Trends in Saliva Research and Biomedical Clinical Applications / 대한소아치과학회지

Function of salivary gland and saliva composition can be an indicator of individual’s health status. Recently, saliva has been thought to have a high potential for usage in the biomedical field to diagnose, evaluate, and prevent systemic health due to the technological advances in analyzing and detecting small elements such as immunological and metabolic products, viruses, microorganisms, hormones in saliva. As a diagnostic specimen, saliva has some useful advantages compared to serum. Because of simple non-invasive method, saliva sampling is quite comfort for the patient, and it doesn’t require specialists to collect samples. The possibility of infection during the collection process is also low. For this reason, proteins, genetic materials, and various biomarkers in saliva are actively being utilized on studying stress, microbiomics, genetics, and epigenetics. For the research on collecting big data related to systemic health, the needs on biobank has been focused. Regeneration of salivary gland based on tissue engineering has been also on advancement. However, there are still many issues to be solved, such as the standardization of sample collection, storage, and usage. This review focuses on the recent trends in the field of saliva research and highlight the future perspectives in biomedical and other applications.

Utilization of an Artificial Intelligence Program Using the Greulich-Pyle Method to Evaluate Bone Age in the Skeletal Maturation Stage / 대한소아치과학회지

The purpose of this study was to measure bone age using an artificial intelligence program based on the Greulich-Pyle (GP) method to find out the bone age corresponding to each stage of cervical vertebral maturation (CVM) and the middle phalanx of the third finger (MP3). This study was conducted on 3,118 patients who visited pediatric dentistry at Kyung Hee University Dental Hospital and Pusan National University Dental Hospital from 2013 to 2021. The CVM stage was divided into 5 stages according to the classification by Baccetti, and the MP3 stage was divided into 5 stages according to the methods of Hägg and Taranger. Based on the GP method, bone age was evaluated using an artificial intelligence program. The pubertal growth spurt in the CVM stage was CVM II and III. The mean bone age in CVM II was 11.00 ± 1.81 years for males and 10.00 ± 1.49 years for females, and in CVM III, 13.00 ± 1.46 years for males and 12.00 ± 1.44 years for females (p < 0.0001). The pubertal growth spurt in the MP3 stage was MP3 - G stage. The bone age at the MP3 - G stage was 13.14 ± 1.07 years for males and 11.40 ± 1.09 years for females (p < 0.0001). Bone age evaluation using artificial intelligence is worth using in clinical practice, and it is expected that a faster and more accurate diagnosis will be possible.

Life stress, dietary attitudes, and frequency of snack intake for college students in Seoul and Gyeonggi area: the difference between male and female students

BACKGROUND/OBJECTIVES@#This study examines life stress, dietary attitudes, and snacking frequency for college students living in Seoul and Gyeonggi Province. The purpose of this study is to assist college students feeling stressed by offering desirable dietary attitudes and choices of the appropriate snacks by providing educational materials that offer appropriate nutrition education and nutritional information. @*SUBJECTS/METHODS@#A survey was conducted on a total of 600 college students aged 19–29-year-olds living in Seoul and Gyeonggi Province (234 male students and 366 female students). Collected data were analyzed using SPSS WIN 28.0 program. @*RESULTS@#Life stress among college students did not differ significantly between the genders. Male students were more stressed about lover (P < 0.01), while female students were more stressed about value problems (P < 0.01) and future problems (P < 0.05). Dietary attitude ratings were 3.1 for both male and female students with no significant difference. The overall snacking frequency was 4.1 times/day—4.2 times/day for male students and 4.0 times/day for female students—thus, there was no significant difference. Male students consumed ‘beverage’ (P < 0.01) more frequently than female students. Life stress and snacking were positively correlated for ‘biscuit/cookie,’ ‘chip,’ ‘cereal,’ ‘juice/smoothie,’ ‘café americano,’ ‘café latte,’ ‘tea,’ ‘jelly,’ ‘chocolate,’ ‘rice cake,’ ‘milk,’ ‘flavored milk,’ and ‘ice cream’ among male students. Among female students, life stress and snacking were positively correlated with ‘cereal,’ ‘caramel,’ and ‘soymilk,’ and negatively correlated for ‘biscuit/cookie’ and ‘carbonated drink.’ @*CONCLUSIONS@#College students should manage their stress by identifying its causes and learning how to deal with stressful situations. Additionally, providing them with proper nutrition education based on the correct nutritional information is essential for promoting good food attitudes and snacking behaviors.

Dietary supplementation with Korean pine nut oil decreases body fat accumulation and dysregulation of the appetite-suppressing pathway in the hypothalamus of high-fat diet-induced obese mice

BACKGROUND/OBJECTIVES@#Korean pine nut oil (PNO) has been reported to suppress appetite by increasing satiety hormone release. However, previous studies have rendered inconsistent results and there is lack of information on whether dietary Korean PNO affects the expression of satiety hormone receptors and hypothalamic neuropeptides. Therefore, our study sought to evaluate the chronic effects of Korean PNO on the long-term regulation of energy balance.MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed with control diets containing 10% kcal fat from Korean PNO or soybean oil (SBO) (PC or SC) or high-fat diets (HFDs) containing 35% kcal fat from lard and 10% kcal fat from Korean PNO or SBO (PHFD or SHFD) for 12 weeks. The expression of gastrointestinal satiety hormone receptors, hypothalamic neuropeptides, and genes related to intestinal lipid absorption and adipose lipid metabolism was then measured. @*RESULTS@#There was no difference in the daily food intake between PNO- and SBO-fed mice; however, the PC and PHFD groups accumulated 30% and 18% less fat compared to SC and SHFD, respectively. Korean PNO-fed mice exhibited higher messenger RNA (mRNA) expression of Ghsr (ghrelin receptor) and ,Agrp (agouti-related peptide) (P < 0.05), which are expressed when energy consumption is low to induce appetite as well as the appetitesuppressing neuropeptides Pomc and Cartpt (P = 0.079 and 0.056, respectively). Korean PNO downregulated jejunal Cd36 and epididymal Lpl mRNA expressions, which could suppress intestinal fatty acid absorption and fat storage in white adipose tissue. Consistent with these findings, Korean PNO-fed mice had higher levels of fecal non-esterified fatty acid excretion. Korean PNO also tended to downregulate jejunal Apoa4 and upregulate epididymal Adrb3 mRNA levels, suggesting that PNO may decrease chylomicron synthesis and induce lipolysis. @*CONCLUSIONS@#In summary, Korean PNO attenuated body fat accumulation, and appeared to prevent HFD-induced dysregulation of the hypothalamic appetite-suppressing pathway.

Review of Inhalation Health Risks Involving Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) Used as Disinfectants in Household Humidifiers

The association between lung injury and exposure to humidifier disinfectant (HD) containing a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) has been controversial in South Korea. This study conducts a literature review in order to evaluate the likelihood of CMIT/MIT reaching the lower part of the respiratory tract and causing lung injury. A literature review focused on the inhalation risk of HD containing a mixture of CMIT and MIT. The major contents included the physicochemical properties of CMIT and MIT contained in HDs and methodological reviews on substance analysis, toxicity tests and clinical cases. HD products marketed in South Korea have been reported to contain approximately 1–2% CMIT and 0.2–0.6% MIT along with magnesium nitrate (20–25%), magnesium chloride (0.2–1.0%), and water (70–75%). The types of CMIT and MIT dispersed into the air and deposited in the respiratory tract are assumed to be either gaseous substances or nanoparticles mixed with magnesium salts. The result of the literature review including clinical cases of lung injury among CMIT/MIT HD product users, demonstrated that these chemicals likely reach the lower respiratory tract and accordingly cause lung injury.A number of humidifier disinfectant-associated lung injury cases with clinical evidence should be prioritized in risk assessment of HD containing CMIT and MIT, even though there might be insufficient evidence in all related areas, including inhalation exposure assessment studies, animal testing, and epidemiological studies.

Preoperative Factors of Immature First Permanent Molars Treated with Vital Pulp Therapy / 대한소아치과학회지

This study aimed to analyze the preoperative factors of immature first molars treated with vital pulp therapy and to find out their correlation in pediatric patients. From May 2014 to January 2020, 523 patients and 1,242 immature first molars were investigated. Factors including age, sex, tooth location, Molar-incisor hypomineralization (MIH), caries cavity location, and history of previous restoration were evaluated. As a result of the study, the vital pulp therapy group had 5.56 times more MIH, 3.39 times more mesial cavities, and 8.73 times more distal cavities. In order to avoid vital pulp therapy in immature first molar, early diagnosis and active management of MIH and preventive treatment of mesial and distal caries are necessary after its immediate eruption.

Survival Rates of Class II Restoration in Primary Molar with Flowable Resin Composite / 대한소아치과학회지

The purpose of this retrospective study was to evaluate the survival rate by comparing Class II restoration using flowable resin composite with stainless steel crown in primary molars.Electronic medical records and radiographs of 1,504 primary molars with proximal caries of 590 patients from June 2015 to August 2019 were analyzed. With the collected data, survival analysis was performed using the Kaplan-Meier method.The 1-year survival rate of flowable resin composite in the primary molar was 98.5%, 3-year survival rate was 87.7%, and mean survival time was 39 months. There was no statistically significant difference between flowable resin composite and stainless steel crown (p = 0.896).Within the limits of this study, Class II restoration using flowable resin composite can be considered a promising option for the treatment of proximal caries in primary molars.

Effect of Korean pine nut oil on hepatic iron, copper, and zinc status and expression of genes and proteins related to iron absorption in dietinduced obese mice / 한국영양학회지

Purpose@#Body adiposity is negatively correlated with hepatic iron status, and Korean pine nut oil (PNO) has been reported to reduce adiposity. Therefore, we aimed to study the effects of PNO on adiposity, hepatic mineral status, and the expression of genes and proteins involved in iron absorption. @*Methods@#Five-week-old male C57BL/6 mice were fed a control diet containing 10% kcal from PNO (PC) or soybean oil (SBO; SC), or a high-fat diet (HFD) containing 35% kcal from lard and 10% kcal from PNO (PHFD) or SBO (SHFD). Hepatic iron, copper, and zinc content; and expression of genes and proteins related to iron absorption were measured. @*Results@#HFD-fed mice had a higher white fat mass (2-fold; p < 0.001), lower hepatic iron content (25% lower; p < 0.001), and lower hepatic Hamp (p = 0.028) and duodenal Dcytb mRNA levels (p = 0.037) compared to the control diet-fed mice. Hepatic iron status was negatively correlated with body weight (r = −0.607, p < 0.001) and white fat mass (r = −0.745, p < 0.001). Although the PHFD group gained less body weight (18% less; p < 0.05) and white fat mass (18% less; p < 0.05) than the SHFD group, the hepatic iron status impaired by the HFD feeding did not improve. The expression of hepatic and duodenal ferroportin protein was not affected by the fat amount or the oil type. PNO-fed mice had significantly lower Slc11a2 (p = 0.022) and Slc40a1 expression (p = 0.027) compared to SBO-fed mice. However, the PC group had a higher Heph expression than the SC group (p < 0.05). The hepatic copper and zinc content did not differ between the four diet groups, but hepatic copper content adjusted by body weight was significantly lower in the HFD-fed mice compared to the control diet-fed mice. @*Conclusion@#HFD-induced obesity decreased hepatic iron storage by affecting the regulation of genes related to iron absorption; however, the 18% less white fat mass in the PHFD group was not enough to improve the iron status compared to the SHFD group. The hepatic copper and zinc status was not altered by the fat amount or the oil type.

Comparison of Long Term Follow-up Chest CT Imaging in Adult and Pediatric Patients with Humidifier Disinfectant-related Lung Injury

Background@#To compare the chest computed tomography (CT) images of children and adults in families with clusters of humidifier disinfectant-related lung injury (HDLI) after cessation of exposure to humidifier disinfectant (HD). @*Methods@#We reviewed medical records of 19 families with 43 patients (21 adults, 22 children) among families, which had at least one adult and one child with HDLI. Each family was exposed to the same HD exposure environment. @*Results@#In adults, centrilobular nodules were predominant (95.2%) in chronic HDLI findings after cessation of exposure to HD, however, in children, normal pattern was most prevalent on chest CT (45.5%), followed by centrilobular nodule (36.4%), bizarre lung cysts (36.4%), and reticulation (13.6%). @*Conclusion@#Unlike the known chronic HDLI finding of adults, centrilobular nodules were only present in 36.4% of children. The frequency of bizarre lung cysts were significantly greater in children than that in adults after cessation of similar exposure to HD. Thus, bizarre lung cysts may be useful as another novel finding of chronic HDLI in children who have no history of pulmonary infection or other perinatal disorder such as hyaline membrane disease or other interstitial lung disease.

Microleakage Assessment of Resin Infiltration Combined Restoration in Artificial Decalcified-Cavitated Lesion / 대한소아치과학회지

This study was performed to evaluate the restoration combined with resin infiltration (RI) of early cavitated smooth surface caries lesion in terms of microleakage. Flowable resin and resin-modified glass ionomer cement (RMGIC) were compared. Sound 20 extracted 3rd molars were divided into 2 groups randomly. Artificial decalcified lesion was induced. Cavities were prepared on the mesial and distal surfaces, and randomly set as experimental and control group. RI was applied to the experimental group before cavity restoration. The control group was restored without RI. In group I and II, flowable resin and RMGIC was used for restoration respectively. After thermocycling and silver nitrate immersion, microleakage was assessed by μ-CT. Depth of microleakage was lower in experimental group than control group only in group II (p = 0.05). Microleakage depth was lower in group II than group I in both xperimental and control groups (p = 0.05). RI pretreatment before restoration of early cavitated caries lesions might reduce the microleakage and help long-term maintenance of restoration. In this study, RMGIC was less polymerization shrinkage. Restoration with RMGIC after RI pretreatment reduced the microleakage of the restoration compared to the flowable resin.

Serum concentrations of α2-macroglobulin, α1-antitrypsin, and C-reactive protein in dogs with suspected acute pancreatitis / 대한수의학회지

In canine acute pancreatitis (AP), inappropriate release and activation of zymogen proteases within the pancreas results in the consumption of serum antiproteases. The aim of this study was to examine whether the serum concentrations of α₂-macroglobulin (A2MG), α₁-antitrypsin (A1AT), and C-reactive protein (CRP) differ between dogs with AP and healthy dogs. Twenty healthy dogs and 20 dogs with AP were included in this study. Concentrations of A2MG, A1AT, and CRP were measured in the sera of healthy dogs and dogs diagnosed with AP. Serum A2MG and A1AT concentrations were significantly lower in dogs with AP than in healthy dogs, whereas the serum CRP concentration was significantly higher. In addition, the concentrations of A2MG and A1AT were significantly higher in AP survivors than in AP non-survivors, while the CRP concentration was significantly lower. However, in both AP survivors and non-survivors, the CRP concentrations showed a negative correlation with A2MG concentrations but not with A1AT. These findings indicate that serum antiproteases and CRP concentrations might be associated with the mortality rate of AP in dogs.

Utilization of Resin Infiltration for the Minimally Invasive Composite Restoration / 대한소아치과학회지

This study was aimed to assess the new trial for minimal cavity preparation in composite restoration combined with resin infiltration, focusing at application sequence.32 human primary molars with early carious lesions around small cavity were selected and randomly divided into two groups, according to the sequence of cavity preparation (P), composite filling (F) and resin infiltration (I) as IPF and PFI group. Each group was assessed about amount of tooth reduction, features of resin infiltration, and marginal leakage around restoration.Amount of tooth reduction evaluated using micro-CT was decreased compared with the original lesion size in both groups. Features of resin infiltration were verified under confocal laser scanning microscopy. In both groups, infiltrant resin was found on all around the composite and maintained in spite of extent of decalcification even after artificial caries induction. Marginal micro leakage assessed with silver nitrate immersion and micro-CT was found more frequently in PFI group.The technique combining resin infiltration and composite restoration might ensure better adhesion prognosis as applied by the sequence of resin infiltration, cavity preparation, and composite filling. This new trial was thought meaningful in minimizing the cavity size and contributing to minimal invasive dentistry.

Diagnostic Utilization of Laser Fluorescence for Resin Infiltration in Primary Teeth / 대한소아치과학회지

This study was performed to evaluate clinical use of laser fluorescence (LF) to identify early childhood caries lesions suitable for applying resin infiltration.20 exfoliated primary molars with proximal caries were selected and cut buccolingually cross the central pit for regarding the mesial and distal surfaces respectively. 27 specimens corresponding to ICDAS code 1 and 2 were selected and the LF values were measured. When infiltrant resin was applied, double staining for microscopy detection has done simultaneously. Tooth samples were sliced with 0.7 mm thick. The maximum lesion depth, maximum penetration depth, and average penetration rate were measured from the confocal scanning laser microscope image. Pearson correlation analysis was performed.The intraclass correlation coefficient of LF values shows excellent agreement. LF values had positive correlation with penetration rate, but not lesion depth and penetration depth. Significant correlation between LF readings and penetration rate was verified in deep enamel caries and dentin caries except shallow enamel caries.Infiltrant resin could penetrate with a higher rate and LF values could be increased in more active caries lesions. In assessing radiologically similar caries lesion, laser fluorescence might be useful for identifying caries activity.

Effect of Developmental Disorders of Maxillary First Molars on Orofacial Morphology / 대한소아치과학회지

This study was aimed to evaluate orofacial morphologies on the cases of developmental disorders of maxillary first molars.Panoramic radiographs, lateral cephalographs, and clinical photos of 2983 children who attended the Pediatric Dental Clinic of Pusan National University Dental Hospital from 2006 to August 2017 were assessed retrospectively. 34 patients were selected whose maxillary first molars were missed or developmentally delayed unilaterally or bilaterally. Demirjian' s method was used for estimating dental age, then which was compared to chronologic age of children. Parameters expressing skeletal and dentoalveolar disharmony were checked and compared with control. Additionally, occlusion relationship was evaluated.Maxillary dental age was significantly delayed compared to chronologic age. Several parameters which show skeletal open-bite tendency and skeletal class III malocclusion with maxillary retrusion were statistically significant. Anterior crossbite and edge-bite were expected in most of these cases, but compensation by occlusion and soft tissue was also verified which might mask skeletal class III tendency.Congenital missed or developmentally delayed maxillary first molars might be related with declined growth of maxilla. If developmental disorders of maxillary first molars were verified during clinical examination, careful monitoring of orofacial growth was necessary during puberty and timed orthopedic and orthodontic intervention were considered.

Recurrent Optic Neuritis and Acute Encephalopathy with Myelin Oligodendrocyte Glycoprotein Antibodies in a Korean Child

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases are reported to have distinct pathogenic mechanisms, clinical courses, and therapeutic implications in comparison to other acquired demyelinating syndromes. Here, we report the case of a 6-year-old Korean girl with recurrent steroid-responsive optic neuritis (ON) and an episode of acute disseminated encephalomyelitis (ADEM) with a high MOG antibody titer. Initially, she suffered from left ON with subclinical brain lesions including magnetic resonance imaging hyperintensities in the bilateral frontal subcortical white matter, the left thalamus, and the right cerebral peduncle. Her vision improved dramatically after steroid therapy; however, 3 months after the 1st episode, she developed acute encephalopathy with extensive newly developed ADEM-like lesions and resolution of previous hyperintensities. Despite regular interferon β-1a injection after steroid tapering, she developed a 3rd episode presenting as a right ON. Throughout these three episodes, serological tests associated with autoimmune diseases, viral markers, anti-aquaporin-4 antibodies, and cerebrospinal fluid oligoclonal bands were negative, with the immunoglobulin G index in the normal range. After the 3rd episode, anti-MOG antibody testing was performed and higher titer was detected. Testing for anti-MOG antibodies is highly recommended for relapsing inflammatory demyelinating central nervous system diseases in pediatric patients, in order to define early an adequate long-term treatment.

Serum concentrations of α2-macroglobulin, α1-antitrypsin, and C-reactive protein in dogs with suspected acute pancreatitis

In canine acute pancreatitis (AP), inappropriate release and activation of zymogen proteases within the pancreas results in the consumption of serum antiproteases. The aim of this study was to examine whether the serum concentrations of α₂-macroglobulin (A2MG), α₁-antitrypsin (A1AT), and C-reactive protein (CRP) differ between dogs with AP and healthy dogs. Twenty healthy dogs and 20 dogs with AP were included in this study. Concentrations of A2MG, A1AT, and CRP were measured in the sera of healthy dogs and dogs diagnosed with AP. Serum A2MG and A1AT concentrations were significantly lower in dogs with AP than in healthy dogs, whereas the serum CRP concentration was significantly higher. In addition, the concentrations of A2MG and A1AT were significantly higher in AP survivors than in AP non-survivors, while the CRP concentration was significantly lower. However, in both AP survivors and non-survivors, the CRP concentrations showed a negative correlation with A2MG concentrations but not with A1AT. These findings indicate that serum antiproteases and CRP concentrations might be associated with the mortality rate of AP in dogs.

Survey of Oral Health Education Effects in Twenties / 대한소아치과학회지

The purpose of this study was to improve efficacy of oral health education in children and adolescents based on the experience and perception of oral health education in young adults who graduated from high school within 10 years.Questionnaires were given to 412 people, and among them, 388 completed survey forms were selected. The questionnaire included categories which examined one's experience and perception of oral health education, oral health knowledge, dental history, and oral health behavior.The results showed that the respondents perceived elementary school as the most effective period of oral health education. Oral examination with direct explanation was the most preferred method of oral health education, but web search was the main source of oral health information. And knowledge of fluoride and sealant about caries preventive effect was still lacking. Considering these results, oral examination with direct explanation and web search would be useful to improve efficacy of oral health education in children and adolescents.

Prosthetic Valve Endocarditis caused by HACEK Organisms: a Case Report and Systematic Review of the Literature

HACEK is a rare cause of prosthetic valve endocarditis (PVE). We describe 42-year-old male patient who presented with Aggregatibacter aphrophilus PVE and cerebral infarct. A. aphrophilus was isolated from his blood cultures as the sole pathogen, which was confirmed by subsequent 16S rRNA sequencing. He was treated with valve replacement surgery and an 8 week course of pathogen-directed antibiotic therapy and followed for 20 months without recurrence.

Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice

BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR. RESULTS: The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatory Casp1 (Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated gene Ndufb9 (NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group. CONCLUSIONS: HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses of Casp1 and Ndufb9 were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions of Casp1 and Ndufb9 in liver were regulated by their methylation statuses.

Similarity Analysis of Korean Medical Literature and Its Association with Efforts to Improve Research and Publication Ethics

In the present study, the frequency of research misconduct in Korean medical papers was analyzed using the similarity check software iThenticate®. All Korean papers written in English that were published in 2009 and 2014 in KoreaMed Synapse were identified. In total, 23,848 papers were extracted. 4,050 original articles of them were randomly selected for similarity analysis. The average Similarity Index of the 4,050 papers decreased over time, particularly in 2013: in 2009 and 2014, it was 10.15% and 5.62%, respectively. And 357 (8.8%) had a Similarity Index of ≥ 20%. Authors considered a Similarity Index of ≥ 20% as suspected research misconduct. It was found that iThenticate® cannot functionally process citations without double quotation marks. Papers with a Similarity Index of ≥ 20% were thus individually checked for detecting such text-matching errors to accurately identify papers with suspected research misconduct. After correcting text-matching errors, 142 (3.5% of the 4,050 papers) were suspected of research misconduct. The annual frequency of these papers decreased over time, particularly in 2013: in 2009 and 2014, it was 5.2% and 1.7%, respectively. The decrease was associated with the introduction of CrossCheck by KoreaMed and the frequent use of similarity check software. The majority (81%) had Similarity Indices between 20% and 40%. The fact suggested that low Similarity index does not necessarily mean low possibility of research misconduct. It should be noted that, although iThenticate® provides a fundamental basis for detecting research misconduct, the final judgment should be made by experts.