Objective:To conduct simulated graduation skill assessment and annual skill assessment by self-designed objective structured clinical examination (OSCE) for standardized training of radiation oncology residents.Methods:The structured examination, standardized questions and standardized tasks of each disease were designed by teaching team of radiation oncology in the University of Hong Kong-Shenzhen Hospital. The implementation effect of the annual assessment and simulated completion assessment of standardized training for residents in radiation oncology from Class 2019 to 2021 was prospectively observed. The difference between scores by two independent examiners was analyzed by the paired t-test. The overall feedback of residents and examiners for the implementation were collected after the completion of OSCE. Results:A total of 18 residents participated in 67 sessions of 3-station skill assessments of different diseases, including 2 make-up tests. There was no difference in the score pairing and grade pairing tests between two examiners at 3 stations ( t=0.85, -0.68, -1.16; P=0.401, 0.499, 0.255). A total of 91.3% of the residents reported that the assessment well reflected their actual clinical competency. Conclusions:The current program of OSCE assessment for radiation oncology meets objectification, standardization and high efficiency, and achieves the goal of making trainers familiar with the graduation skill assessment and assessing comprehensive clinical competence. It is a reproducible and flexible structured assessment model.

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Objectives: With the sudden global shift to online learning modalities, this study aimed to understand the unique challenges and experiences of emergency remote teaching (ERT) in nursing education. Methods: We conducted a comprehensive online international cross-sectional survey to capture the current state and firsthand experiences of ERT in the nursing discipline. Our analytical methods included a combination of traditional statistical analysis, advanced natural language processing techniques, latent Dirichlet allocation using Python, and a thorough qualitative assessment of feedback from open-ended questions. Results: We received responses from 328 nursing educators from 18 different countries. The data revealed generally positive satisfaction levels, strong technological self-efficacy, and significant support from their institutions. Notably, the characteristics of professors, such as age (p = 0.02) and position (p = 0.03), influenced satisfaction levels. The ERT experience varied significantly by country, as evidenced by satisfaction (p = 0.05), delivery (p = 0.001), teacher-student interaction (p = 0.04), and willingness to use ERT in the future (p = 0.04). However, concerns were raised about the depth of content, the transition to online delivery, teacher-student interaction, and the technology gap. Conclusions Our findings can help advance nursing education. Nevertheless, collaborative efforts from all stakeholders are essential to address current challenges, achieve digital equity, and develop a standardized curriculum for nursing education.

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

Introduction: During the COVID-19 pandemic, healthcare providers have been in great fear due to the high risk of contracting COVID-19 infection at any time. This study aimed to determine the mediating role of resilience on the relationship between fear of COVID-19 and burnout in primary care healthcare providers in Malaysia. Methods: This was an online cross-sectional study involving 1280 healthcare providers aged 18 years and older from 30 government primary care clinics in Malaysia. We used the COVID-19 Fear Scale, the Copenhagen Burnout Inventory Scale, and the Short Brief Resilience Scale to collect data from the respondents. Smart-PLS was used to perform mediation analysis. Results: The mean age of the respondents was 36 years old and mean duration of working experience was 11 years. The majority of the respondents were female (82.4%) and Malays (82.3%). The study population consisted of nurses (47.4%), doctors (26%), medical assistants (11.9), healthcare assistant (7.1%), medical laboratory technicians (6.4%) and drivers(1.3).The results show that fear of COVID-19 positively predicts burnout. According to the results, resilience mediates the relationship between fear of COVID-19 and all the three burnout domains, namely personal burnout (β=0.175,p<0.001), work-related burnout (β=0.175,p<0.001) and client-related burnout (β=0.172,p<0.001). Additionally, resilience reduces the impact of COVID-19 fear on the three domains of burnout. Conclusion: Our study has reported a mediating effect of resilience on the relationship between fear of COVID-19 and burnout.

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7 ,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. T o expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

COVID-19/transmission* ; Communicable Disease Control/organization & administration* ; Education, Distance/organization & administration* ; Education, Medical/organization & administration* ; Humans ; Otolaryngology/organization & administration* ; Singapore/epidemiology* ; Telemedicine/organization & administration*

INTRODUCTION: The COVID-19 pandemic has affected the world for more than a year, with multiple waves of infections resulting in morbidity, mortality and disruption to the economy and society. Response measures employed to control it have generally been effective but are unlikely to be sustainable over the long term. METHODS: We examined the evidence for a vaccine-driven COVID-19 exit strategy including academic papers, governmental reports and epidemiological data, and discuss the shift from the current pandemic footing to an endemic approach similar to influenza and other respiratory infectious diseases. RESULTS: A desired endemic state is characterised by a baseline prevalence of infections with a generally mild disease profile that can be sustainably managed by the healthcare system, together with the resumption of near normalcy in human activities. Such an endemic state is attainable for COVID-19 given the promising data around vaccine efficacy, although uncertainty remains around vaccine immunity escape in emergent variants of concern. Maintenance of non-pharmaceutical interventions remains crucial until high vaccination coverage is attained to avoid runaway outbreaks. It may also be worthwhile to de-escalate measures in phases, before standing down most measures for an endemic state. If a variant that substantially evades immunity emerges, it will need to be managed akin to a new disease threat, with pandemic preparedness and response plans. CONCLUSION An endemic state for COVID-19, characterised by sustainable disease control measures, is likely attainable through vaccination.
COVID-19 ; Disease Outbreaks/prevention & control* ; Humans ; Influenza, Human/prevention & control* ; Pandemics/prevention & control* ; SARS-CoV-2

Purpose: The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. Materials and Methods: Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. Results: The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. Conclusion Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.