid use (median, 2.35 vs. 3.21 mg/kg, P = 0.009) were significantly smaller in the 4Q-TAP group. Hospital stay and incidence of postoperative morbidity were similar in both groups. Conclusions The 4Q-TAP block enhanced multimodal analgesia and decreased opioid requirements in patients with CRS with HIPEC, but did not change postoperative recovery outcomes.

Researchers have continuously sought effective ways to detect unknown (zero-day) cyberattacks in real time. Most current methods rely on pattern-recognition to identify known threats when they appear. Recently, machine learning anomaly detection tools that train a model on normal network data have been used to identify outliers representing unknown attacks. However, detecting unknown attacks is difficult because of a lack of information on unknown attacks, class imbalance in the data, or failure to accurately detect attacks with normal patterns. To overcome these problems, this study applied data discretization and decision-boundary data point analyses to scrutinize patterns near the thresholds of uncertainty. A novel discretization method was used to effectively train a model for the fuzzy c-means feature analysis of data points at the decision boundary, through which adversarial features were detected and classified based on their entropy. Consequently, it was possible to identify incorrectly detected attack data distributed near the model’s decision boundary. The NSL-KDD dataset, which is commonly used to evaluate ML intrusion detection systems, was used to evaluate the proposed method. The results showed that our model successfully identified attacks at the decision boundary and that its performance can be improved through classification. In addition, after classification, it was confirmed that the accuracy of detecting DoS attacks improved by 5 to 7%, Probe by 7 to 10%, R2L by 4 to 7%, and U2R by 1 to 9%, compared with that of existing models.

Abstract Background The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. Methods To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. Results A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. Conclusions This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 ( https://clinicaltrials.gov/ct2/show/NCT01207440 ).

This study investigated the effects of heat stress on milk production in Korean Holstein cows using large-scale data. Heat stress was assessed using the temperature-humidity index (THI). Weather records (2016 to 2020) were collected from 70 regional weather stations using an installed automated surface observing system (ASOS). A dataset of 2,094,436 milk production records from 215,276 Holstein cows obtained from the Dairy Cattle Genetic Improvement Center was analyzed. Stepwise selection was used to select the input variables, including the daily maximum THI (THI_max). Least-squares means were calculated for milk yield, fat and protein corrected milk (FPCM), fat and protein yield, fat-to-protein ratio, solids not fat, and lactation persistency. Segmented linear regression analysis determined the break points (BPs) of the THI_max. Over the five years, heat stress exposure increased, particularly from May to September. This study identified BPs around THI_max of 80–82 for milk yield and FPCM. Similar patterns for other milk traits were observed, which significantly decreased beyond their respective BPs. These findings indicate that THI variations adversely affect milk yield and composition in dairy cows, highlighting the importance of appropriate feeding management strategies to ensure the optimal productivity of Holstein cows under varying climatic conditions.

Abstract Parkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

In chronic myelogenous leukemia (CML), treatment-free remission (TFR) is defined as maintaining a major molecular response (MMR) without a tyrosine kinase inhibitor (TKI), such as imatinib (IM). Several studies have investigated the safety of the first TFR (TFR1) attempt and suggested recommendation guidelines for such an attempt. However, the plausibility and predictive factors for a second TFR (TFR2) have yet to be reported.The present study included 21 patients in chronic myeloid leukemia who participated in twice repeated treatment stop attempts. We develop a mathematical model to analyze and explain the outcomes of TFR2. Our mathematical model framework can explain patient-specific molecular response dynamics. Fitting the model to longitudinal BCR-ABL1 transcripts from the patients generated patient-specific parameters. Binary tree decision analyses of the model parameters suggested a model based predictive binary classification factor that separated patients into low- and high-risk groups of TFR2 attempts with an overall accuracy of 76.2% (sensitivity of 81.1% and specificity of 69.9%). The low-risk group maintained a median TFR2 of 28.2 months, while the high-risk group relapsed at a median time of 3.25 months. Further, our model predicted a patient-specific optimal IM treatment duration before the second IM stop that could achieve the desired TFR2 (e.g., 5 years).

Background We hypothesized in this study that the characteristics of retear cases vary according to surgeon volume and that surgical outcomes differ between primary and revision arthroscopic rotator cuff repair (revisional ARCR). Methods Surgeons performing more than 12 rotator cuff repairs (RCRs) per year were defined as high-volume surgeons, and those performing fewer than 12 RCRs were considered low-volume surgeons. Of the 47 patients who underwent revisional ARCR at our clinic enrolled in this study, 21 cases were treated by high-volume surgeons and 26 cases by low-volume surgeons. In all cases, the interval between primary surgery and revisional ARCR, degree of “acromial scuffing,” number of anchors, RCR technique, retear pattern, fatty infiltration, retear size, operating time, and clinical outcome were recorded. Results During primary surgery, significantly more lateral anchors (p=0.004) were used, and the rate of use of the double-row repair technique was significantly higher (p

Abstract Understanding the excitonic processes at the interfaces of fluorescent π-conjugated molecules and metal electrodes is important for both fundamental studies and emerging applications. Adsorption configurations of molecules on metal surfaces significantly affect the physical characteristics of junctions as well as molecules. Here, the electronic structures and optical properties of molecular assemblies/Au interfaces were investigated using scanning probe and photoluminescence microscopy techniques. Scanning tunneling microscopy images and tunneling conductance spectra suggested that the self-assembled molecules were physisorbed on the Au surface. Visible-range photoluminescence studies showed that Au thin films modified the emission spectra and reduced the lifetime of excitons. Surface potential maps, obtained by Kelvin probe force microscopy, could visualize electron transfer from the molecules to Au under illumination, which could explain the decreased lifetime of excitons at the molecule/Au interface.

Recently, summer temperatures have frequently been abnormal in Korea owing to global warming. In summer, a decrease in feed intake rate and biological activity were observed in Hanwoo (Korean Native Cattle), leading to lower production rates in the industry. However, the precise scale of damage was not reported as with other animals of economic value. This study was conducted to investigate the effects of birth season on birth weight in Hanwoo. Data were collected from 100 local breeding farms from 2016 to 2019. A total of 41,081 Hanwoo calves were classified and analyzed by sex, year, month, and season (March–May, spring; June–August, summer; September–November, fall; and December–February, winter) of birth. The birth weight of Hanwoo calves differed according to birth month. The average birth weight of male calves was 30.47 kg and that of female calves was 28.16 kg. Hanwoo birth weight was the highest in March-born calves and the lowest in July-born calves. The birth weights of calves born in February, March, April, November, and December were significantly larger than those of calves born in July. In addition, the birth weight of Hanwoo calves from the summer was significantly lower than that of calves born in other seasons. Furthermore, Hanwoo steer slaughter age showed a negative correlation, whereas carcass weight had a positive correlation with birth weight. In the beef cattle industry, birth weight is a very important economic characteristic that is related to growth rate. These data will contribute toward planning the reproduction of Hanwoo and analysis of changes in characteristics of economic value owing to high temperatures.

Abstract Successful cell therapy for Parkinson’s disease (PD) requires large numbers of homogeneous ventral mesencephalic dopaminergic (vmDA) precursors. Enrichment of vmDA precursors via cell sorting is required to ensure high safety and efficacy of the cell therapy. Here, using LMX1A-eGFP knock-in reporter human embryonic stem cells, we discovered a novel surface antigen, trophoblast glycoprotein (TPBG), which was preferentially expressed in vmDA precursors. TPBG-targeted cell sorting enriched FOXA2+LMX1A+ vmDA precursors and helped attain efficient behavioral recovery of rodent PD models with increased numbers of TH+, NURR1+, and PITX3+ vmDA neurons in the grafts. Additionally, fewer proliferating cells were detected in TPBG+ cell-derived grafts than in TPBG− cell-derived grafts. Our approach is an efficient way to obtain enriched bona fide vmDA precursors, which could open a new avenue for effective PD treatment.

Abstract Integration of distinct materials to form heterostructures enables the proposal of new functional devices based on emergent physical phenomena beyond the properties of the constituent materials. The optical responses and electrical transport characteristics of heterostructures depend on the charge and exciton transfer (CT and ET) at the interfaces, determined by the interfacial energy level alignment. In this work, heterostructures consisting of aggregates of fluorescent molecules (DY1) and 2D semiconductor MoS2 monolayers are fabricated. Photoluminescence spectra of DY1/MoS2 show quenching of the DY1 emission and enhancement of the MoS2 emission, indicating a strong electronic interaction between these two materials. Nanoscopic mappings of the light‐induced contact potential difference changes rule out the CT process at the interface. Using femtosecond transient absorption spectroscopy, the rapid interfacial ET process from DY1 aggregates to MoS2 and a fourfold extension of the exciton lifetime in MoS2 are elucidated. These results suggest that the integration of 2D inorganic semiconductors with fluorescent molecules can provide versatile approaches to engineer the physical characteristics of materials for both fundamental studies and novel optoelectronic device applications.

The conventional dosage form of Ethyol® (amifostine), a sterile lyophilized powder, involves reconstituting it with 9.7 mL of sterile 0.9% sodium chloride in accordance with the United States Pharmacopeia specifications for intravenous infusion. The purpose of this study was to develop inhalable microparticles of amifostine (AMF) and compare the physicochemical properties and inhalation efficiency of AMF microparticles prepared by different methods (jet milling and wet ball milling) and different solvents (methanol, ethanol, chloroform, and toluene). Inhalable microparticles of AMF dry powder were prepared using a wet ball-milling process with polar and non-polar solvents to improve their efficacy when delivered through the pulmonary route. The wet ball-milling process was performed as follows: AMF (10 g), zirconia balls (50 g), and solvent (20 mL) were mixed and placed in a cylindrical stainless-steel jar. Wet ball milling was performed at 400 rpm for 15 min. The physicochemical properties and aerodynamic characteristics of the prepared samples were evaluated. The physicochemical properties of wet-ball-milled microparticles (WBM-M and WBM-E) using polar solvents were confirmed. Aerodynamic characterization was not used to measure the % fine particle fraction (% FPF) value in the raw AMF. The % FPF value of JM was 26.9 ± 5.8%. The % FPF values of the wet-ball-milled microparticles WBM-M and WBM-E prepared using polar solvents were 34.5 ± 0.2% and 27.9 ± 0.7%, respectively; while the % FPF values of the wet-ball-milled microparticles WBM-C and WBM-T prepared using non-polar solvents were 45.5 ± 0.6% and 44.7 ± 0.3%, respectively. Using a non-polar solvent in the wet ball-milling process resulted in a more homogeneous and stable crystal form of the fine AMF powder than using a polar solvent.

The investigation of quantitative phenotypic traits resulting from the interaction between targeted genotypic traits and environmental factors is essential for breeding selection. Therefore, plot-wise controlled environmental factors must be invariable for accurate identification of phenotypes. However, the assumption of homogeneous variables within the open-field is not always accepted, and requires a spatial dependence analysis to determine whether site-specific environmental factors exist. In this study, spatial dependence within the kenaf breeding field was assessed in a geo-tagged height map derived from an unmanned aerial vehicle (UAV). Local indicators of spatial autocorrelation (LISA) were applied to the height map using Geoda software, and the LISA map was generated in order to recognize the existence of kenaf height status clusters. The spatial dependence of the breeding field used in this study appeared in a specific region. The cluster pattern was similar to the terrain elevation pattern of this field and highly correlated with drainage capacity. The cluster pattern could be utilized to design random blocks based on regions that have similar spatial dependence. We confirmed the potential of spatial dependence analysis on a crop growth status map, derived by UAV, for breeding strategy design with a tight budget.

The genus Hapalochlaena, including the blue-lined octopus Hapalochlaena fasciata (H. fasciata), is highly toxic. Venomous, blue-lined octopuses were recently found in Korea, but their toxicity, toxin composition, and distribution remain largely unknown. Here we estimated the geographic distribution of the organisms along the Korean coast and clarified their toxicity. Tetrodotoxin (TTX) was present in all three specimens of H. fasciata examined, although the toxicity varied largely between individuals. The mean TTX concentration in the whole body of the three specimens was 6.5 ± 2.2 μg/g (range 3.3–8.5 μg/g). Among the body parts examined, the salivary glands exhibited the highest concentration (22.4 ± 9.7 μg/g). From 2012 to 2021, 26 individuals were obtained nearly every month from different regions of the Korean coast. A non-fatal case of a blue-lined octopus bite was reported along the Korean coast in June 2015. This is the first report on the widespread distribution of blue-lined octopuses on the Korean coast and TTX detection. The widespread distribution of the TTX-bearing H. fasciata along the Korean coast within the temperate zone indicates that the species may soon become a serious health issue in Korea. The toxicity of this species is also a potentially significant human health risk.

Background/Aims Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. Methods In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.

Abstract Background We investigated the feasibility of the clinical application of non‐invasive transthoracic echocardiography for diagnosis of pulmonary arterial hypertension induced by dasatinib (D‐PAH) in chronic myeloid leukemia (CML). Methods A total of 451 CML patients who were examined by 2D‐echocardiography at least once at baseline and/or during dasatinib therapy as frontline (n = 196) and subsequent line (n = 255) therapies were included in this study. D‐PAH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg with relevant symptoms and the absence of other specific etiologies. Results A total of 847 echocardiographies were performed including at baseline (n = 255) and during dasatinib treatment (n = 592). During the median of 36.2 (0.1–181.8) months of dasatinib therapy, the level of RVSP gradually increased (Spearman's r = 0.2819, p 40 mm Hg without (asymptomatic, n = 27, 48.2%) or with symptoms (D‐PAH, n = 29, 51.8%). All asymptomatic patients maintained dasatinib therapy without further symptoms and the D‐PAH patients ultimately switched to other tyrosine kinase inhibitors. After dasatinib discontinuation, 13 (45%) and 15 (52%) patients showed RVSP normalization and gradual decrease, respectively. Conclusions Our large cohort study demonstrated that the gradual increment of RVSP might be induced by dasatinib and non‐invasive echocardiography can be fast way for early diagnosis as well as for monitoring of D‐PAH.

Abstract Leukapheresis is used for the mechanical removal of leukaemic cells in hyperleukocytosis. However, the effectiveness of leukapheresis remains unclear due to selection and confounding factors in the cohorts. We compared the effectiveness of leukapheresis among the subgroups according to either the 2016 World Health Organization classification or the number of cytogenetic abnormalities with a retrospective, single-centre study from January 2009 to December 2018. Acute myeloid leukaemia (AML, n = 212) and acute lymphoblastic leukaemia (ALL, n = 97) were included. The 30-day survival rates (95% confidence interval, 95% CI) for AML and ALL were 86.3% (81.6–90.9%) and 94.8% (90.3–99.2%), respectively. For AML, ‘primary AML with myelodysplasia-related changes’ and ‘AML with biallelic mutation of CEBPA’ showed better 30-day survival outcomes (P = 0.026) than the other subgroups. A higher platelet count after leukapheresis was associated with better 30-day survival in AML patients (P = 0.029). A decrease in blast percentage count after leukapheresis was associated with better 30-day survival in ALL patients (P = 0.034). Our study suggested that prophylactic platelet transfusion to raise the platelet count to 50 × 109/L or greater might improve clinical outcome in AML patients undergoing leukapheresis.

High levels for noise and a loss of true signal make the quantitative interpretation of nuclear medicine (NM) images difficult. An application of profile optimization using a sigmoidal function in this study was used to acquire the NM images with high quality. And the images were acquired by using three kinds of reconstruction method using each same sinogram: a standard filtered back-projection (FBP), an iterative reconstruction (IR) technique, and the sigmoidal function profile optimization (SFPO). Comparison of image according to reconstruction method was performed to show a superiority of the SFPO for imaging. The images reconstructed by using the SFPO showed an average of 1.49 times and of 1.17 times better in contrast than the results obtained using the standard FBP and the IR technique, respectively. Higher signal to noise ratios were obtained as an average of 12.30 times and of 3.77 times than results obtained using the standard FBP and the IR technique, respectively. This study confirms that reconstruction with SFPO (vs FBP and vs IR) can lead to better lesion detectability and characterization with noise reduction. It can be developed for future reconstruction technique for the NM imaging.

Ever since research attention was first paid to phenomics, it has mainly focused on the use of high throughput phenotyping for characterizing traits in an accurate and fast manner. It was recently realized that its use has huge potential in precision agriculture. However, the focus so far has mainly been on ”obtain large data set”, not on “how to analyze them”. Here, the expanded application of high throughput phenotyping combined with special dependence analysis is demonstrated to reveal the hidden field heterogeneity, using a kenaf field. Based on the method used in the study, the results showed that the growth of kenaf in the field was grouped into two, which led to a large variation of sources among replications. This method has potential to be applied to detect hidden heterogeneity, to be utilized and applied in plant breeding not only for better analysis, but also for better management of fields in precision agriculture.