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The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage.

Summary: Cholangiocarcinoma (CCA) is rare cancer with the highest incidence in Eastern and Southeast Asian countries. Advanced CCA patients rely on chemotherapeutic regimens that offer unsatisfied clinical outcomes. We developed a comprehensive drug response profiling to investigate potential new drugs using CCA cell lines from Thai and Japanese patients against 100 approved anti-cancer drugs. We identified two major CCA subgroups that displayed unique molecular pathways from our integrative pan-omic and ligand-induced pathway activation analyses. MEK and Src inhibitors specifically killed the CCA1 subgroup without causing cytotoxicity to the normal cholangiocyte. Next, we developed the CCA45 signature to classify CCA patients based on their transcriptomic data. Our CCA45 signature could accurately predict prognosis, especially for Asian CCA patients. Our study provides a comprehensive public resource for drug repurposing in CCA and introduces analytical strategies for prioritizing cancer therapeutic agents for other rare cancer.

Objective: To compare academic outcomes between integrated flipped classroom (FC) and solely traditional lecture (TL) teaching approach among 2nd year medical students in Epidemiology and Biostatistics course. Methods: General information and academic achievements including grade point average, scores of the basic statistics course and scores of Epidemiology and Biostatistics course were extracted from the database of the Education Department. The records were excluded if they belonged to repeated or transferred students. The students in 2014 and 2015 academic year represented the TL group and the FC group respectively. The main outcome was the examination score from the two groups which was converted to a comparable scale out of a hundred. Results: Six-hundred twenty-eight records were included in the analysis. Based on independent t-test, the TL group showed higher mean score as compared to the FC group (p-value < 0.01). Further comparison using ANCOVA adjusted for age, gender, hometown location, high school location, grade point average and score of a basic statistics course showed a higher score in the TL group (p-value < 0.01). Conclusion: TL yielded higher examination score than FC from this retrospective study.

Objective: Electronic learning system (e-lecture) has been developed and used as a tool to assist students’ learning. Usage of e-lecture and learning behaviors were evaluated for their associations with learning outcomes. Methods: This questionnaire-based, cross-sectional study enrolled 107 first pre-clinical year medical students at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Information on learning outcomes of biomedical subjects and learning behavior including e-lecture use, self-study time, skipping class and inattention were collected. Mann-Whitney U test and logistic regression were used for statistical analysis. Results: Compared to students who earned average biomedical grades of >3.0, students who earned average grades ≤3.0 significantly used more e-lecture (median, IQR 63.81, 49.17-70.03 and 31.08, 11.29-51.49, respectively, p =0.001), had more inattention time during lectures (median, IQR, 22.13, 14.94-31.19, and 13.1, 8.05-20.30, respectively, p=0.008), and spent less time for self-study and review of lessons (median, IQR 102.00, 68.00-176.50, and 147.50, 106.25-246.00, respectively, p=0.04). For each one hour increase in e-lecture usage, the chance of earning an average biomedical grade of >3.0 was decreased by 4%. Positive correlations were found between e-lecture usage with skipping class and with inattention during lecture (coefficients = 0.31 and 0.37, with p=0.001 and p

Background: Medical students who will grow up as physicians will be role models for patients in health behaviors. However, some medical students are still overweight or obese. A weight reduction program can both decrease weight and change attitude about obesity and losing weight. Unfortunately, there is no validated questionnaire to measure knowledge and attitude about obesity and weight loss for our medical students. Objective: To develop a questionnaire for evaluation of knowledge and attitude toward obesity and weight loss in Thai overweight/obese medical students. Methods: We developed the questionnaire using Health Belief Model under consultation of two experts in obe- sity, biostatistics and epidemiology. Validity of the questionnaire was evaluated by the index of item-objective congruence under supervision of five experts. This pilot study was performed to test the internal consistency and reliability using Cronbach’s alpha coefficient. Twenty-seven medical students who self-reported as overweight or obese were included in this study. Results: A fifty-seven items questionnaire using five-point Likert scale was developed with the index of item- objective congruence of all items in presented questionnaire more than 60%. Cronbach’s alpha coefficients of all domains were in the range of 0.74-0.90 and overall standardized Cronbach’s coefficient of the questionnaire was 0.87. The average inter-item correlation of each domain was in acceptable range (0.21-0.62) although; those of the total scale were 0.12. Conclusion: Validity and reliability of this questionnaire were acceptable to be used for assessment of knowledge and attitude of obesity and losing weight in Thai overweight or obese medical students.

The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage.

Cholangiocarcinoma (CCA) is rare cancer with the highest incidence in Eastern and Southeast Asian countries. Advanced CCA patients rely on chemotherapeutic regimens that offer unsatisfied clinical outcomes. We developed a comprehensive drug response profiling to investigate potential new drugs using CCA cell lines from Thai and Japanese patients against 100 approved anti-cancer drugs. We identified two major CCA subgroups that displayed unique molecular pathways from our integrative pan-omic and ligand-induced pathway activation analyses. MEK and Src inhibitors specifically killed the CCA1 subgroup without causing cytotoxicity to the normal cholangiocyte. Next, we developed the CCA45 signature to classify CCA patients based on their transcriptomic data. Our CCA45 signature could accurately predict prognosis, especially for Asian CCA patients. Our study provides a comprehensive public resource for drug repurposing in CCA and introduces analytical strategies for prioritizing cancer therapeutic agents for other rare cancer., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Cholangiocarcinoma (CCA) is a bile duct cancer with a very poor prognosis. Currently, there is no effective pharmacological treatment available for it. We showed that CCA ubiquitously relies on cyclin-dependent kinases 4 and 6 (CDK4/6) activity to proliferate. Primary CCA tissues express high levels of cyclin D1 and the specific marker of CDK4/6 activity, phospho-RB Ser780. Treatment of a 15-CCA cell line collection by pharmacological CDK4/6 inhibitors leads to reduced numbers of cells in the S-phase and senescence in most of the CCA cell lines. We found that expression of retinoblastoma protein (pRB) is required for activity of the CDK4/6 inhibitor, and that loss of pRB conferred CDK4/6 inhibitor-drug resistance. We also identified that sensitivity of CCA to CDK4/6 inhibition is associated with the activated KRAS signature. Effectiveness of CDK4/6 inhibition for CCA was confirmed in the three-dimensional spheroid-, xenograft-, and patient-derived xenograft models. Last, we identified a list of genes whose expressions can be used to predict response to the CDK4/6 inhibitor. Conclusion: We investigated a ubiquitous dependency of CCA on CDK4/6 activity and the universal response to CDK4/6 inhibition. We propose that the CDK4/6-pRB pathway is a suitable therapeutic target for CCA treatment., (© 2019 by the American Association for the Study of Liver Diseases.)

Competing Interests: Competing interests: None declared.

Millions of people, worldwide, struggle with being overweight or obese. Medical students, who will eventually become physicians, should be good role models for patients; however, some medical students are themselves overweight or obese. The aim of this study was to evaluate the efficacy of a weight-loss program for medical students in Thailand. A six-month weight reduction program was designed consisted of three full-day sections that were scheduled, as follows: Day One, End of Week One, and End of Week Eight. The interventions incorporated various behavior modification strategies. Participant anthropometric measurements were recorded. Obesity-related knowledge, perception, attitude, and inappropriate weight-loss behaviors were obtained by validated questionnaire. At the end of the study, statistically significant weight loss was demonstrated (median 2.70 kg, p<0.05) compared to baseline. Moreover, participant knowledge significantly increased and inappropriate weight-loss behaviors significantly decreased (p<0.05 and p<0.05, respectively) compared to baseline. Given the demonstrated modest effectiveness of this low-intensity weight reduction program, this intervention should be considered as an effective education tool for medical students.