Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study.

The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).

Transtheoretical model to predict the stages of changes in smoking cessation behavior among adolescents.

Introduction: Previous studies on adolescent smoking cessation behavior based on the transtheoretical model have primarily focused on the development of cessation programs. Attempting to quit smoking is a prerequisite for executing smoking cessation. Appropriate methods must be selected based on the characteristics and intentions of individuals to increase smokers' satisfaction and success rates in quitting. Therefore, this study aimed to identify changing processes influencing the stages of change associated with successful smoking cessation among adolescents and examined the related factors. This descriptive study explored a transtheoretical model of different stages of changes in smoking cessation behavior among adolescent smokers. Methods: The participants included 237 middle and high school students in South Korea. We examined the differences in stages of changes in smoking cessation behaviors based on general characteristics, smoking-related characteristics, smoking cessation change processes (cognitive and behavioral), smoking decisional balance (pros and cons of smoking), and self-efficacy. Results: The probability of reaching the preparation stage of smoking cessation was significantly lower among participants who did not know their father's educational level than among those who knew their father's educational level. Conversely, this probability was significantly higher among participants whose mothers had a college or higher education level and those who did not know their mother's educational level than in those whose mothers had a high school or lower education level. Conclusion: These findings indicated that parental education is a significant predictor of the preparation stage of smoking cessation, highlighting the importance of the family environment in facilitating smoking cessation among adolescents. Accordingly, communication and support at home could help reinforce adolescents' determination to quit smoking and make relevant plans. Thus, smoking cessation support should stress the need to enhance communication at home.

CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice.

Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47nullRag2nullIL-2rγnull (RTKO) mice, and applied it to generate humanized mice. Methods: Four-week-old female NOD-Rag2nullIL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results: For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion: Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields.

Paleoparasitological surveys for detection of helminth eggs in archaeological sites of Jeolla-do and Jeju-do.

A paleoparasitological survey to detect helminth eggs was performed in archaeological sites of Jeolla-do and Jeju-do, the Republic of Korea. Total 593 soil samples were collected in 12 sites of Jeolla-do and 5 sites of Jeju-do from April to November 2011, and examined by the methods of Pike and coworkers. A total of 4 helminth eggs, 2 eggs each for Trichuris trichiura and Ascaris sp., were found in soil samples from 1 site, in Hyangyang-ri, Jangheung-eup, Jangheung-gun, Jeollanam-do. The egg-recovery layer was presumed to represent a 19th century farm, which fact suggested the use of human manures. This is the third archaeological discovery of parasite eggs in Jeolla-do. Additionally, no helminth eggs in archaeological sites of Jeju-do is an interesting problem to be solved in the further investigations.

Examining Factors Associated with E-Cigarette Use among Current Smokers.

We present a secondary data analysis of the raw data from the eighth Korea National Health and Nutrition Examination Survey (KNHANES). A total of 827 current smokers who responded that they had smoked >5 packs (100 cigarettes) of cigarettes in their lifetime and were currently smoking traditional cigarettes were selected. This study was conducted to identify sociodemographic, smoking-related, and health-related characteristics that influence the use of e-cigarettes in adult smokers. To examine these factors, general characteristics such as age, marital status, education level, and occupation were included in Model 1, while health-related characteristics such as the level of smoking and depression were included in Model 2. In Model 1, age, a high level of education, and working in an office were found to be significantly correlated with e-cigarette use among smokers, while age and working in the office were found to be significantly correlated with e-cigarette use in Model 2. Therefore, e-cigarette use was high among adult smokers of young ages who were office workers. Although evidence is lacking regarding its safety and use as smoking cessation aids, many smokers have been reported to use e-cigarettes as smoking cessation aids, making it necessary to provide accurate information on e-cigarettes.

Factors Related to the COVID-19 Prevention Behaviors of Adolescents: Focusing on Six Middle and High Schools in Korea.

The COVID-19 pandemic has been one of the worst infectious disasters in human history. The best way to minimize COVID-19 transmission is to follow preventive measures. This study aimed to examine the factors influencing adolescents' COVID-19 prevention behaviors. The study was conducted online from 1 to 15 February 2023 with 196 adolescents aged between 13 and 18 years of age. The collected data were analyzed using descriptive statistics, Pearson's correlation, the independent t-test, analysis of variance (ANOVA), and multiple hierarchical regression analysis. Adolescents' COVID-19 prevention behaviors were influenced by intrapersonal factors, such as knowledge of and attitudes toward COVID-19, and interpersonal factors, such as social support. Community and governmental factors had no impact. Public health education strategies should be planned to include friends and family members in programs for preventing new infectious diseases such as COVID-19 so that adolescents can learn and share what they have learned, correct wrong behavior, and understand and change infection prevention behavior. In addition, it is necessary to actively support the development of public health education with appropriate contents in accordance with the characteristics and preferences of adolescents.

Impact of Self-Control and Social Network of Friends on the Amount of Smoking among Out-of-School Youth.

The aim of this study is to understand the effects of self-control and social networks of friends on the amount of smoking among out-of-school adolescents. The subjects of this study were 187 out-of-school adolescent smokers from the J-province Youth Counseling Welfare Center as of 2020. Data were collected through self-report questionnaires that contained questions about sociodemographic characteristics, self-control, social networks of friends, and amount of smoking. The dependent variable was smoking amount. Descriptive statistics, χ2 tests, correlation analyses, and regression analysis were performed. The predictors of smoking in OSY (out-of-school youth) were analyzed with respect to self-control and social networks of friends. The significant variables in model 3 were age, living with parents, and average allowance. The smoking rate of friends (ß = 0.256) and the degree of penetration of friends smoking (ß = 0.341) were significant variables. The higher the percentage of friends smoking and the higher the degree of penetration of smoking among the members of social networks, the higher the amount of smoking.

Smartphone Use Type, Fear of Missing Out, Social Support, and Smartphone Screen Time Among Adolescents in Korea: Interactive Effects.

This study aims to examine the relationship between intrapersonal factors, interpersonal factors, smartphone screen time, and the moderating roles of interpersonal factors, on the basis of the ecological model. This study is a cross-sectional and descriptive study. A total of 428 participants from four public middle schools were selected through convenience sampling (55.1% female; Mean age 13.0 ± 0.78). Data were collected through self-report questionnaires that contained questions about sociodemographic characteristics, intrapersonal factors (types of smartphone use, Fear of missing out-FoMO), interpersonal factors (support from parents, teachers, and peers), and smartphone screen time. The collected data were analysed using descriptive statistics, t-test, ANOVA, Pearson's correlation coefficients, and hierarchical regression. The daily smartphone screen time was 4.05 ± 2.16 h. Results showed that social media (ß = 0.155), games (ß = 0.140), and FoMO (ß = 0.227) were positively associated with smartphone screen time, while educational videos (ß = -0.130) and parental support (ß = -0.212) were negatively associated with smartphone screen time. Peers support moderated the association between games and smartphone screen time. Parental support moderated the association between educational videos, videos/movies/TV, and smartphone screen time. The findings highlight the direct and interactive roles of intrapersonal and interpersonal factors in predicting adolescents' smartphone screen time. Based on this study, the intrapersonal and interpersonal factors of adolescents should be comprehensively considered to intervene in their proper smartphone use.

A Study on the COVID-19 Preventive Behaviors of Automobile Manufacturing Workers in South Korea.

The present study used a cross-sectional, descriptive survey design to investigate the influencing factors of COVID-19-related infection prevention behaviors of workers in the automobile manufacturing sector. An online survey was conducted on 157 workers in the automobile manufacturing sector of a company in Korea. We analyzed the collected data using SPSS to test whether there were significant differences in COVID-19 risk perception, crisis communication, health literacy, and infection prevention behaviors according to the general characteristics of the participants. An independent sample t-test and a one-way analysis of variance (ANOVA) were performed. A Pearson's correlation analysis was performed to identify the correlations among COVID-19 risk perception, crisis communication, health literacy, and infection prevention behaviors. Multiple regression analysis was performed to identify the influencing factors of COVID-19 infection prevention behaviors. The regression model was found to be significant, and the employment period at current job, COVID-19 prevention education, source of information, COVID-19 risk perception, crisis communication, and health literacy were also found to be significant. Among the demographic variables, employment period at current job of 5−10 years showed a higher level of infection prevention behaviors than that of <5 years. Moreover, the level of infection prevention behaviors was also significantly higher when COVID-19-related information was acquired through the KDCA/health center. Higher COVID-19 risk perception, crisis communication, and health literacy were associated with significantly higher levels of infection prevention behaviors. Therefore, based on the results, health managers need to develop programs and educate and improve information comprehension and crisis communication skills in order to promote workers' infection prevention behaviors of emerging infectious diseases in an era of global change.

Factors Associated with Smoking Behaviors in Out-of-School Youth: Based on an Ecological Model.

PURPOSE: To investigate the association between smoking behavior in out-of-school youths (OSY) and individual, interpersonal, and organizational factors through an ecological model. METHODS: Participants were 297 OSY aged 13-18 years, who visited J area's counseling center. The independent variables were self-control (intrapersonal factor), parental attachment and social network (interpersonal factors), and exposure to no-smoking policy (community factor). The dependent variable was smoking. Descriptive statistics, χ2-tests, correlation analyses, and logistic regression analysis were performed. RESULTS: The predictors of smoking in OSY were analyzed using demographic, intrapersonal, interpersonal, and community factors. Period after discontinuation of school, self-control, parental attachment, and friends' smoking behavior were significant predictors. Smoking behavior was found to decrease when the period after discontinuation of school was over than one year, when the parents attachment increased and when self-control increased. Conversely, smoking increased when friends' smoking increased. CONCLUSIONS: When administering smoking prevention programs for OSY, parental attachment and psychological traits, such as self-control, should be taken into consideration. Therefore, for effective results, such programs need to strengthen self-control, stress the importance of parental attachment through parent education, and enroll adolescents along with their friends who smoke. Implications and Contribution: Based on an ecological model, this descriptive survey, conducted to investigate the association between smoking behavior among out-of-school youths and individual, interpersonal, and organizational factors, proposes that smoking prevention programs should consider parental attachment and psychological traits, including self-control, for optimal effectiveness.

Simultaneous quantification of six nonpolar ginsenosides in white ginseng by reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection.

BACKGROUND: White ginseng consists of the roots and rhizomes of the Panax species, and red ginseng is made by steaming and drying white ginseng. While red ginseng has both polar and nonpolar ginsenosides, previous studies showed white ginseng to have only polar ginsenosides. Because nonpolar ginsenosides are formed through the manufacture of red ginseng from white ginseng, researchers have generally thought that nonpolar ginsenosides do not exist in white ginseng. METHODS: We developed a simultaneous quantitative method for six nonpolar ginsenosides in white ginseng using reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection. The nonpolar ginsenosides of white ginseng were extracted for 4 h under reflux with 50% methanol. RESULTS: Using the gradient elution system, all target components were completely separated within 50 min. Nonpolar ginsenosides were determined in the rhizome head (RH), main root (MR), lateral root, and hairy root (HR) of 6-year-old white ginseng samples obtained from several regions (Geumsan, Punggi, and Kanghwa). The total content in the HR of white ginseng was 37.8-56.8% of that in the HR of red ginseng. The total content in the MR of white ginseng was 5.9-24.3% of that in the MR of red ginseng. In addition, the total content in the RH of white ginseng was 28.5-35.8% of that in the HR of red ginseng. CONCLUSION: It was confirmed that nonpolar ginsenosides known to be specific components of red ginseng were present at substantial concentrations in the HR or RH of white ginseng.

Compound mutations involving T315I and P-loop mutations are the major components of multiple mutations detected in tyrosine kinase inhibitor resistant chronic myeloid leukemia.

To analyze the pattern of multiple mutations detected by Sanger sequencing (SS), we performed subcloning sequencing using 218 samples from 45 patients with tyrosine kinase inhibitor resistant chronic myeloid leukemia. At the first time of multiple mutation detection by SS (baseline), a total of 19 major mutations from 45 samples were detected; these mutations were found in the following order: T315I (68.9%), E255 K (33.3%), Y253H (13.3%), G250E (13.3%), and F317 L (11.1%). Subcloning sequencing of 900 baseline colonies identified 556 different mutant types, and 791 among the 900 were colonies with major mutations (87.9%). The mutations were found in the following order: T315I (36.4%), E255 K (16.2%), Y253H (7.0%), G250E (6.7%), M351 T (6.6%), and E255 V (5.3%). In subcloning sequencing with 4357 colonies of 218 serial samples, 2506 colonies (57.5%) had compound mutations, among which 2238 colonies (89.3%) had at least one major mutation. The median number of mutations in compound mutant colonies was 2 (range, 2-7), and most were double (52.9%) or triple (28.7%) mutations. Additionally, some mutations in allosteric binding sites were detected as low level mutation in 13 patients. With the available retrospective samples before baseline, subcloning sequencing identified low-level mutations of various frequencies (median, 10%) to be major mutations in 20 patients. Thus, compound mutations involving T315I and P-loop mutations were the major components of multiple mutations, and some low-level mutations with potential clinical significance were detected by subcloning sequencing. Hence, more sensitive sequencing assays are needed in patients with multiple mutations.

Baseline BCR-ABL1 transcript type of e13a2 and large spleen size are predictors of poor long-term outcomes in chronic phase chronic myeloid leukemia patients who failed to achieve an early molecular response after 3 months of imatinib therapy.

We conducted this study to identify the factors for predicting poor outcomes in chronic myeloid leukemia patients who failed to achieve a 3-month early molecular response (EMR). Of the 413 newly diagnosed, chronic phase, chronic myeloid leukemia patients receiving imatinib (IM), 120 (29.1%) failed to achieve a 3-month EMR. With a median follow-up of 67.0 months, 39 patients continued IM treatment with at least complete cytogenetic response (CCyR), and 81 patients permanently discontinued IM treatment. The cumulative incidence rates of CCyR and major molecular response (MMR) by 3 years were 90.1 ± 3.9% and 53.7 ± 7.3%, respectively. After adjusting for potential factors, multivariate analyses showed that a transcript type of e13a2, compared with e14a2, and a larger spleen size were independent factors for failure of overall MMR. The predictive factors outlined in this study may provide valuable information for high-risk patients who would benefit from early decision-making regarding therapy change.

BCR-ABL1 transcript levels at 4 weeks have prognostic significance for time-specific responses and for predicting survival in chronic-phase chronic myeloid leukemia patients treated with various tyrosine kinase inhibitors.

The present study aimed to assess the clinical impact of BCR-ABL1 transcript levels determined at an earlier time point than the 3-month early molecular response (EMR) in chronic-phase chronic myeloid leukemia (CML-CP) patients. BCR-ABL1 transcript levels of CML-CP patients (n = 258; median age, 43 [range, 18-81] years) treated with various tyrosine kinase inhibitors (TKIs) were determined at 4 weeks (28 ± 3 days) and at every 3 months of treatment initiation. At 4 weeks, receiver operating characteristic curves revealed that cutoff values of BCR-ABL1 transcripts for achieving major molecular responses (MMRs) by 12 and 60 months were 40.89% and 39.16%, respectively (95% CI, 0.658-0.772 and 95% CI, 0.643-0.758; P < 0.0001). With 40% of BCR-ABL1 transcripts at 4 weeks (very early MR; VEMR), patients with VEMR achieved higher 3-month EMR and 4-week VEMR significantly associated with higher cumulative incidences of 5-year MMR (89.1% vs 72.3%; P < 0.001) and 5-year deep molecular response (DMR) (56.5% vs 29.4%; P = 0.001). Furthermore, event-free survival (EFS)-a (93.0% vs 84.8%; P = 0.068) and EFS-b (71.1% vs 57.9%; P = 0.061) by 5 years were also marginally significant. VEMR and 3-month EMR were achieved in 89 patients, with significantly superior outcomes. In multivariate analyses, lower leukocyte count (P = 0.008) and frontline second-generation TKI therapy size (P < 0.001) were significantly associated with VEMR achievement, but not baseline BCR-ABL1 level and CML duration. In conclusion, the 4-week BCR-ABL1 transcript levels including VEMR could be important to predict long-term outcomes and may provide additional information about innate intrinsic sensitivity to CML among individuals.

BCR-ABL1 transcripts (MR4.5) at post-transplant 3 months as an early predictor for long-term outcomes in chronic myeloid leukemia.

BACKGROUND/AIMS: The aim of this study was to identify the role of BCR-ABL1 transcript level as a predictor for post-transplant relapse and outcome in patients who underwent allogeneic stem cell transplantation (SCT) for chronic phase (CP) chronic myeloid leukemia (CML). METHODS: Of 101 patients receiving allograft in CML CP, 85 had available quantitative reverse transcriptase polymerase chain reaction data at post-transplant 3 months. These patients were divided into two groups according to molecular response (MR4.5), defined as a BCR-ABL1 transcript level ≤ 0.0032% on the international scale, at 3 months based on receiver operating characteristic curve analysis of relapse. RESULTS: The 4-year overall survival and event-free survival (EFS) were 80.6% and 57.3%, respectively, and the cumulative incidence of relapse at 4 years was 29.6% after a median follow-up of 126.4 months. We performed multivariate analyses including potential variables to evaluate the early predictive role of MR4.5 at 3 months and found that MR4.5 at 3 months was associated with a higher EFS (p = 0.028) and showed a trend for a lower relapse rate (p = 0.089). CONCLUSIONS: our results imply that frequent molecular monitoring and immune suppressive therapy modulation are required for patients without reduction of BCR-ABL1 transcripts to this level after SCT.

Distinct predictive factors influence on achievement of early molecular response by frontline imatinib in chronic phase chronic myeloid leukemia.

To explore the factors for achieving early molecular responses (EMR; BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months) by imatinib (IM), baseline characteristics including individual BCR-ABL1 transcript level, dose intensity, and IM trough level on day 29 were analyzed in 286 chronic phase chronic myeloid leukemia patients. Distinct predictive factors for achieving EMR at 3 months and 6 months were noted. Blast count at diagnosis and IM trough level on day 29 were significantly associated with an achievement of 3-month EMR. Early decline of BCR-ABL1 transcript, low Sokal risk, and mean daily dose (≥350mg/day) by 6 months were associated with an achievement of 6-month EMR. Understanding the predictive factors for EMR may provide additional information to guide clinical decisions on the changing therapies at each landmark.