Search

Abstract This study evaluates the diagnostic efficacy of automated machine learning (AutoGluon) with automated feature engineering and selection (autofeat), focusing on clinical manifestations, and a model integrating both clinical manifestations and CT findings in adult patients with ambiguous computed tomography (CT) results for acute appendicitis (AA). This evaluation was compared with conventional single machine learning models such as logistic regression(LR) and established scoring systems such as the Adult Appendicitis Score(AAS) to address the gap in diagnostic approaches for uncertain AA cases. In this retrospective analysis of 303 adult patients with indeterminate CT findings, the cohort was divided into appendicitis (n = 115) and non-appendicitis (n = 188) groups. AutoGluon and autofeat were used for AA prediction. The AutoGluon-clinical model relied solely on clinical data, whereas the AutoGluon-clinical-CT model included both clinical and CT data. The area under the receiver operating characteristic curve (AUROC) and other metrics for the test dataset, namely accuracy, sensitivity, specificity, PPV, NPV, and F1 score, were used to compare AutoGluon models with single machine learning models and the AAS. The single ML models in this study were LR, LASSO regression, ridge regression, support vector machine, decision tree, random forest, and extreme gradient boosting. Feature importance values were extracted using the “feature_importance” attribute from AutoGluon. The AutoGluon-clinical model demonstrated an AUROC of 0.785 (95% CI 0.691–0.890), and the ridge regression model with only clinical data revealed an AUROC of 0.755 (95% CI 0.649–0.861). The AutoGluon-clinical-CT model (AUROC 0.886 with 95% CI 0.820–0.951) performed better than the ridge model using clinical and CT data (AUROC 0.852 with 95% CI 0.774–0.930, p = 0.029). A new feature, exp(-(duration from pain to CT)3 + rebound tenderness), was identified (importance = 0.049, p = 0.001). AutoML (AutoGluon) and autoFE (autofeat) enhanced the diagnosis of uncertain AA cases, particularly when combining CT and clinical findings. This study suggests the potential of integrating AutoML and autoFE in clinical settings to improve diagnostic strategies and patient outcomes and make more efficient use of healthcare resources. Moreover, this research supports further exploration of machine learning in diagnostic processes.

Abstract Background High blood pressure variability (BPV) increases the risk of cardiovascular disease and may be better prognostic factor than blood pressure. Depressive mood is a common symptom among patients visiting primary care. This study aimed to investigate the association between depressive mood and high BPV among Korean primary care patients. Methods The Family Cohort Study in Primary Care (FACTS), conducted from April 2009 to November 2017, utilized a prospective cohort of Korean primary care patients, with a median follow-up period of 7.25 years. Depressive mood was assessed as a score of 21 points or more on the Korean-type Center for Epidemiologic Studies Depression scale. BP was measured at the initial visit and first and second follow-up visit. Visit-to visit SBP variability was analyzed using four metrics: intra-individual standard deviation, coefficient of variation, variation independent of mean, and average real variability. Logistic regression analysis was used to estimate the association of high BPV with depressive mood and other variables. Results Among 371 participants, 43 (11.6%) had depressive mood based on depression scores. Older age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.01–1.07) were associated with high SBP variability regardless of taking antihypertensive medication. Among participants taking antihypertensive medication, those with depressive mood had twice the risk of high SBP variability compared with those who did not (OR: 2.95, 95% CI: 1.06–8.20). Conclusions Depressive mood was associated with high visit-to-visit SBP variability in primary care patients taking antihypertensive medication, potentially indicating increased cardiovascular risk. Primary care physicians should therefore closely monitor BPV in patients with depressive symptoms and provide appropriate interventions.

In this paper, we propose a method for applying the p-ary m-sequence as a channel-searching pattern for rendezvous in the asymmetric channel model of cognitive radio. We mathematically analyzed and calculated the ETTR when the m-sequence is applied to the conventional scheme, and our simulation results demonstrated that the ETTR performance is significantly better than that of the JS algorithm. Furthermore, we introduced a new channel-searching scheme that maximizes the benefits of the m-sequence and proposed a method to adapt the generation of the m-sequence for use in the newly proposed scheme. We also derived the ETTR mathematically for the new scheme with the m-sequence and showed through simulations that the performance of the new scheme with the m-sequence is superior to that of the conventional scheme with the m-sequence. Notably, when there is only one common channel, the new scheme with the m-sequence achieved approximately four times the improvement in the ETTR compared to the conventional scheme.

The nuclear industry uses 304L stainless steel to construct canisters for storing spent nuclear fuel. The spent nuclear fuel canisters require the lifetime prediction and robustness of their corrosion behavior over periods ranging from thousands to hundreds of thousands of years. Since nuclear power plants are predominantly located in coastal areas, where storage conditions are highly vulnerable to chloride environments, extensive research has been conducted to enhance the canisters’ stress corrosion cracking (SCC) resistance. The welded canisters inherently possess residual tensile stress, prompting the application of plastic deformation-based techniques to boost their SCC resistance, with peening being the most prevalent method. It is reported that UNSM increases the SCC resistance by plastic deformation through surface treatment. In this study, the commercial 304L stainless steel was subjected to UNSM treatment on base metal, heat affected zone (HAZ), and weld metal U-bend test specimens to induce compressive residual stresses up to a depth of 1 mm. The impact of peening treatment on SCC properties was explored through microstructural analysis, corrosion properties analysis, and compressive residual stress assessments. The U-bend specimens underwent SCC testing (in 42% MgCl2 at 155 °C), microstructure examination using an optical microscope (OM) and a scanning electron microscope (SEM), electron backscatter diffraction (EBSD) analysis, and compressive residual stress measurements via the hole-drilling method. Corrosion behavior on the surface and cross-section was evaluated using anodic polarization tests, electrochemical impedance spectroscopy (EIS) measurements, double loop-electrochemical potentiokinetic reactivation (DL-EPR) tests, and ASTM A262 Pr. C tests. The compressive residual stress imparted by UNSM refined the outermost grains of the cross-section and enhanced the corrosion resistance of 304L stainless steel. Furthermore, it led to a longer crack initiation time, a reduced crack propagation rate, and improved SCC properties.

Stainless steel is widely used in various industrial fields due to its excellent corrosion resistance and mechanical properties. The key to this corrosion resistance is the thin passive film that naturally forms on the metal surface. Passive films are characterized by oxide film theory and adsorption theory, each uniquely explaining the structure and mechanism of the protective film on the metal surface. Research on the semiconductive properties of passive films on stainless steel offers diverse viewpoints, classifying theories into the point defect model and the bipolar fixed charge-induced passivity. Specific changes in passive film attributes that lead to degradation, however, are not fully understood. In this study, we analyzed the inner and outer layers of the passive film on super austenitic stainless steel SR-50A under various conditions in acidic and alkaline chloride environments. The interpretations of these results were based on the point defect model and the bipolar model for the passivation mechanism, and correlations between p-type and n-type semiconductor properties and passivation behavior were examined. The surface of the stainless steel forms a passive film comprising two layers with p-type and n-type semiconductive properties, independent of the pH of the solutions. The corrosion resistance increases as the p-type and n-type semiconductive tendencies become more balanced, consequently enhancing the properties of the passive film.

HT074, a multiherbal mixture containing extracts from Inula britannica flowers and Paeonia lactiflora roots, is used in Korean medicine for gastric disorders. This study investigated the protective mechanisms of HT074 against acute reflux esophagitis (RE) in rats. Nitric oxide (NO) production and mRNA expression of antioxidant-related genes (Nrf2, HO-1, SOD, CAT, and GPx2) were evaluated in LPS-induced RAW 264.7 cells. Gastroesophageal reflux (GER) was induced in rats, followed by HT074 (100, 300 mg/kg) or ranitidine (50 mg/kg) administration. Esophageal damage and histological changes were assessed. Gastric pH and protein expression levels of Nrf2, HO-1, SOD, CAT, and GPx-1/2 were measured. HT074 pretreatment reduced NO production and increased the expression of HO-1, CAT, and GPx2 in LPS-induced RAW 264.7 cells. In GER-induced rats, HT074 significantly decreased esophageal lesions and increased the expression of HO-1, SOD, GPx-1/2, and Nrf2. HT074 did not affect gastric pH. These findings suggest that HT074 protects against GER-induced esophagitis by inhibiting NO production and enhancing antioxidant activity. Therefore, HT074 could be a promising therapeutic agent for GER disease.

Austenitic stainless steels used in structural applications suffer from stress corrosion cracking due to residual stresses during welding. Much research is being conducted to prevent the stress corrosion cracking of austenitic steels by inducing compressive residual stresses. One method is ultrasonic shot peening (USP), which is used to apply compressive stress by modifying the mechanical properties of the material’s surface. In this study, 304L stainless steel was butt-welded by gas tungsten arc welding (GTAW) and subsequently subjected to compressive residual stress to a depth of 1 mm from the surface by a USP treatment. The influence of USP on microstructural changes in the base metal, the HAZ and weldment, and the corrosion properties was analyzed. A microstructural analysis was conducted using SEM-EDS, XRD, and EBSD methods alongside residual stress measurements. The surface and cross-sectional corrosion behavior was evaluated and analyzed using a potentiodynamic polarization test, electrochemical impedance spectroscopy (EIS) measurements, a double-loop electrochemical potentiokinetic reactivation (DL-EPR) test, and an ASTM A262 Pr. C test. The surface was deformed and roughened by the USP. The deformed areas formed crevices, and the inside of the crevices contained some cracks. The crevices and internal cracks caused pitting, which reduced the resistance of the passivation film. The cross-section was subjected to compressive residual stress to a depth of 1 mm from the surface, and the outermost area of the cross-section had fine grain refinement, forming a solid passivation film that improved the corrosion resistance.

As cloud computing and AI as a Service are provided, it is increasingly necessary to deal with privacy sensitive data. To deal with the sensitive data, there are two cases of outsourcing process: i) many clients participate dynamically ii) many clients are pre-determined. The solutions for protecting sensitive data in both cases are the multi-key homomorphic encryption (MKHE) scheme and the threshold multi-key homomorphic encryption (TMKHE) scheme. However, these schemes may be difficult for clients with limited resources to perform MKHE and TMKHE. In addition, due to the large size of the evaluation keys, in particular multiplication and rotation keys, the communication between the clients and server that provide outsourcing service increases. Also, the size of the evaluation keys that the server must hold is tremendous, in particular, for the multiplication and rotation keys, which are essential for bootstrapping operation. In this paper, we propose a variant of MKHE and TMKHE with reduced evaluation keys. To reduce the size of the evaluation keys, we propose a variant of ring learning with errors (RLWE), called RLWE reusing errors (ReRLWE). ReRLWE generates other components by reusing the error that is used when generating an RLWE sample. We prove that RLWE can be reduced to ReRLWE and propose modified evaluation keys under the ReRLWE assumption, which are the modified multiplication and rotation keys. For MKHE, multiplication and rotation keys are reduced by 66% and 25%, respectively. For TMKHE, a multiplication and rotation keys are reduced by 50% and 25%, respectively.

Homomorphic encryption (HE) is one of the representative solutions to privacy-preserving machine learning (PPML) classification enabling the server to classify private data of clients while guaranteeing privacy. This work focuses on PPML using word-wise fully homomorphic encryption (FHE). In order to implement deep learning on word-wise HE, the ReLU and max-pooling functions should be approximated by polynomials for homomorphic operations. Most of the previous studies focus on HE-friendly networks, which approximate the ReLU and max-pooling functions using low-degree polynomials. However, this approximation cannot support deeper neural networks due to large approximation errors in general and can classify only relatively small datasets. Thus, we propose a precise polynomial approximation technique, a composition of minimax approximate polynomials of low degrees for the ReLU and max-pooling functions. If we replace the ReLU and max-pooling functions with the proposed approximate polynomials, standard deep learning models such as ResNet and VGGNet can still be used without further modification for PPML on FHE. Even pre-trained parameters can be used without retraining, which makes the proposed method more practical. We approximate the ReLU and max-pooling functions in the ResNet-152 using the composition of minimax approximate polynomials of degrees 15, 27, and 29. Then, we succeed in classifying the plaintext ImageNet dataset with 77.52% accuracy, which is very close to the original model accuracy of 78.31%. Also, we obtain an accuracy of 87.90% for classifying the encrypted CIFAR-10 dataset in the ResNet-20 without any additional training.

Driver behavior features extracted from the controller area network (CAN) have potential applications in improving vehicle safety. However, the development of a classifier-based intrusion detection system (IDS) for in-vehicle networks remains an open research problem. To address this challenge, we incorporate novel $n$ -fold cross-validation windowing techniques on two publicly available driving behavior datasets. A driver classification-based IDS is proposed using the LSTM-FCN model that utilizes the strengths of both fully convolutional network (FCN) and long short-term memory (LSTM) networks. These modules allow the model to learn spatial and temporal features and utilize contextual information. In addition, we combine three squeeze and excite (SnE) layers following FCN layers to incorporate adjacent spatial locations and augment a scaled dot product attention mechanism into the LSTM to improve its feature selection and extraction capabilities. Our proposed IDS uses hacking and countermeasure research lab (HCRL) and test datasets, which achieve an improvement in accuracy of 4.18% and 13.99% respectively, from the baseline LSTM-FCN model. The experimental results of our method exhibited an overall accuracy of 99.36% and 96.36% for both datasets and outperformed various state-of-the-art methods.

In Internet of Things (IoT) environments, effective public key management is crucial for managing numerous devices. RF features, primarily considered analog features within physical layer authentication by RF Fingerprinting (RFF) processes, present a novel approach to key management. In this research, we introduce a novel RF-based Public Key Generator (RF-PubKG) model that maps RF features into cryptographic sequences by incorporating a Key Generation (KeyGen) layer into the RFF model. The RF-PubKG demonstrates superior performance, achieving 97.2% accuracy at a 20dB SNR and further improving to 99.6% in noise-free conditions with a Frame Error Rate (FER) below 1%. The generated public key sets exhibit negligible correlation, with intra-key-set correlations not exceeding 0.24 and inter-model correlations falling below 0.04, highlighting the reliability of the RF-PubKG model. The integration with the Rivest–Shamir–Adleman (RSA) algorithm provides proof-of-concept for the RF-PubKG-based digital signature scheme, effectively simplifying the Certificate Authorities (CAs) management and, consequently, reducing Public Key Infrastructure (PKI) complexity. This simplification promises effective public key management within the Public Key Cryptography (PKC), thereby enhancing the efficiency of digital signature verification processes.

Abstract Until recent, there are no ideal small diameter vascular grafts available on the market. Most of the commercialized vascular grafts are used for medium to large-sized blood vessels. As a solution, vascular tissue engineering has been introduced and shown promising outcomes. Despite these optimistic results, there are limitations to commercialization. This review will cover the need for extrusion-based 3D cell-printing technique capable of mimicking the natural structure of the blood vessel. First, we will highlight the physiological structure of the blood vessel as well as the requirements for an ideal vascular graft. Then, the essential factors of 3D cell-printing including bioink, and cell-printing system will be discussed. Afterwards, we will mention their applications in the fabrication of tissue engineered vascular grafts. Finally, conclusions and future perspectives will be discussed.

Abstract Background The incidence of inflammatory bowel disease (IBD), an inflammatory disorder of the gastrointestinal system has increased. IBD, characterized by aberrant immune responses against antigens, is thought to be caused by the invasion of enterobacteria. The pathogenesis of IBD is complicated, hence novel effective therapeutic agents are warranted. Therefore, this study evaluates the potential of Artemisia argyi, a medicinal herb, in alleviating IBD. Methods The effectiveness of the A. argyi ethanol extract was verified both in vitro and in vivo. Inflammation was induced in RAW 264.7 cells by 1 μg/mL of lipopolysaccharide (LPS) and by 3% dextran sodium sulfate (DSS) in a DSS-induced colitis mouse model. During the ten-day colitis induction, 200 mg/kg of A. argyi ethanol extract was orally administered to the treatment group. Levels of inflammation-related proteins and genes were analyzed in the colon, serum, and lymphoid tissues, i.e., Peyer’s patches (PPs) and spleen. The chemical constituent of the A. argyi ethanol extract was identified using an ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis. Results A. argyi ethanol extract treatment ameliorated IBD symptoms and reduced the expression of inflammation-related proteins and genes in the colon and serum samples. Furthermore, A. argyi treatment induced the activation of anti-oxidative associated proteins, such as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); and the treatment have also inhibited nuclear factor-κB (NF-κB), a central mediator of inflammatory responses. A. argyi enhanced the immunomodulatory effects in the PPs and spleen, which may stem from interleukin-10 (IL-10) upregulation. Chemical analysis identified a total of 28 chemical compounds, several of which have been reported to exert anti-inflammatory effects. Conclusions The effectiveness of the A. argyi ethanol extract in alleviating IBD was demonstrated; application of the extract successfully mitigated IBD symptoms, and enhanced immunomodulatory responses in lymphoid tissues. These findings suggest A. argyi as a promising herbal medicine for IBD treatment.

Fully homomorphic encryption (FHE) is a prospective tool for privacy-preserving machine learning (PPML). Several PPML models have been proposed based on various FHE schemes and approaches. Although FHE schemes are suitable as tools for implementing PPML models, previous PPML models based on FHE, such as CryptoNet, SEALion, and CryptoDL, are limited to simple and nonstandard types of machine learning models; they have not proven to be efficient and accurate with more practical and advanced datasets. Previous PPML schemes replaced non-arithmetic activation functions with simple arithmetic functions instead of adopting approximation methods and did not use bootstrapping, which enables continuous homomorphic evaluations. Thus, they could neither use standard activation functions nor employ large numbers of layers. In this work, we first implement the standard ResNet-20 model with the RNS-CKKS FHE with bootstrapping and verify the implemented model with the CIFAR-10 dataset and plaintext model parameters. Instead of replacing the non-arithmetic functions with simple arithmetic functions, we use state-of-the-art approximation methods to evaluate these non-arithmetic functions, such as ReLU and Softmax, with sufficient precision. Further, for the first time, we use the bootstrapping technique of the RNS-CKKS scheme in the proposed model, which enables us to evaluate an arbitrary deep learning model on encrypted data. We numerically verify that the proposed model with the CIFAR-10 dataset shows 98.43% identical results to the original ResNet-20 model with non-encrypted data. The classification accuracy of the proposed model is 92.43%±2.65%, which is quite close to that of the original ResNet-20 CNN model (91.89%). It takes approximately 3 h for inference on a dual Intel Xeon Platinum 8280 CPU (112 cores) with 172 GB of memory. We believe that this opens the possibility of applying FHE to an advanced deep PPML model.

The sign function can be adopted to implement the comparison operation, max function, and rectified linear unit (ReLU) function in the Cheon–Kim–Kim–Song (CKKS) scheme; hence, several studies have been conducted to efficiently evaluate the sign function in the CKKS scheme. Recently, Lee et al. (IEEE Trans. Depend. Sec. Comp.) proposed a practically optimal approximation method for the sign function in the CKKS scheme using a composition of minimax approximate polynomials. In addition, Lee et al. proposed a polynomial-time algorithm that finds the degrees of component polynomials that minimize the number of non-scalar multiplications. However, homomorphic comparison/max/ReLU functions using Lee et al.’s approximation method have not been successfully implemented in the residue number system variant CKKS (RNS-CKKS) scheme. In addition, the degrees of component polynomials found by Lee et al.’s algorithm are not optimized for the RNS-CKKS scheme because the algorithm does not consider that the running time of non-scalar multiplication depends significantly on the ciphertext level in the RNS-CKKS scheme. In this study, we propose a fast algorithm for the inverse minimax approximation error, which is a subroutine required to find the optimal set of degrees of component polynomials. The proposed algorithm facilitates determining the optimal set of degrees of component polynomials with higher degrees than in the previous study. In addition, we propose a method to find the degrees of component polynomials optimized for the RNS-CKKS scheme using the proposed algorithm for the inverse minimax approximation error. We successfully implement the homomorphic comparison, max function, and ReLU function algorithms on the RNS-CKKS scheme with a low comparison failure rate ( $< 2^{-15}$ ), and provide various parameter sets according to the precision parameter $\alpha $ . We reduce the depth consumption of the homomorphic comparison, max function, and ReLU function algorithms by one depth for several values of $\alpha $ . In addition, the numerical analysis demonstrates that the homomorphic comparison, max function, and ReLU function algorithms using the degrees of component polynomials found by the proposed algorithm reduce the running time by 6%, 7%, and 6% on average, respectively, compared with those using the degrees of component polynomials found by Lee et al.’s algorithm.

Abstract Background We investigated the associations between fasting glucose level ranges with lifestyle factors and metabolic profiles among adults without previous diagnosis of diabetes. Methods We analyzed 13 625 adults without previous diagnosis of diabetes from the Korea National Health and Nutrition Examination Survey during 2016 to 2018. We categorized fasting glucose levels (mg/dl) as follows:

Activated stellate cells play a role in fibrosis development in the liver, pancreas, and kidneys. The fusion protein R-III, which consists of retinol-binding protein and albumin domain III, has been demonstrated to attenuate liver and renal fibrosis by suppressing stellate cell activation. In this study, we investigated the efficacy of R-III against bleomycin-induced lung fibrosis in mice. R-III reduced lung fibrosis and primarily localized in autofluorescent cells in the lung tissue. Furthermore, we isolated lung stellate cells (LSCs) from rat lungs using the isolation protocol employed for hepatic stellate cells (HSCs). LSCs shared many characteristics with HSCs, including the presence of vitamin A-containing lipid droplets and the expression of alpha-smooth muscle actin and collagen type I, markers for activated HSCs/myofibroblasts. LSCs spontaneously transdifferentiated into myofibroblasts in in vitro culture, which was inhibited by R-III. These findings suggest that R-III may reduce lung fibrosis by inactivating LSCs and could be a promising treatment for extrahepatic fibrosis.

Abstract The effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.

Abstract Cell surface heparan sulfate proteoglycan (HSPG)-mediated endocytosis results in poor yields of recombinant human bone morphogenetic proteins (rhBMPs) from CHO cell cultures. Upon incubation of rhBMP-2 and rhBMP-7 with CHO cells at 37 °C, both rhBMP-2 and rhBMP-7 bound to the cell surface HSPGs in CHO cells, but only rhBMP-2 was actively internalized into CHO cells. Cell surface HSPGs were found to serve as the main receptor for rhBMP-2 internalization. It was also found that the cell surface HSPG-mediated endocytosis of rhBMP-2 occurred through both the clathrin- and caveolin-dependent pathways. Blockage of rhBMP-2 internalization by the addition of structural analogs of HSPGs such as dextran sulfate (DS) and heparin dramatically increased rhBMP-2 production in recombinant CHO (rCHO) cell cultures. Compared to the control cultures, addition of DS (1.0 g/L) and heparin (0.2 g/L) resulted in a 22.0- and 19.0-fold increase in the maximum rhBMP-2 concentration, respectively. In contrast, the production of rhBMP-7, which was not internalized into the rCHO cells, did not dramatically increase upon addition of DS and heparin. Taken together, rhBMPs have a different fate in terms of HSPG-mediated internalization in CHO cells. HSPG-mediated endocytosis of each rhBMP should be understood individually to increase the rhBMP yield in rCHO cell cultures.

Introduction Through the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), we compared the pandemic impact on the volume of primary care visits and uptake of virtual care in Australia, Canada, China, Norway, Singapore, South Korea, Sweden, the UK and the USA.Methods Visit definitions were agreed on centrally, implemented locally across the various settings in INTRePID countries, and weekly visit counts were shared centrally for analysis. We evaluated the weekly rate of primary care physician visits during 2019 and 2020. Rate ratios (RRs) of total weekly visit volume and the proportion of weekly visits that were virtual in the pandemic period in 2020 compared with the same prepandemic period in 2019 were calculated.Results In 2019 and 2020, there were 80 889 386 primary care physician visits across INTRePID. During the pandemic, average weekly visit volume dropped in China, Singapore, South Korea, and the USA but was stable overall in Australia (RR 0.98 (95% CI 0.92 to 1.05, p=0.59)), Canada (RR 0.96 (95% CI 0.89 to 1.03, p=0.24)), Norway (RR 1.01 (95% CI 0.88 to 1.17, p=0.85)), Sweden (RR 0.91 (95% CI 0.79 to 1.06, p=0.22)) and the UK (RR 0.86 (95% CI 0.72 to 1.03, p=0.11)). In countries that had negligible virtual care prepandemic, the proportion of visits that were virtual were highest in Canada (77.0%) and Australia (41.8%). In Norway (RR 8.23 (95% CI 5.30 to 12.78, p

In this paper, we propose various quantitative information-theoretic bit security reduction measures that correlate the statistical difference between two probability distributions with the security level gap for two cryptographic schemes. We derive tighter relations between information-theoretic measures for quantifying the precision and guarantee the security level of the cryptographic scheme implemented over a precision-restricted environment. Further, the generalized versions of previous security reductions are devised by relaxing the constraints on the upper bounds of the information-theoretic measures. This makes it possible to estimate bit security more reliable and improves the security level. We also estimate the effects on the security level when the $\kappa $ -bit secure original scheme is implemented on a $p$ -bit precision system. In previous studies, $p$ was fixed as $\frac {\kappa }2$ ; however, the proposed schemes are generalized such that the security level $\kappa $ and precision $p$ can vary independently. This results in a significant difference. Moreover, previous results cannot provide the exact lower bound of the security level for $p\ne {\frac {\kappa }{2}}$ . However, the proposed results can provide the exact lower bound of the estimation value of the security level as long as the precision $p$ satisfies certain conditions. We provide diverse types of security reduction formulas for the six types of information-theoretic measures. The proposed schemes can provide information-theoretic guidelines regarding the difference between the security levels of two identical cryptographic schemes when extracting randomness from two different probability distributions. In particular, the proposed schemes can be used to quantitatively estimate the effect of the statistical difference between the ideal and real distributions on the security level.

The Shell sort algorithm is one of the most practically effective in-place sorting algorithms. However, it is difficult to execute this algorithm with its intended running time complexity on data encrypted using fully homomorphic encryption (FHE), because the insertion sort in Shell sort has to be performed by considering the worst-case input data. In this paper, in order for the sorting algorithm to be used on the FHE data, we modify the Shell sort with an additional parameter $\alpha $ , allowing exponentially small sorting failure probability. For a gap sequence of powers of two, the modified Shell sort with input array length $n$ is found to have the trade-off between the running time complexity of $O(n^{3/2}\sqrt {\alpha +\log \log n})$ and the sorting failure probability of $2^{-\alpha }$ . Its running time complexity is close to the intended running time complexity of $O(n^{3/2})$ and the sorting failure probability can be made very low with slightly increased running time. Further, the near-optimal window length of the modified Shell sort is also derived via convex optimization. The proposed analysis of the modified Shell sort is numerically confirmed by using randomly generated arrays. For the practical aspect, our modification can be applied to any gap sequence, and we show that Ciura’s gap sequence, which is known to have good practical performance, is also practically effective when our modified Shell sort is applied. We compare our modified Shell sort with other sorting algorithms with the FHE over the torus (TFHE) library, and it is shown that this modified Shell sort has the best performance in running time among in-place sorting algorithms on homomorphic encryption scheme.

Many lattice-based cryptographic schemes are constructed based on hard problems on an algebraic structured lattice, such as the short integer solution (SIS) problems. These problems are called ring-SIS (R-SIS) and its generalized version, module-SIS (M-SIS). Generally, it has been considered that problems defined on the module lattice are more difficult than the problems defined on the ideal lattice. However, Koo, No, and Kim showed that R-SIS is more difficult than M-SIS under some norm constraints of R-SIS. However, this reduction has problems in that the rank of the module is limited to about half of the instances of R-SIS, and the comparison is not performed through the same modulus of R-SIS and M-SIS. In this paper, we propose the three reductions. First, we show that R-SIS is more difficult than M-SIS with the same modulus and ring dimension under some constraints of R-SIS. Also, we show that through the reduction from M-SIS to R-SIS with the same modulus, the rank of the module is extended as much as the number of instances of R-SIS from half of the number of instances of R-SIS compared to the previous work. Second, we show that R-SIS is more difficult than M-SIS under some constraints, which is tighter than the M-SIS in the previous work. Finally, we propose that M-SIS with the modulus prime $q^{k}$ is more difficult than M-SIS with the composite modulus $c$ , such that $c$ is divided by $q$ . Through the three reductions, we conclude that R-SIS with the modulus $q$ is more difficult than M-SIS with the composite modulus $c$ .

Abstract Background The roots of Pueraria lobata and Scutellaria baicalensis, herbal medicines with a long history of widespread use, have been traditionally prescribed in combination to treat stroke, diabetes, and acute infectious diarrhea in East Asia. Nevertheless, toxicological data on these herbs and their combination are limited. This study investigated the acute and 13-week subchronic toxicity of root extract of P. lobata and S. baicalensis (HT047) for stroke treatment in male and female Sprague-Dawley rats. Methods In the acute toxicity study, HT047 was administered orally at a single dose of 5000 mg/kg. In the subchronic toxicity study, HT047 was administered orally at repeated daily doses of 800, 2000, and 5000 mg/kg/day for 13 weeks, followed by a 4-week recovery period. Results In the acute toxicity study, there were no deaths or toxicologically significant changes in clinical signs, body weight, and necropsy findings. In the subchronic toxicity study, HT047 at all doses caused no death and no treatment-related adverse effects on food consumption; organ weight; ophthalmologic, urinalysis, and hematological parameters; and necropsy findings of both rat sexes. There were some treatment-related alterations in clinical signs, body weight, and serum biochemistry and histopathological parameters; however, these changes were not considered toxicologically significant because they were resolved during the recovery period or resulted from the pharmacological effects of P. lobata and S. baicalensis. Conclusions The oral approximate lethal dose (the lowest dose that causes mortality) of HT047 was greater than 5000 mg/kg in male and female rats. The oral no-observed-adverse-effect level of HT047 was greater than 5000 mg/kg/day in rats of both sexes, and no target organs were identified. The present findings support the safety of an herbal extract of P. lobata and S. baicalensis as a therapeutic agent for stroke and further confirm the safety of the combined use of P. lobata and S. baicalensis in clinical practice.

Storage canisters used in nuclear power plants operating in seaside areas—where the salt content in the atmosphere is high—may be susceptible to chloride-induced stress corrosion cracking (CISCC). Chloride-induced stress corrosion cracking is one of the ways in which dry storage canisters made of stainless steel can degrade. Stress corrosion cracking depends on the microstructure and residual stress, and it is therefore very important to improve the surface properties of materials. Laser shock peening both greatly deforms the material surface and refines grains, and it generates compressive residual stress in the deep part from the surface of the material. This study focused on the effect of laser shock peening on the stress corrosion cracking of 304L stainless steel. The laser shock peening was found to induce compressive residual stress from the surface to a 1 mm depth, and the SCC properties were evaluated by a U-bend test. The results showed that the SCC resistance of laser-peened 304L stainless steel in a chloride environment was enhanced, and that it was closely related to grain size, the pitting potential of the cross section, and residual stress.

For in-vehicle network communication, the controller area network (CAN) broadcasts to all connected nodes without address validation. Therefore, it is highly vulnerable to all sorts of attack scenarios. This research proposes a novel intrusion detection system (IDS) for CAN to identify in-vehicle network anomalies. The statistical characteristics of attacks provide valuable information about the inherent intrusion patterns and behaviors. We employed two real-world attack scenarios from publicly available datasets to record a real-time response against intrusions with increased precision for in-vehicle network environments. Our proposed IDS can exploit malicious patterns by calculating thresholds and using the statistical properties of attacks, making attack detection more efficient. The optimized threshold value is calculated using brute-force optimization for various window sizes to minimize the total error. The reference values of normality require a few legitimate data frames for effective intrusion detection. The experimental findings validate that our suggested method can efficiently detect fuzzy, merge, and denial-of-service (DoS) attacks with low false-positive rates. It is also demonstrated that the total error decreases with an increasing attack rate for varying window sizes. The results indicate that our proposed IDS minimizes the misclassification rate and is hence better suited for in-vehicle networks.

Pseudogymnoascus is a psychrophilic fungus, which is a genus widely distributed in cold regions around the world. Recently, the presence of Pseudogymnoascus destructans (Pd), the causative agent of white-nose syndrome (WNS) belonging to Pseudogymnoascus, has been reported in neighboring countries of Korea. However, no investigation on Pd has been reported in Korea. In this study, cave-inhabiting bats and their habitats were investigated in terms of the diversity of cave fungi, and we tried to confirm the presence of Pd. Three caves suspected of hosting Pd were selected, and 83 environmental and 53 bat samples were collected. A total of 154 fungal strains belonging to 31 different genera were isolated, and 20 of 154 were confirmed to belong to Pseudogymnoascus. Pd-diagnostic PCR was performed to check whether Pd was present in the isolated Pseudogymnoascus, and seven positives were confirmed. However, phylogenetic analyses revealed that no isolates belonged or were closely related to the clade with Pd. Although samples were collected from limited areas, undescribed Pseudogymnoascus species were isolated, and it was confirmed that Korean isolates were distributed in various clades. In conclusion, it is hypothesized that Korean Pseudogymnoascus presents high diversity.

The inner shell of the chestnut (Castanea crenata) has long been used in Asia as a medicinal herb for improving digestion and blood circulation, and treating diarrhea. However, most chestnut shells are now treated as waste materials in industrial peeling processes. In this study, we examined the metabolite variation among major cultivars of C. crenata shells using mass spectrometry. Among five representative cultivars, Okkwang, Porotan, and Ishizuuchi had higher levels of bioactive compounds, such as ellagic acid derivatives, ellagitannins, flavonoids, and gallic acid derivatives. Their antioxidant capacity was positively correlated with their chemical composition. The byproducts (whole shells) from the industrial peeling process were re-evaluated in comparison with the inner shell, a rich source of phenolic compounds. The phenolic acids and flavonoid glucoside derivatives were significantly higher in the whole shells, whereas the levels of flavonoids were higher in the inner shells. In addition, the whole shell extracts significantly reduced cellular reactive oxygen species production compared to the inner shell extracts. This study demonstrated the different biochemical benefits of different C. crenata cultivars through metabolic profiling and suggests that the whole shell could be used as a functional ingredient, as it has the highest levels of bioactive products and antioxidant effects.

Lattice-based cryptographic scheme is constructed based on hard problems on a lattice such as the short integer solution (SIS) problem and the learning with error (LWE). However, the cryptographic scheme based on SIS or LWE is inefficient since the size of the key is too large. Thus, most cryptographic schemes use the variants of LWE and SIS with ring and module structures. Albrecht and Deo showed that there is a reduction from module-LWE (M-LWE) to ring-LWE (R-LWE) in the polynomial ring by handling the error rate and modulus. However, unlike the LWE problem, the SIS problem does not have an error rate, but there is the upper bound β on the norm of the solution of the SIS problem. In this paper, we propose the two novel reductions related to module-SIS (M-SIS) and ring-SIS (R-SIS) on a polynomial ring. We propose (i) the reduction from R-SIS qk,mk,βk to R-SISq,m,β and (ii) the reduction from M-SIS to R-SIS under norm constraint of R-SIS. Combining these two results implies that R-SIS for a specified modulus and number samples is more difficult than M-SIS under norm constraints of R-SIS, which provides the range of possible module ranks for M-SIS. From the reduction we propose, contrary to the widely known belief, our result shows that there is a possibility that the security parameters of M-SIS may be less secure when it reduces to R-SIS for the theoretical reasons presented in this paper. Therefore, when generating parameters on an M-SIS structure, the theoretical security level over R-SIS also should also be checked at the same time.

Among many submissions to NIST post-quantum cryptography (PQC) project, NewHope is a promising key encapsulation mechanism (KEM) based on the Ring-Learning with errors (Ring-LWE) problem. Since NewHope is an indistinguishability (IND)-chosen ciphertext attack secure KEM by applying the Fujisaki-Okamoto transform to an IND-chosen plaintext attack secure public-key encryption, accurate calculation of decryption failure rate (DFR) is required to guarantee resilience against attacks that exploit decryption failures. However, the current upper bound (UB) on DFR of NewHope is rather loose because the compression noise, the effect of encoding/decoding of NewHope, and the approximation effect of centered binomial distribution are not fully considered. Furthermore, since NewHope is a Ring-LWE based cryptography, there is a problem of error dependency among error coefficients, which makes accurate DFR calculation difficult. In this paper, we derive much tighter UB on DFR than the current UB by using constraint relaxation and union bound. Especially, the above-mentioned factors are all considered in the derivation of new UB and the centered binomial distribution is not approximated. Since the error dependency is also considered, the new UB is much closer to the real DFR than the current UB. Furthermore, the new UB is parameterized by using Chernoff-Cramer bound to facilitate the calculation of new UB for the parameters of NewHope. Since the new UB is much lower than the DFR requirement of PQC, this DFR margin can be used to improve NewHope. As a result, the security level and bandwidth efficiency of NewHope are improved by 7.2 % and 5.9 %, respectively.

We present a novel code-based signature scheme called modified pqsigRM. This scheme is based on a modified Reed-Muller (RM) code, which reduces the signing complexity and key size compared with existing code-based signature schemes. In fact, it strengthens pqsigRM submitted to NIST for post-quantum cryptography standardization. The proposed scheme has the advantage of the pqsigRM decoder and uses public codes that are more difficult to distinguish from random codes. We use (U, U + V)-codes with the high-dimensional hull to overcome the disadvantages of code-based schemes. The proposed decoder samples from coset elements with small Hamming weight for any given syndrome and efficiently finds such an element. Using a modified RM code, the proposed signature scheme resists various known attacks on RM-code-based cryptography. For 128 bits of classical security, the signature size is 4096 bits, and the public key size is less than 1 MB.

With the ongoing developments in artificial intelligence (AI), big data, and cloud services, fully homomorphic encryption (FHE) is being considered as a solution for preserving the privacy and security in machine learning systems. Currently, the existing FHE schemes are constructed using lattice-based cryptography. In state-of-the-art algorithms, a huge amount of computational resources are required for homomorphic multiplications and the corresponding bootstrapping that is necessary to refresh the ciphertext for a larger number of operations. Therefore, it is necessary to discover a new innovative approach for FHE that can reduce the computational complexity for practical applications. In this paper, we propose a code-based homomorphic operation scheme. Linear codes are closed under the addition, however, achieving multiplicative homomorphic operations with linear codes has been impossible until now. We strive to solve this problem by proposing a fully homomorphic code scheme that can support both addition and multiplication simultaneously using the Reed-Muller (RM) codes. This can be considered as a preceding step for constructing code-based FHE schemes. As the order of RM codes increases after multiplication, a bootstrapping technique is required to reduce the order of intermediate RM codes to accomplish a large number of operations. We propose a bootstrapping technique to preserve the order of RM codes after the addition or multiplication by proposing three consecutive transformations that create a one-to-one relationship between computations on messages and that on the corresponding codewords in RM codes.

Since Cheon et al. introduced an approximate homomorphic encryption scheme for complex numbers called Cheon-Kim-Kim-Song (CKKS) scheme, it has been widely used and applied in real-life situations, such as privacy-preserving machine learning. The polynomial approximation of a modulus reduction is the most difficult part of the bootstrapping for the CKKS scheme. In this article, we cast the problem of finding an approximate polynomial for a modulus reduction into an L2-norm minimization problem. As a result, we find an approximate polynomial for the modulus reduction without using the sine function, which is the upper bound for the approximation of the modulus reduction. With the proposed method, we can reduce the degree of the polynomial required for an approximate modulus reduction, while also reducing the error compared with the most recent result reported by Han et al. (CT-RSA’ 20). Consequently, we can achieve a low-error approximation, such that the maximum error is less than 2−40 for the size of the message $m/q\approx 2^{-10}$ . By using the proposed method, the constraint of $q = \mathcal {O}(m^{3/2})$ is relaxed as $\mathcal {O}(m)$ , and thus the level loss in bootstrapping can be reduced. The solution to the cast problem is determined in an efficient manner without iteration.

White-nose syndrome (WNS), caused by Pseudogymnoascus destructans (Pd), is a lethal fungal disease that affects hibernating bats in North America. Recently, the presence of Pd was reported in countries neighboring Korea. However, Pd has not been investigated in Korea. Therefore, this study aimed to identify the presence of Pd in Korean bats. Altogether, wings from 241 bats were collected from 13 cities and cultured. A total of 79 fungal colonies were isolated, and two isolates were identified as Pd using polymerase chain reaction. Of the nine bat species captured in 13 cities, Pd was isolated only from Myotis petax in Goryeong. Atypical, curved conidia were observed in two isolated fungal colonies. Although histological lesions were not observed by hematoxylin and eosin or periodic acid–Schiff staining, fungal invasion was observed in the tissue sections. Taken together, these results confirmed the presence of Pd in Korean bats and suggest the possibility of WNS outbreaks in Korean bats. This is the first report of the isolation and molecular analysis of Pd from Korean bats.

Adenovirus has been detected in a wide range of hosts like dogs, foxes, horses, bats, avian animals, and raccoon dogs. Canine adenoviruses with two serotypes host mammals and are members of the mastadenovirus family. Canine adenovirus type 1 (CAdV-1) and canine adenovirus type 2 (CAdV-2) cause infectious canine hepatitis and infectious bronchial disease, respectively. In this study, we investigated the prevalence of CAdV-1 and 2 in wild Nyctereutes procyonoides in Korea in 2017–2020 from 414 tissue samples, including the liver, kidney, lung, and intestine, collected from 105 raccoon dog carcasses. Only CAdV-2 was detected in two raccoon dogs, whereas CAdV-1 was not detected. Tissue samples from raccoon dogs were screened for CAdV-1 and CAdV-2 using conventional PCR. Adenovirus was successfully isolated from PCR positive samples using the Vero cell line, and the full-length gene sequence of the isolated viruses was obtained through 5’ and 3’ rapid amplification of cDNA ends (RACE). The major genes of the isolated CAdV-2/18Ra54 and CAdV-2/18Ra-65 strains showed the closest relationship with that of the CAdV-2 Toronto A26/61 strain isolated from Canada in 1976. There is no large mutation between CAdV-2, which is prevalent worldwide, and CAdV-2, which is prevalent in wild animals in Korea. In addition, it is still spreading and causing infections. The Toronto A26/61 strain, which showed the most similarity to CAdV-2/18Ra-54, was likely transmitted to wild animals through vaccinated companion animals, suggesting that further research is needed on safety measures surrounding animal vaccination. This study provides information on the genetic characteristics and prevalence of canine adenovirus in domestic wild animals and provides a better understanding of canine adenovirus.

This paper makes two major contributions. First, we propose an algorithm to compute a multiplicative inverse modulo $2^{k}$ without using integer division by refining the Arazi–Qi algorithm. We then generalize this algorithm into a scalable algorithm to compute an inverse modulo $2^{kl}$ by iteratively exploiting a $k$ -bit-based process when the inverse modulo $2^{k}$ is given. Because of its scalability, this generalized algorithm can be cost-effectively implemented on hardware and applied to larger modulus operations by iteratively applying a processing unit. Furthermore, we highlight the possibility of the derivation of a binary representation of an inverse $P^{-1}$ in terms of a representation of $P$ and demonstrate this operation for up to eight bits. Second, using this direct relationship, we propose a multi-bit Montgomery inverse algorithm that is at least three times faster than the original version. Finally, we derive various properties of this algorithm and compare it with previous algorithms. This fast calculation of a Montgomery inverse is important for public key cryptographic applications, such as elliptic curve cryptosystems, because the relative speed of calculating a modular inverse for modular multiplication is a critical parameter for deciding which coordinate systems to adopt.

Lattice-based cryptography is one of the most promising schemes for post-quantum cryptography. Among the many lattice-based cryptosystems, FrodoKEM is a well-known key-encapsulation mechanism (KEM) based on (plain) learning with errors (LWE) problems and is advantageous in that the hardness is based on the problem of unstructured lattices. There are many cryptosystems that adopt error-correcting codes (ECCs) to improve performance, such as LAC, ThreeBears, and Round5. However, for lattice-based cryptosystems that do not use ring structures such as FrodoKEM, it is difficult to use ECCs because the number of transmitted symbols is small. In this study, we propose a method to apply ECCs and Gray codes to FrodoKEM by encoding the bits converted from the encrypted symbols. It is shown that the proposed method improves the security level and/or the bandwidth of FrodoKEM, and 192 message bits, 50% more than the original 128 bits, can be transmitted using one of the modified Frodo-640's.

Background: It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. Methods: Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 (“MrgprA3/TRPA1”), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. Results: CQ-induced Ca2+ influx was strongly inhibited by KRGE (10 μg/mL) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca2+ influx in MrgprA3/TRPA1. Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca2+ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)]. Conclusion: The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels. Keywords: ginsenoside Rg3, itch, Korean Red Ginseng, MrgprA3, TRPA1

Abstract Background To evaluate the effects of Huang Bai (Phellodendron amurense) on growth and maturation in adolescent female rats. Methods Female Sprague–Dawley rats (28 days old; n = 72) were divided into six daily treatment groups: control (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20 μg/kg), estradiol (1 μg/kg), and triptorelin (100 μg). Body weight, food intake, and vaginal opening were measured daily from postnatal day (PND) 28 to PND 43. Tetracycline (20 mg/kg) was injected on PND 41. After sacrifice on PND 43, the ovaries and uterus were weighed, and the tibias were fixed in 4% paraformaldehyde. Decalcified and dehydrated tibias were sectioned at a thickness of 40 μm, and sectioned tissues were examined with a fluorescence microscope. Insulin-like growth factor (IGF)-1 and bone morphogenetic protein (BMP)-2 were detected using immunohistochemistry. Results Relative to controls, body weight was higher in the triptorelin group. Bone growth rate increased in the Huang Bai 100 mg/kg (354.00 ± 31.1 μm/day), rhGH (367.10 ± 27.11 μm/day), and triptorelin (374.50 ± 25.37 μm/day) groups. Expression of IGF-1 and BMP-2 in the hypertrophic zone was higher in all experimental groups. Vaginal opening occurred earlier in the estradiol group (PND 33.58 ± 1.62) than in controls and later in the triptorelin group (PND > 43). Ovarian and uterine weights were lower in the oestradiol and triptorelin groups. However, Huang Bai had nonsignificant effects on vaginal opening and the weights of ovaries and the uterus. Conclusions Huang Bai stimulated bone growth by upregulating IGF-1 and BMP-2 in the growth plate. However, it had no effect on pubertal development.

H7 low pathogenic avian influenza viruses (LPAIVs) can mutate into highly pathogenic avian influenza viruses (HPAIVs). In addition to avian species, H7 avian influenza viruses (AIVs) also infect humans. In this study, two AIVs, H7N9 (20X-20) and H7N7 (34X-2), isolated from the feces of wild birds in South Korea in 2021, were genetically analyzed. The HA cleavage site of the two H7 Korean viruses was confirmed to be ELPKGR/GLF, indicating they are LPAIVs. There were no amino acid substitutions at the receptor-binding site of the HA gene of two H7 Korean viruses compared to that of A/Anhui/1/2013 (H7N9), which prefer human receptors. In the phylogenetic tree analysis, the HA gene of the two H7 Korean viruses shared the highest nucleotide similarity with the Korean H7 subtype AIVs. In addition, the HA gene of the two H7 Korean viruses showed high nucleotide similarity to that of the A/Jiangsu/1/2018(H7N4) virus, which is a human influenza virus originating from avian influenza virus. Most internal genes (PB2, PB1, PA, NP, NA, M, and NS) of the two H7 Korean viruses belonged to the Eurasian lineage, except for the M gene of 34X-2. This result suggests that active reassortment occurred among AIVs. In pathogenicity studies of mice, the two H7 Korean viruses replicated in the lungs of mice. In addition, the body weight of mice infected with 34X-2 decreased 7 days post-infection (dpi) and inflammation was observed in the peribronchiolar and perivascular regions of the lungs of mice. These results suggest that mammals can be infected with the two H7 Korean AIVs. Our data showed that even low pathogenic H7 AIVs may infect mammals, including humans, as confirmed by the A/Jiangsu/1/2018(H7N4) virus. Therefore, continuous monitoring and pathogenicity assessment of AIVs, even of LPAIVs, are required.

Astragalus extract mixture HT042 is a standardized functional food granted by the Korean FDA for promoting “Children’s Height Growth”. In this study, we determined whether HT042 affects circulatory Insulin-like growth factor-1 (IGF-1) after administration and investigated whether Growth hormone (GH), Growth hormone-releasing hormone receptor (GHRH-R), and Growth hormone secretagogue receptor (GHS-R) mRNAs are expressed in the pituitary, and whether Growth hormone-releasing hormone (GHRH) and Somatostatin (SST) are expressed in the hypothalamus. We also evaluated the growth effect of HT042 on endochondral bone formation. Male Sprague-Dawley rats in the control and HT042 groups were orally administered a single dose of the control and HT042, respectively, and those in the recombinant human GH (rhGH) group were subcutaneously injected with rhGH. Tetracycline was injected intraperitoneally 72 h prior to sacrifice to decide endochondral bone formation. To determine the endocrine or paracrine/autocrine mechanism, we evaluated the expression of local BMP-2 and IGF-1, an immunohistochemical study after HT042 administration. It was confirmed that the growth-promoting effect of HT042 can be contributed to the increase in serum IGF-1, which can be stimulated by GH secretion. Administration of HT042 modulated the activity of GHRH-R and GHR-S in the pituitary gland and promoted GH secretion, thereby changing longitudinal growth through GH/IGF-1 mediation. Results for GHRH and SST expression demonstrated that the hypothalamus can be influenced and mediated by HT042 through a complex neuroendocrine regulatory system. In addition, it was confirmed by oral administration for 10 days that HT042 increased bone formation in cartilage, which is important for height growth. The effect of HT042 could be owing to upregulation of local Bone morphogenetic protein-2 (BMP-2) and IGF-1 expression in the growth plate, which could be regarded as a GH-dependent autocrine/paracrine pathway, as well as circulatory IGF-1.

Neurological diseases in cattle can be caused by several infectious agents. Astroviruses are increasingly recognized as the causative agent of encephalitis in various animals, including humans. In this study, a neuroinvasive astrovirus (BoAstV 20B05) was discovered in the brain tissues of an 81-month-old Korean native cattle with neurological symptoms. Lymphocyte infiltration and multifocal perivascular cuffing were observed in the cerebrum and brain stem, and viral antigens were also detected in the meninges. In particular, the concentration of the astroviral genome was high in the brain tissues. Korean BoAstV 20B05 was classified into the CH13/NeuroS1 clade and was closely related to the Neuro-Uy and KagoshimaSR28-462 strains. Our evolutionary analysis showed that Korean BoAstV 20B05 belongs to the sub-lineage NeuroS1 and evolved independently of BoAstV KagoshimaSR28-462. These results suggest that neuroinvasive astroviruses were first introduced in Korea. However, analysis is limited by the lack of reference astrovirus sequences reported in various countries within Asia, and further analysis should be performed using more strains. In this study, we identified a neuroinvasive astrovirus infection with neurological symptoms for the first time in South Korea and confirmed that BoAstV 20B05 may have been introduced in South Korea a long time ago.

Objective Adult appendicitis (AA) with equivocal computed tomography (CT) findings remains a diagnostic challenge for physicians. Herein we evaluated the diagnostic performance of several clinical scoring systems in adult patients with suspected appendicitis and equivocal CT findings. Methods We retrospectively evaluated 189 adult patients with equivocal CT findings. Alvarado, Eskelinen, appendicitis inflammatory response, Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA), and adult appendicitis score (AAS) scores were evaluated, receiver operating characteristic analysis was conducted, and the optimal, low, and high cut-off values were determined for patient classification into three groups: low, intermediate, or high. Results In total, 61 patients were included in the appendicitis group and 128 in the non-appendicitis group. There were no significant differences between the area under the curve of the clinical scoring systems in the final diagnosis of AA for equivocal appendicitis on CT (Alvarado, 0.698; Eskelinen, 0.710; appendicitis inflammatory response, 0.668; RIPASA, 0.653; AAS, 0.726). A RIPASA score greater than 7.5 had a high positive predictive value (90.9) and an AAS score less than or equal to 5 had a high negative predictive value (91.7) in the diagnosis of AA. Conclusion The accuracy of clinical scoring systems in the diagnosis of AA with equivocal CT findings was moderate. Therefore, a high RIPASA score may assist in the diagnosis of AA in patients with equivocal CT findings, and a low AAS score may be used as a criterion for patient discharge. Most patients presented with intermediate scores. The patients with equivocal CT findings may be considered as a third diagnostic category of AA.

Purpose The aim of this study was to assess the characteristics of papillary thyroid carcinoma (PTC) in patients aged 65 and older in order to predict postoperative recurrence based on the results of ultrasonographic surveillance. Methods Among 1,494 patients (200 male and 1,294 female; mean age, 46.6±11.3 years) who underwent surgery for thyroid cancer at our institution between 2006 and 2015, we retrospectively enrolled 150 PTC patients (29 male and 121 female; mean age, 69.4±4.2 years). To identify the risk factors for recurrence, we analyzed age, gender, multiplicity, size, number, extrathyroidal extension (ETE) of the tumor, lymph node metastasis (LNM), type of surgery, and the dose of radioactive ablation using a Cox regression model to identify hazard ratios (HRs). Results Among the 115 asymptomatic patients with PTCs detected by screening ultrasonography (n=86), other cross-sectional imaging modalities (computed tomography or positron emission tomography-computed tomography, n=13), or incidentally through a surgical specimen (n=16), 78 patients were confirmed to have papillary thyroid microcarcinomas (PTMCs). The other 35 patients presented with palpable neck masses (n=25), vocal cord palsy (n=9) or blood-tinged sputum (n=1). During the follow-up period (mean, 43.6 months), 17 patients (12.5%) experienced recurrence in the neck. None of the patients died due to PTC-related recurrence or distant metastasis during the follow-up period. Cox regression analysis demonstrated that tumor size (HR, 2.12; P

Abstract The precise clinicopathologic significance of myeloid differentiation primary response gene (MYD88) L265P mutation in diffuse large B-cell lymphomas (DLBCLs) remains elusive. To investigate the frequency and clinicopathologic significance of the MYD88 L265P mutation in DLBCLs, we conducted a meta-analysis of 40 published studies on 2736 DLBCL patients. We collected relevant published research findings identified using the PubMed and Embase databases. The effect sizes of outcome parameters were calculated using a random-effects model. In this meta-analysis, the MYD88 L265P mutation in DLBCL showed a significant difference according to tumor sites. The overall incidence of the MYD88 L265P mutation in DLBCLs, excluding the central nervous system and testicular DLBCLs, was 16.5%. Notably, the MYD88 L265P mutation rates of CNS and testicular DLBCL patients were 60% and 77%, respectively. Interestingly, the MYD88 L265P mutation was more frequently detected in activated B-cell-like (ABC) or non-germinal center B-cell-like (GCB) than GCB subtype (OR = 3.414, p

AIM: To evaluate the effect of exogenous recombinant human bone morphogenic protein-7 (rhBMP-7) on transforming growth factor-β (TGF-β)-induced epithelial mesenchymal cell transition (EMT) and assessed its antifibrotic effect via topical application. METHODS: The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells (HECEs) was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid (HA). EMT markers, fibronectin, E-cadherin, α-smooth muscle actin (α-SMA), and matrix metaloproteinase-9 (MMP-9), were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7. RESULTS: Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion (31.6%; P

This study aimed to examine the association between disability and cardiovascular (CV) disease incidence and mortality in Korea longitudinally, using a national representative sample. We used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, which includes information on the disability of the National Screening Program participants such as severity and type of disability, which were obtained from the Korean National Disability Registry. Cox proportional hazard models were used to evaluate the association between disability and CV disease incidence and mortality. We constructed four models with different levels of adjustment, in which Model 3 was a fully adjusted model. This study included 514,679 participants, and 7,317 CV deaths were reported within a mean follow up of 10.8 ± 3.9 years (maximum, 13.9 years). For 5,572,130 person-year (PY) follow-up, the CV mortality rate was 1.313 per 1,000 PY. In Models 1 and 2, CV disease incidence was significantly higher in participants with disability than in those without disability. In Model 3, the incidence was higher only among participants aged 50-64 years and severe disabled participants aged

In this study, we aimed to investigate the molecular biomarkers that are pivotal for the development and progression of gastric cancer (GC). We analyzed clinical specimens using RNA sequencing to identify the target genes. We found that the expression of HOXC6 mRNA was upregulated with the progression of cancer, which was validated by quantitative real time PCR and RNA in-situ hybridization. To compare the protein expression of HOXC6, we evaluated GC and normal gastric tissue samples using western blot analysis and immunohistochemistry. We detected significantly higher levels of HOXC6 in the GC tissues than in the normal controls at both mRNA and protein levels. The expression levels of HOXC6 mRNA in patients with advanced gastric cancer (AGC) were significantly higher than those in patients with early gastric cancer (EGC). Kaplan-Meier curves showed that high expression of HOXC6 mRNA is significantly associated with poor clinical prognosis. Our findings suggest that HOXC6 mRNA may be a novel biomarker and can be potentially valuable in predicting the prognosis of GC patients. Especially, HOXC6 mRNA in-situ hybridization may be a diagnostic tool for predicting prognosis of individual GC patients.

Wild aquatic birds, a natural reservoir of avian influenza viruses (AIVs), transmit AIVs to poultry farms, causing huge economic losses. Therefore, the prevalence and genetic characteristics of AIVs isolated from wild birds in South Korea from October 2019 to March 2020 were investigated and analyzed. Fresh avian fecal samples (3256) were collected by active monitoring of 11 wild bird habitats. Twenty-eight AIVs were isolated. Seven HA and eight NA subtypes were identified. All AIV hosts were Anseriformes species. The HA cleavage site of 20 representative AIVs was encoded by non-multi-basic amino acid sequences. Phylogenetic analysis of the eight segment genes of the AIVs showed that most genes clustered within the Eurasian lineage. However, the HA gene of H10 viruses and NS gene of four viruses clustered within the American lineage, indicating intercontinental reassortment of AIVs. Representative viruses likely to infect mammals were selected and evaluated for pathogenicity in mice. JB21-58 (H5N3), JB42-93 (H9N2), and JB32-81 (H11N2) were isolated from the lungs, but JB31-69 (H11N9) was not isolated from the lungs until the end of the experiment at 14 dpi. None of infected mice showed clinical sign and histopathological change in the lung. In addition, viral antigens were not detected in lungs of all mice at 14 dpi. These data suggest that LPAIVs derived from wild birds are unlikely to be transmitted to mammals. However, because LPAIVs can reportedly infect mammals, including humans, continuous surveillance and monitoring of AIVs are necessary, despite their low pathogenicity.