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Purpose: This study aims to raise awareness of the disparities in survival predictions among races in head and neck cancer (HNC) patients by developing and validating population-based prognostic models specifically tailored for Taiwanese and Asian populations. Methods: A total of 49,137 patients diagnosed with HNCs were included from the Taiwan Cancer Registry (TCR). Six prognostic models, divided into three categories based on surgical status, were developed to predict both overall survival (OS) and cancer-specific survival using the registered demographic and clinicopathological characteristics in the Cox proportional hazards model. The prognostic models underwent internal evaluation through a tenfold cross-validation among the TCR Taiwanese datasets and external validation across three primary racial populations using the Surveillance, Epidemiology, and End Results database. Predictive performance was assessed using discrimination analysis employing Harrell's c-index and calibration analysis with proportion tests. Results: The TCR training and testing datasets demonstrated stable and favorable predictive performance, with all Harrell's c-index values ≥ 0.7 and almost all differences in proportion between the predicted and observed mortality being < 5%. In external validation, Asians exhibited the best performance compared with white and black populations, particularly in predicting OS, with all Harrell's c-index values > 0.7. Conclusions: Survival predictive disparities exist among different racial groups in HNCs. We have developed population-based prognostic models for Asians that can enhance clinical practice and treatment plans. [ABSTRACT FROM AUTHOR]

The ability of medical students to speak up before a medical error occurs is a timely and necessary interaction to prevent potential patient harm. As it may be crucial to improve patient safety, we explored how medical students react to a medical error and provided them appropriate training regarding speaking up about medical issues. A quasi-experimental study was conducted in Taiwan involving 153 medical students who participated in a speaking-up simulation course. They were divided into two groups. The first group participated in a non-life-threatening scenario before the intervention, followed by a personalized debriefing session, then a life-threatening scenario after the intervention. The second group participated in a life-threatening scenario before the intervention, followed by a personalized debriefing session, then a non-life-threatening scenario after the intervention. Students also completed patient safety attitude survey. During the preintervention scenario, the overall medical students' speaking-up rate to medical error was 45.1%. The speaking-up rate of medical students in life-threatening scenario was significantly higher than the rate in non-life-threatening scenario before the intervention (64.6% vs 24.3%, p < 0.001). After personalized debriefing, the speaking-up rate to medical errors was significantly improved both in life-threatening scenarios (95.9%, p < 0.001) and in non-life-threatening scenarios (100%, p < 0.001). Male medical students had significantly higher speaking-up rates than female students in life-threatening scenario (76.2% vs 51.4%, p = 0.02). On post-intervention surveys, students provided several reasons for their likelihood of speaking up or remaining silent during a medical error event. Medical students' rate of speaking-up to medical error was higher in a simulated life-threatening scenario than in a simulated non-life-threatening scenario. Faculty-led personalized debriefing can facilitate medical students' adoption of communication strategies to speak up more in medical error events. Educators should also consider gender differences when they design effective assertive communication courses. Practice points Personalized assertive communication training could improve medical students speaking up behavior in the event of medical error. The medical students have a higher rate of speaking up in the life-threatening scenario compared to the non-life-threatening scenario. Male students had a higher rate of speaking up than females in the life-threatening scenario but not in the non-life-threatening scenario. [ABSTRACT FROM AUTHOR]

Training medical students to speak up when they witness a potential error is an important competency for patient safety, but details regarding the barriers that prevent medical students from effectively communicating are lacking. Therefore, this study aimed at exploring the factors affecting medical students' willingness to speak up for patient safety when a medical error was observed. This is a cross-sectional study at a medical university in Taiwan, and 151 medical students in clinical clerkship completed a survey including demographic characteristics, conflict of interests/social relationship, personal capability, and personality and characteristics of senior staff domains. Data were analyzed using t-test. Three of five items in the conflict of interests/social relationship domain showed statistically significant importance, including 'I am afraid of being punished' (Mean difference, MD = 0.37; p < 0.01), 'I do not want to break unspoken rules' (MD = 0.55; p < 0.01), and 'I do not want to have bad team relationship' (MD = 0.58; p < 0.01). Two items (perception of knowledge/understanding and communication skills) in the personal capability domain were significantly important to speaking up. Six of 10 items in personality and characteristics of senior staff domain were rated significantly important in deciding to speak up. The top three factors of them were senior personnel with 'Grumpy' personality (MD = 1.20; p < 0.01), 'hierarchy gap' (MD = 1.12; p < 0.01), and senior personnel with 'Stubborn' personality (MD = 1.06; p < 0.01). Our findings demonstrated medical students' perspectives on barriers to speaking up in the event of medical error. Some factors related to characteristics of senior staff could compromise medical students' ability to speak up in the event of medical error. These results might be important for medical educators in designing personalized educational activities related to medical students' ability to speak up for patient safety. [ABSTRACT FROM AUTHOR]

Background: It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations. Methods: This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2). Results: From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age. Conclusion: This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common malignant cancers due to poor prognoses and high mortality rates worldwide. However, an effective chemotherapeutic drug without side effects remains lacking. Saussurea involucrata (SI) Kar. et Kir., also known as snow lotus, grows in mountainous rocky habitats at 2600 m elevation in the Tian Shan and Aer Tai regions of China. The ethyl acetate extract of SI had been shown to inhibit proliferation and induce apoptosis in various tumor cells. In this study, we demonstrated that Hispidulin, active ingredients in SI, inhibits the growth of AGS gastric cancer cells. After Hispidulin treatment, NAG-1 remained highly expressed, whereas COX-2 expression was downregulated. Flow cytometric analysis indicated that Hispidulin induces G1/S phase arrest and apoptosis in time- and concentration-dependent manners. G1/S arrest correlated with upregulated p21/WAF1 and pl6 and downregulated cyclin D1 and cyclin E, independent of p53 pathway. In addition, Hispidulin can elevate Egr-1 expression and ERK½ activity, whereas ERK½ inhibitor markedly attenuated NAG-1 mediated apoptosis. Taken together, Hispidulin can efficiently activate ERK½ signaling followed by NAG-1 constitutive expression and trigger cell cycle arrest as well as apoptosis in cancer cell. It can be a potential compound for combination therapy of gastric cancer in the future. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with advanced and recurrent EGFR-positive non-small cell lung cancer., Objective: The main objective of the present study was to compare the clinical efficacies between osimertinib and afatinib as first-line treatment in patients with EGFR-mutant non-small cell lung cancer., Methods: We retrospectively analyzed patients with advanced and recurrent non-small cell lung cancer who harbored an exon 19 deletion or an exon 21 L858R mutation and were being given either osimertinib or afatinib as first-line treatment from January 2018 to December 2020., Results: A total of 128 patients were selected for this study. The osimertinib group included 47 patients, while 81 patients received afatinib. The median follow-up time was 20.1 months in the osimertinib group and 22.7 months in the afatinib group. The median progression-free survival was 18.8 months and 13.1 months in the osimertinib and afatinib groups, respectively (hazard ratio 0.75 [95% confidence interval 0.48-1.18]). The median overall survival was not reached in the osimertinib group and was 41.7 months in the afatinib group (hazard ratio 0.79 [95% confidence interval 0.36-1.72]). In patients without brain metastasis, the median progression-free survival was 17.9 months and 17.2 months in the osimertinib and afatinib groups, respectively (hazard ratio 1.02 [95% confidence interval 0.56-1.85]). In patients with brain metastasis at baseline, the median progression-free survival was 22.1 months in the osimertinib group, and 10.9 months in the afatinib group (adjusted hazard ratio 0.45 [95% confidence interval 0.21-0.96])., Conclusions: Our research demonstrates that there was no strong evidence showing that patients taking osimertinib as first-line treatment experienced longer median progression-free survival and overall survival than patients treated with afatinib. However, there was a statistical significance revealing that osimertinib provided better median progression-free survival than afatinib in patients with brain metastasis at baseline., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Today, flipped classroom (FC) has been widely used in medical education. However, the effectiveness of FC remains controversial. The variation may cause by different subjects or different course design. Moreover, those studies did not explain how the association among different domains of learning objective was in FCs. The purpose of this study was to explore the help of learning domains from a FC of suturing skill in year-5 medical students., Design: This study determined sample size according to statistical power. A minimum number of 77 participants for regression analysis are needed. Therefore, this study enrolled 78 medical students in a 2-hour suturing course, which consisted of pre-class video and in-class instruction. Both simple and mattress suturing were taught. The students received an anonymous survey with questionnaire of Help from Instruction Questionnaire for Clinical Skills (HIQ-CS) after the course. The HIQ-CS was developed by medical education team according to Bloom's taxonomy, and its reliability was favorable (Cronbach's ^l = 0.839). Factor loadings among all items in the HIQ-CS was also favorable (0.790 to 0.849). This study determined consensus of students' perspective by median (Me) and interquartile range (IQR), and tested mediation among different learning domains by regression., Results: The results showed medical students agreed FC can help them in learning suturing (Me = 4, IQR = 1). The cognitive help (β = .526, p < .001) was completely mediated by psychomotor help (β = .399, p < .001) and affective help (β = .413, p < .001) to overall helps in FC. The affective help (β = .617, p < .001) was partially mediated by psychomotor help to overall helps in FC., Conclusions: FC may help students in learning suturing skill in different domains. Our model explains the cognitive help from FC provides an important foundation for the helps of other domains. Although the model should be examined by different curricula and measurements in future, the model of help from instruction in our study provided an innovated concept and framework in medical education., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the effectiveness of a simulation-based flipped classroom in gaining the laparoscopic skills in medical students., Design: An intervention trial., Setting: Taipei Medical University Hospital, an academic teaching hospital., Participants and Methods: Fifty-nine medical students participating in a 1-hour laparoscopic skill training session were randomly assigned to a conventional classroom (n = 29) or a flipped classroom approach (n = 30) based on their registered order. At the end of the session, instructors assessed participants' performance in laparoscopic suturing and intracorporeal knot-tying using the assessment checklist based on a modified Objective Structured Assessment of Technical Skills tool., Results: Students in the flipped group completed more numbers of stitches (mean [M] = 0.47; standard deviation [SD] = 0.507) than those in the conventional group (M = 0.10; SD = 0.310) (mean difference: 0.37; 95% CI: 0.114-582; p = 0.002). Moreover, students in the flipped group also had higher stitch quality scores (M = 7.17; SD = 2.730) than those in the conventional group (M = 5.14; SD = 1.767) (mean difference = 2.03; 95% CI: 0.83-3.228; p = 0.001). Meanwhile, students in the flipped group had higher pass rates for the second throw (p < 0.001), third throw (p = 0.002), appropriate tissue reapproximation without loosening or strangulation (p < 0.001), needle cut from suture under direct visualization (p = 0.004), and needle safely removed under direct visualization (p = 0.018) than those in the conventional group., Conclusions: Comparing with traditional approach, a simulation-based flipped classroom approach may improve laparoscopic intracorporeal knot-tying skill acquisition in medical students., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer. Experimental Design: FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro cellular assays and in vivo mouse models. In addition, the N-glycosylation-defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression. Results: We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities in vitro FAM198B also attenuated tumor growth and metastasis in vivo We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability. Conclusions: Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma. Clin Cancer Res; 24(4); 916-26. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Purpose: Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential., Patients and Methods: Whole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities., Results: YAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells., Conclusion: These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management., (© 2015 by American Society of Clinical Oncology.)

Background: Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction., Methods: Advanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens., Results: A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6-11.0) and 20.5 months (95% CI 15.1-26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13-24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33-2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04-3.18], p = 0.036)., Conclusion: Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.

Rationale: Despite advances in treatment and prognosis of non-small cell lung cancer (NSCLC), patient outcomes are still unsatisfactory., Objectives: To reduce the morbidity and mortality of patients with NSCLC, a more comprehensive understanding of mechanisms involved in cancer progression is urgently needed., Methods: By comparison of gene expression profiles in the cell line pair with differential invasion ability, CL1-0 and CL1-5, we found that Shisa3 was highly expressed in the low invasive cells. The effect of Shisa3 on invasion, migration, proliferation, apoptosis, epithelial-mesenchymal transition, and anchorage-independent growth activities in vitro and on tumor growth and metastasis in mice models were examined. The underlying mechanism of Shisa3 was explored by microarray and pathway analysis. Finally, the correlation of Shisa3 expression and clinical outcome was also calculated., Measurements and Main Results: We identified Shisa3 as a novel tumor suppressor, which induces β-catenin degradation resulting in suppression of tumorigenesis and invasion in vitro. Shisa3 decreased the tumor growth in mice with subcutaneous implantation and reduced the number of metastatic nodules in mice with tail vein injection and orthotopic implantation. Shisa3 performs the tumor suppression activity through WNT signaling predicted by microarray analysis. Our data found that Shisa3 accelerates β-catenin degradation and was positively associated with overall survival and progression-free survival of NSCLC., Conclusions: Our results reveal that Shisa3 acts as a tumor suppressor by acceleration of β-catenin degradation and provide new insight for cancer prognosis and therapy.