Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors.

BACKGROUND: The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. RESULTS: Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. CONCLUSION: A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category.

Parental stress of Korean immigrants in the U.S.: Meeting Child and Youth's educational needs amid the COVID-19 pandemic.

This study investigates Korean immigrants' parental stress amid the COVID-19 pandemic, especially when they experience difficulties trying to meet their children's educational needs. Korean immigrant parents residing in the U.S. were invited to complete an online survey through purposive sampling. The final sample included a total of 341 Korean immigrant parents from 42 U.S. states. Three models of Ordinary Least Squares (OLS) regressions were conducted to examine the associations between parent-reported difficulties meeting the children's educational needs, parental stress, and the immigrant parents' resilience and social support. Findings indicate that parents' difficulties meeting their children's educational needs in general as well as language barriers were associated with increased parental stress. Moreover, parents' resilience and social support also significantly decreased parental stress levels. Implications for practice, policy, and future research are presented.

Anti-Colitic Effects of Ethanol Extract of Persea americana Mill. through Suppression of Pro-Inflammatory Mediators via NF-κB/STAT3 Inactivation in Dextran Sulfate Sodium-Induced Colitis Mice.

Persea americana Mill, cv. Hass, also known as avocado, has been reported to possess hypolipidemic, anti-diabetic, anti-oxidant, cardioprotective, and photoprotective potencies. However, few studies have reported its anti-colitic effects. In this study, we investigated anti-colitic effects of ethanol extract of P. americana (EEP) in dextran sulfate sodium (DSS)-induced colitic mice and the involved molecular mechanisms. EEP effectively improved clinical signs and histological characteristics of DSS-induced colitis mice. In DSS-exposed colonic tissues, EEP reduced expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. Moreover, EEP suppressed DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Consistent with in vivo results, EEP also suppressed protein and mRNA expression levels of iNOS, COX-2, and pro-inflammatory cytokines via NF-κB and STAT3 inactivation in LPS-induced RAW 264.7 macrophages. Taken together, our data indicate that ethanol extract of avocado may be used as a promising therapeutic against inflammatory bowel diseases by suppressing the NF-κB and STAT3 signaling pathway.

ß-Caryophyllene in the Essential Oil from Chrysanthemum Boreale Induces G1 Phase Cell Cycle Arrest in Human Lung Cancer Cells.

Chrysanthemum boreale is a plant widespread in East Asia, used in folk medicine to treat various disorders, such as pneumonia, colitis, stomatitis, and carbuncle. Whether the essential oil from C. boreale (ECB) and its active constituents have anti-proliferative activities in lung cancer is unknown. Therefore, we investigated the cytotoxic effects of ECB in A549 and NCI-H358 human lung cancer cells. Culture of A549 and NCI-H358 cells with ECB induced apoptotic cell death, as revealed by an increase in annexin V staining. ECB treatment reduced mitochondrial membrane potential (MMP), disrupted the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins, and activated caspase-8, -9, and -3, as assessed by western blot analysis. Interestingly, pretreatment with a broad-spectrum caspase inhibitor (z-VAD-fmk) significantly attenuated ECB-induced apoptosis. Furthermore, gas chromatography-mass spectrometry (GC/MS) analysis of ECB identified six compounds. Among them, ß-caryophyllene exhibited a potent anti-proliferative effect, and thus was identified as the major active compound. ß- Caryophyllene induced G1 cell cycle arrest by downregulating cyclin D1, cyclin E, cyclin-dependent protein kinase (CDK) -2, -4, and -6, and RB phosphorylation, and by upregulating p21CIP1/WAF1 and p27KIP1. These results indicate that ß-caryophyllene exerts cytotoxic activity in lung cancer cells through induction of cell cycle arrest.

Novel Rhodanine Derivative, 5-[4-(4-Fluorophenoxy) phenyl]methylene-3-{4-[3-(4-methylpiperazin-1-yl) propoxy]phenyl}-2-thioxo-4-thiazolidinone dihydrochloride, Induces Apoptosis via Mitochondria Dysfunction and Endoplasmic Reticulum Stress in Human Colon Cancer Cells.

We previously reported that 5-[4-(4-fluorophenoxy) phenyl] methylene-3-{4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}-2-thioxo-4-thiazolidinone dihydrochloride (KSK05104) has potent, selective and metabolically stable IKKß inhibitory activities. However, the apoptosis-inducing of KSK05104 and its underlying mechanism have not yet been elucidated in human colon cancer cells. We show that KSK05104 triggered apoptosis, as indicated by externalization of Annexin V-targeted phosphatidylserine residues in HT-29 and HCT-116 cells. KSK05104 induced the activation of caspase-8, -9, and -3, and the cleavage of poly (ADP ribose) polymerase-1 (PARP-1). KSK05104-induced apoptosis was significantly suppressed by pretreatment with z-VAD-fmk (a broad caspase inhibitor). KSK05104 also induced release of cytochrome c (Cyt c), apoptosis inducing factor (AIF), and endonuclease G (Endo G) by damaging mitochondria, resulting in caspase-dependent and -independent apoptotic cell death. KSK05104 triggered endoplasmic reticulum (ER) stress and changed the intracellular calcium level ([Ca2+]i). Interestingly, treatment with KSK05104 activated not only ER stress marker proteins including inositol-requiring enzyme 1-alpha (IRE-1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), but also µ-calpain, and caspase-12 in a time-dependent manner. KSK05104-induced apoptosis substantially decreased in the presence of BAPTA/AM (an intracellular calcium chelator). Taken together, these results suggest that mitochondrial dysfunction and ER stress contribute to KSK05104-induced apoptosis in human colon cancer cells.

Noise in the passenger cars of high-speed trains.

The aim of this study is to investigate the effects of both room acoustic conditions and spectral characteristics of noises on acoustic discomfort in a high-speed train's passenger car. Measurement of interior noises in a high-speed train was performed when the train was operating at speeds of 100 km/h and 300 km/h. Acoustic discomfort caused by interior noises was evaluated by paired comparison methods based on the variation of reverberation time (RT) in a passenger car and the spectral differences in interior noises. The effect of RT on acoustic discomfort was not significant, whereas acoustic discomfort significantly varied depending on spectral differences in noise. Acoustic discomfort increased with increment of the sound pressure level (SPL) ratio at high frequencies, and variation in high-frequency noise components were described using sharpness. Just noticeable differences of SPL with low- and high-frequency components were determined to be 3.7 and 2.9 dB, respectively. This indicates that subjects were more sensitive to differences in SPLs at the high-frequency range than differences at the low-frequency range. These results support that, for interior noises, reduction in SPLs at high frequencies would significantly contribute to improved acoustic quality in passenger cars of high-speed trains.

Speech privacy and annoyance considerations in the acoustic environment of passenger cars of high-speed trains.

It is necessary to consider not only annoyance of interior noises but also speech privacy to achieve acoustic comfort in a passenger car of a high-speed train because speech from other passengers can be annoying. This study aimed to explore an optimal acoustic environment to satisfy speech privacy and reduce annoyance in a passenger car. Two experiments were conducted using speech sources and compartment noise of a high speed train with varying speech-to-noise ratios (SNRA) and background noise levels (BNL). Speech intelligibility was tested in experiment I, and in experiment II, perceived speech privacy, annoyance, and acoustic comfort of combined sounds with speech and background noise were assessed. The results show that speech privacy and annoyance were significantly influenced by the SNRA. In particular, the acoustic comfort was evaluated as acceptable when the SNRA was less than -6 dB for both speech privacy and noise annoyance. In addition, annoyance increased significantly as the BNL exceeded 63 dBA, whereas the effect of the background-noise level on the speech privacy was not significant. These findings suggest that an optimal level of interior noise in a passenger car might exist between 59 and 63 dBA, taking normal speech levels into account.

Soundscape evaluation in a Catholic cathedral and Buddhist temple precincts through social surveys and soundwalks.

Religious precincts in urban spaces have their own religious spatiality formed by their sociocultural and historical background. It is necessary to identify the spatiality of urban religious precincts in their sociocultural contexts because soundscape perception is determined largely by context. In the present study, social surveys and soundwalks were performed in a Catholic cathedral and in Buddhist temple precincts in Seoul. In the surveys, important spatial functions, sound, and visual components of the Catholic cathedral and Buddhist temple precincts were investigated by principal component analysis. The results showed that the cathedral precincts play a more important role in social functions related to mainly visual components than the temple precincts do, whereas the functions for religious activities related to sound elements are more stressed in the temple precincts. In the soundwalk evaluation, contributions of soundscape and landscape components to tranquility in the two religious precincts were explored. It was found that pleasantness of soundscape and attractiveness of landscape significantly affected the perception of tranquility. In addition, it was revealed that a sense of enclosure could enhance tranquility in urban religious precincts.

Designing sound and visual components for enhancement of urban soundscapes.

The aim of this study is to investigate the effect of audio-visual components on environmental quality to improve soundscape. Natural sounds with road traffic noise and visual components in urban streets were evaluated through laboratory experiments. Waterfall and stream water sounds, as well as bird sounds, were selected to enhance the soundscape. Sixteen photomontages of a streetscape were constructed in combination with two types of water features and three types of vegetation which were chosen as positive visual components. The experiments consisted of audio-only, visual-only, and audio-visual conditions. The preferences and environmental qualities of the stimuli were evaluated by a numerical scale and 12 pairs of adjectives, respectively. The results showed that bird sounds were the most preferred among the natural sounds, while the sound of falling water was found to degrade the soundscape quality when the road traffic noise level was high. The visual effects of vegetation on aesthetic preference were significant, but those of water features relatively small. It was revealed that the perceptual dimensions of the environment were different from the noise levels. Particularly, the acoustic comfort factor related to soundscape quality considerably influenced preference for the overall environment at a higher level of road traffic noise.

Soundwalk approach to identify urban soundscapes individually.

This study proposes a soundwalk procedure for evaluating urban soundscapes. Previous studies, which adopted soundwalk methodologies for investigating participants' responses to visual and acoustic environments, were analyzed considering type, evaluation position, measurement, and subjective assessment. An individual soundwalk procedure was then developed based on asking individual subjects to walk and select evaluation positions where they perceived any positive or negative characteristics of the urban soundscape. A case study was performed in urban spaces and the results were compared with those of the group soundwalk to validate the individual soundwalk procedure. Thirty subjects (15 architects and 15 acousticians) participated in the soundwalk. During the soundwalk, the subjects selected a total of 196 positions, and those were classified into 4 groups. It was found that soundscape perceptions were dominated by acoustic comfort, visual images, and openness. It was also revealed that perceived elements of the acoustic environment and visual image differed across classified soundscape groups, and there was a difference between architects and acousticians in terms of how they described their impressions of the soundscape elements. The results show that the individual soundwalk procedure has advantages for measuring diverse subjective responses and for obtaining the perceived elements of the urban soundscape.

Glucose Control in Korean Patients with Type 2 Diabetes Mellitus according to Body Mass Index.

Background: The prevalence of type 2 diabetes mellitus has continued to rise. Although many studies have focused on the connection between weight loss and glucose control, only a few studies have investigated the association between body mass index (BMI) and glucose control status. We examined the association between glucose control and obesity. Methods: We analyzed 3,042 participants with diabetes mellitus who were aged ≥19 years when they participated in the 2014 to 2018 Korean National Health and Nutrition Examination Survey. The participants were divided into four groups according to their BMI (<18.5, 18.5-23, 23-25, and ≥25 kg/m2). We used guidelines from the Korean Diabetes Association to compare the glucose control in those groups, with a cross-sectional design, multivariable logistic regression, and glycosylated hemoglobin <6.5% as the reference. Results: Overweight males aged ≥60 years had a high odds ratio (OR) for degraded glucose control (OR, 1.706; 95% confidence interval [CI], 1.151 to 2.527). Among obese females, those in the ≥60 years age group showed an increased OR for uncontrolled diabetes (OR, 1.516; 95% CI, 1.025 to 1.892). Moreover, in females, the OR for uncontrolled diabetes tended to increase as the BMI increased (P=0.017). Conclusion: Obesity is associated with uncontrolled diabetes in female patients with diabetes who are aged ≥60 years. Physicians should closely monitor this group for diabetes control.

Racial Discrimination as a Cumulative Risk Factor Affecting Parental Stress on the Psychological Distress of Korean Americans (Both US- and Foreign-Born) amid COVID-19: Structural Equation Modeling.

This study examined the relationships of parental stress and racial discrimination to the psychological distress of Korean Americans (both US- and foreign-born) during the COVID-19 pandemic. It also explored whether racial discrimination moderated the effect of parental stress on psychological distress. Using primary data collected between May 24, 2020, and June 14, 2020, via an online questionnaire, confirmatory factor analysis and structural equation models were conducted on 339 Korean American parents. Results indicated that parental stress and racial discrimination were associated with parental psychological distress. However, when the sample was divided by parental sex, racial discrimination played as a moderator, the interaction of discrimination, and parenting stress was associated with more psychological distress only for mothers. Based on the study results, we recommended that policymakers should consider policies and programs that can reduce racism to make up for the public health crisis associated with COVID-19; clinical practitioners also need to provide appropriate virtual mental/physical health services and interventions that can decrease parental stress and psychological distress amid COVID-19.

Non-auditory factors affecting urban soundscape evaluation.

The aim of this study is to characterize urban spaces, which combine landscape, acoustics, and lighting, and to investigate people's perceptions of urban soundscapes through quantitative and qualitative analyses. A general questionnaire survey and soundwalk were performed to investigate soundscape perception in urban spaces. Non-auditory factors (visual image, day lighting, and olfactory perceptions), as well as acoustic comfort, were selected as the main contexts that affect soundscape perception, and context preferences and overall impressions were evaluated using an 11-point numerical scale. For qualitative analysis, a semantic differential test was performed in the form of a social survey, and subjects were also asked to describe their impressions during a soundwalk. The results showed that urban soundscapes can be characterized by soundmarks, and soundscape perceptions are dominated by acoustic comfort, visual images, and day lighting, whereas reverberance in urban spaces does not yield consistent preference judgments. It is posited that the subjective evaluation of reverberance can be replaced by physical measurements. The categories extracted from the qualitative analysis revealed that spatial impressions such as openness and density emerged as some of the contexts of soundscape perception.

PG-path: Modeling and personalizing pharmacogenomics-based pathways.

A pharmacogenomics-based pathway represents a series of reactions that occur between drugs and genes in the human body after drug administration. PG-path is a pharmacogenomics-based pathway that standardizes and visualizes the components (nodes) and actions (edges) involved in pharmacokinetic and pharmacodynamic processes. It provides an intuitive understanding of the drug response in the human body. A pharmacokinetic pathway visualizes the absorption, distribution, metabolism, and excretion (ADME) at the systemic level, and a pharmacodynamic pathway shows the action of the drug in the target cell at the cellular-molecular level. The genes in the pathway are displayed in locations similar to those inside the body. PG-path allows personalized pathways to be created by annotating each gene with the overall impact degree of deleterious variants in the gene. These personalized pathways play a role in assisting tailored individual prescriptions by predicting changes in the drug concentration in the plasma. PG-path also supports counseling for personalized drug therapy by providing visualization and documentation.

Predicting Psychological Distress Amid the COVID-19 Pandemic by Machine Learning: Discrimination and Coping Mechanisms of Korean Immigrants in the U.S.

The current study examined the predictive ability of discrimination-related variables, coping mechanisms, and sociodemographic factors on the psychological distress level of Korean immigrants in the U.S. amid the COVID-19 pandemic. Korean immigrants (both foreign-born and U.S.-born) in the U.S. above the age of 18 were invited to participate in an online survey through purposive sampling. In order to verify the variables predicting the level of psychological distress on the final sample from 42 states (n = 790), the Artificial Neural Network (ANN) analysis, which is able to examine complex non-linear interactions among variables, was conducted. The most critical predicting variables in the neural network were a person's resilience, experiences of everyday discrimination, and perception that racial discrimination toward Asians has increased in the U.S. since the beginning of the COVID-19 pandemic.

Effects of adding natural sounds to urban noises on the perceived loudness of noise and soundscape quality.

Introducing pleasant natural sounds to mask urban noises is an important soundscape design strategy to improve acoustic comfort. This study investigates the effects of signal-to-noise ratio (SNR) between natural sounds (signal) and the target noises (noise) and their temporal characteristics on the perceived loudness of noise (PLN) and overall soundscape quality (OSQ) through a laboratory experiment. Two types of urban noise sources (hydraulic breaker and traffic noises) were set to A-weighted equivalent sound pressure levels (SPL) of 55, 65, and 75 dB and then augmented with two types of natural sounds (birdsong and stream), across a range of SNRs. Each acoustic stimulus was a combination of noise and natural sound at SNRs from -6 to 6 dB. Averaged across all cases, the subjective assessment of PLN showed that augmenting urban noise separately with the two natural sounds reduced the PLN by 17.9%, with no significant differences found between the birdsong and stream sounds. Adding natural sounds increased the OSQ by on average 18.3% across the cases, but their effects gradually decreased as the noise level increased. The OSQ of the birdsong and stream sounds were similar for traffic noise, whereas the stream sound was rated higher than the birdsong for the breaker noise. The results suggest that increasing the dissimilarity in temporal structure between the target noise and natural sounds could enhance the soundscape quality. Appropriate SNRs were explored considering both PLN and OSQ. The results showed that the SNR of -6 dB was desirable when the A-weighted SPL of the noise rose to 75 dB.

The effect of two locally administered anti-resorptive agents on bone regeneration in a rat fibula model: Alendronate and 15-deoxy-Δ12,14-prostaglandin J2.

Bisphosphonates are well-known drugs as inhibitors of bone resorption acting on inducing programmed cell death of osteoclasts. However, many in vitro studies report that optimal concentration of the bisphosphonate affects not only osteoclasts but also osteoblasts, that is, it induces the anabolic effects of osteoblasts. Recently reported 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an endogenous ligand of peroxisome proliferator-activated receptor-gamma, with an inhibitory activity on bone loss. Researchers have also suggested that 15d-PGJ2 has the ability to reduce bone destruction and as the possibility of regeneration of bone. The purpose of this study is to demonstrate the anabolic effect of two anti-resorptive materials, alendronate and 15d-PGJ2, in a critical sized segmental defect model of rat fibula. The regenerated bone on the operative site was assessed through gross, radiographic (plain X-ray, and micro-computed tomography), histomorphologic evaluation, and statistical analysis. Consequently, the locally applied alendronate prevented resorption of grafted materials, and had a positive effect on bone regeneration with positive micro-architectural modification of the surrounding bone, although this study did not verify a significant capacity of bone regeneration of 15d-PGJ2 and instead only shed a light on its possibility.

The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation.

We previously reported the potential anti-proliferative activity of 3-(5,6,7-trimethoxy-4-oxo-4H-chromen-2-yl)-N-(3,4,5-trimethoxyphenyl) benzamide (TMS-TMF-4f) against human cancer cells; however, the underlying molecular mechanisms have not been investigated. In the present study, TMS-TMF-4f showed the highest cytotoxicity in human cervical cancer cells (HeLa and CaSki) and low cytotoxicity in normal ovarian epithelial cells. Annexin V-FITC and propidium iodide (PI) double staining revealed that TMS-TMF-4f-induced cytotoxicity was caused by the induction of apoptosis in both HeLa and CaSki cervical cancer cells. The compound TMS-TMF-4f enhanced the activation of caspase-3, caspase-8, and caspase-9 and regulated Bcl-2 family proteins, which led to mitochondrial membrane potential (MMP) loss and resulted in the release of cytochrome c and Smac/DIABLO into the cytosol. Also, TMS-TMF-4f suppressed both constitutive and IL-6-inducible levels of phosphorylated STAT3 (p-STAT3) and associated proteins such as Mcl-1, cyclin D1, survivin, and c-Myc in both cervical cancer cells. STAT-3 overexpression completely ameliorated TMS-TMF-4f-induced apoptotic cell death and PARP cleavage. Docking analysis revealed that TMS-TMF-4f could bind to unphosphorylated STAT3 and inhibit its interconversion to the activated form. Notably, intraperitoneal administration of TMS-TMF-4f (5, 10, or 20 mg/kg) decreased tumor growth in a xenograft cervical cancer mouse model, demonstrated by the increase in TUNEL staining and PARP cleavage and the reduction in p-STAT3, Mcl-1, cyclin D1, survivin, and c-Myc expression levels in tumor tissues. Taken together, our results suggest that TMS-TMF-4f may potentially inhibit human cervical tumor growth through the induction of apoptosis via STAT3 suppression.

Natural products hybrids: 3,5,4'-Trimethoxystilbene-5,6,7-trimethoxyflavone chimeric analogs as potential cytotoxic agents against diverse human cancer cells.

Cancer still represents a major global health problem. All currently available anticancer agents have disadvantages like resistance or side effects. Therefore, introduction of novel anticancer agents is needed. Intrigued by the high success rate for natural products-based drug discovery, we designed and synthesized antiproliferative chemical entities as hybrids of two natural products; 3,5,4'-trimethoxystilbene and 5,6,7-trimethoxyflavone. To probe the spectrum of the synthesized compounds, in vitro evaluation was conducted against nine panels representing major cancer diseases. The results revealed the hybrid analogs 4f, 4h, 4k and 4q as promising broad-spectrum anticancer lead compounds eliciting high growth inhibition of several cell lines representing multiple cancers diseases. Evaluation of the promising lead compounds against normal human cell lines suggested a selective cytotoxic effect on cancer cells. Mechanistic investigation of the cytotoxic activity of compound 4f in human cervical cancer HeLa cells showed that it triggers cell death through induction of apoptosis. As a whole, this study presents the natural products hybrid analogs 4f, 4h, 4k and 4q as potential lead compounds for further development of novel anticancer therapeutics.

Pilot Algorithm Designed to Help Early Detection of HMG-CoA Reductase Inhibitor-Induced Hepatotoxicity.

OBJECTIVES: To enable early detection of adverse drug reactions (ADRs) in patients using HMG-CoA reductase inhibitors (statins), we developed an algorithm that automatically detects liver injury caused by statins from Electronic Medical Record (EMR) data. We verified the performance of our algorithm through manual ADR assessment and a direct chart review. METHODS: The subjects in this study were patients who had been prescribed a statin for the first time among outpatients in Seoul St. Mary's Hospital in Korea between January 2009 and December 2012. We extracted basic information about the patients, including laboratory information, underlying disease, diagnosis information, prescription information, and concomitant drugs. We developed an automatic ADR detection algorithm by using EMR data. We validated the results of the algorithm through a chart review. RESULTS: We developed the algorithm to assess ADR occurrences based on alanine transaminase (ALT) and alkaline phosphatase (ALP) levels. According to the proposed algorithm, any of these result options could be attained: ADR-free, little association, strong association, and weak association or indeterminable. The results of the ADR assessments obtained using the proposed algorithm showed that the data of 126 patients (1.4% of all 9,241 patients) included suspicious figures, thus indicating the possibility of an ADR. In the EMR chart review for verifying the algorithm, ADRs of 33 patients were not associated with statin use; therefore, the ADR occurrence rate was found to be 1.0% (93/9,241). Therefore, the positive predictive value was calculated to be 73.8% (93/126; 95% confidence interval, 69.2%-77.6%). No differences were observed between statin types (p = 0.472). CONCLUSIONS: For early detection of statin-induced liver injury, we developed an automatic ADR assessment algorithm. We expect that algorithms that are more reliable can be developed if we conduct supplement clinical studies with a focus on adverse drug effects.