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Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates., Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates., Design, Setting, and Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled., Main Outcomes and Measures: For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population., Results: The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes., Conclusions and Relevance: This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.

Background: Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive., Methods: Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE., Results: We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters., Conclusion: Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells., (© 2024. The Author(s).)

Introduction: Adolescents presenting with medically unexplained symptoms (MUS) in non-mental healthcare settings, particularly Emergency Departments (EDs), pose diagnostic challenges necessitating a comprehensive bio-psycho-social approach. Amid the youth mental health crisis, recognising psychological distress is imperative. This study delved into physicians' perceptions and diagnostic tendencies regarding such cases, exploring the potential overshadowing of psychosomatic presentations by medicalized diagnoses in EDs., Methods: Our study involved 74 physicians, representing 82% of eligible respondents in the Paediatric Emergency Medicine Department, and was conducted using an online questionnaire examining perceptions of case scenarios with psychosomatic presentations., Results: Results disclosed a prevalent inclination toward medical diagnoses, with less than 10% of physicians considering psychosomatic conditions in specific scenarios. Interestingly, psychosomatic diagnoses were more probable for symptoms like headaches, shortness of breath, and chest pain. The study uncovered a possible bias among physicians towards medical diagnoses in EDs for adolescents with MUS, possibly stemming from physicians' focus on physical care, diagnostic uncertainties, cognitive biases, and concerns about stigmatisation., Conclusion: Adolescents with MUS seeking assistance in non-mental health settings may encounter delayed mental health diagnoses and interventions. Psychosomatic symptoms could signify stressors or underlying mental health disorders. Recognising psychosocial distress early on is crucial for optimal mental health outcomes. Consequently, the study advocates for a paradigm shift towards a holistic bio-psychosocial approach in both medical education and practice., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Objectives: To evaluate early- and long-term outcomes of the surgical treatment for coarctation of the aorta based on a new classification system., Methods: A retrospective clinical review of 111 patients with coarctation of the aorta who underwent surgery (March 2011 to August 2020) was performed. We categorised coarctation of the aorta into type I, with all three head vessels tightly packed; type II, with the left subclavian artery separated from the two other head vessels; and type III, with all three head vessels separated from one another. Each type included subtype a, with a short isthmic portion, and subtype b, with a long isthmic portion., Results: The median patient age and weight at operation were 8 (range, 1-1490) days and 3.2 (range, 1.9-18.5) kg, respectively. Extended end-to-end anastomosis was performed via sternotomy in 54, via thoracotomy in 12, end-to-side anastomosis in 31, autologous main pulmonary artery patch augmentation in 12, and modified end-to-end anastomosis combined with subclavian artery flap aortoplasty in two patients. There was one (0.9%) case of early mortality and 12 (10.8%) cases of post-operative complications. Two (1.8%) late deaths occurred during follow-up. Five (4.5%) patients underwent balloon dilatation and three (2.7%) underwent reoperation for restenosis of coarctation of the aorta. All patients with type Ia (21 patients, 18.9%) underwent extended end-to-end anastomosis via sternotomy or thoracotomy., Conclusions: According to the early and late outcomes observed in this study, surgical treatment of coarctation of the aorta using the new classification system could be safe and low risk.

Introduction: We investigated the knowledge, attitudes and practice (KAP) towards coronavirus disease 2019 (COVID-19) and its related preventive measures in Singaporeans aged ≥60 years., Methods: This was a population-based, cross-sectional, mixed-methods study (13 May 2020-9 June 2020) of participants aged ≥ 60 years. Self-reported KAP about ten symptoms and six government-endorsed preventive measures related to COVID-19 were evaluated. Multivariable regression models were used to identify sociodemographic and health-related factors associated with KAP in our sample. Associations between knowledge/attitude scores and practice categories were determined using logistic regression. Seventy-eight participants were interviewed qualitatively about the practice of additional preventive measures and data were analysed thematically., Results: Mean awareness score of COVID-19 symptoms was 7.2/10. The most known symptom was fever (93.0%) and the least known was diarrhoea (33.5%). Most participants knew all six preventive measures (90.4%), perceived them as effective (78.7%) and practised 'wear a mask' (97.2%). Indians, Malays and participants living in smaller housing had poorer mean scores for knowledge of COVID-19 symptoms. Older participants had poorer attitudes towards preventive measures. Compared to Chinese, Indians had lower odds of practising three out of six recommendations. A one-point increase in score for knowledge and attitudes regarding preventive measures resulted in higher odds of always practising three of six and two of six measures, respectively. Qualitative interviews revealed use of other preventive measures, for example, maintaining a healthy lifestyle., Conclusions: Elderly Singaporeans displayed high levels of KAP about COVID-19 and its related preventive measures, with a positive association between levels of knowledge/attitude and practice. However, important ethnic and socioeconomic disparities were evident, indicating that key vulnerabilities remain, which require immediate attention., Competing Interests: None

One's working memory process is a fundamental cognitive activity which often serves as an indicator of brain disease and cognitive impairment. In this research, the approach to evaluate working memory ability by means of electroencephalography (EEG) analysis was proposed. The result shows that the EEG signals of subjects share some characteristics when performing working memory tasks. Through correlation analysis, a working memory model describes the changes in EEG signals within alpha, beta and gamma waves, which shows an inverse tendency compared to Zen meditation. The working memory ability of subjects can be predicted using multi-linear support vector regression (SVR) with fuzzy C-mean (FCM) clustering and knowledge-based fuzzy support vector regression (FSVR), which reaches the mean square error of 0.6 in our collected data. The latter, designed based on the working memory model, achieves the best performance. The research provides the insight of the working memory process from the EEG aspect to become an example of cognitive function analysis and prediction.

Background: Chronic Obstructive lung diseases (COPD) are complex conditions influenced by various environmental, lifestyle, and genetic factors. Ambient air pollution has been identified as a potential risk factor, causing 4.2 million deaths worldwide in 2016, accounting for 25% of all COPD-related deaths and 26% of all respiratory infection-related deaths. This study aims to evaluate the associations among chronic lung diseases, air pollution, and meteorological factors., Methods: This cross-sectional study obtained data from the Taiwan Biobank and Taiwan Air Quality Monitoring Database. We defined obstructive lung disease as patients with FEV1/FVC < 70%. Descriptive analysis between spirometry groups was performed using one-way ANOVA and the chi-square or Fisher's exact test. A generalized additive model (GAM) was used to evaluate the relationship between SO 2 and PM 2.5 /PM 10 through equations and splines fitting., Results: A total of 2,635 participants were enrolled. Regarding environmental factors, higher temperature, higher relative humidity, and lower rainfall were risk factors for obstructive lung disease. SO 2 was positively correlated with PM 10 and PM 2.5 , with correlation coefficients of 0.53 ( p < 0.0001) and 0.52 (p < 0.0001), respectively. Additionally, SO 2 modified the relative risk of obstructive impairment for both PM 10 [ β coefficient ( β ) = 0.01, p = 0.0052] and PM 2.5 ( β = 0.01, p = 0.0155). Further analysis per standard deviation (per SD) increase revealed that SO 2 also modified the relationship for both PM 10 ( β = 0.11, p = 0.0052) and PM 2.5 ( β = 0.09, p = 0.0155). Our GAM analysis showed a quadratic pattern for SO 2 (per SD) and PM 10 (per SD) in model 1, and a quadratic pattern for SO 2 (per SD) in model 2. Moreover, our findings confirmed synergistic effects among temperature, SO 2 and PM 2.5 /PM 10 , as demonstrated by the significant associations of bivariate (SO 2 vs. PM 10 , SO 2 vs. PM 2.5 ) thin-plate smoothing splines in models 1 and 2 with obstructive impairment ( p < 0.0001)., Conclusion: Our study showed high temperature, humidity, and low rainfall increased the risk of obstructive lung disease. Synergistic effects were observed among temperature, SO 2 , and PM 2.5 /PM 10 . The impact of air pollutants on obstructive lung disease should consider these interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Chen, Wang, Tu, Chen, Hu, Li, Wu, Hung and Kuo.)

Background: Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated., Methods: Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan-Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry., Results: Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin-a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes-reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin., Conclusions: The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC., (© 2023. The Author(s).)

Competing Interests: There are no conflicts of interest.

Background: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms., Methods: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone., Discussion: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety., Trial Registration: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018., (© 2022. The Author(s).)

Lung cancer is one of the leading causes of cancer mortality worldwide. As it is often first diagnosed only when cancer metastasis has already occurred, the development of effective biomarkers for the risk prediction of cancer metastasis, followed by stringent monitoring and the early treatment of high-risk patients, is essential for improving patient survival. Cancer cells exhibit alterations in metabolic pathways that enable them to maintain rapid growth and proliferation, which are quite different from the metabolic pathways of normal cells. Fumarate hydratase (FH, fumarase) is a well-known tricarboxylic acid cycle enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. The current study sought to investigate the relationship between FH expression levels and the outcome of patients with lung cancer. FH was knocked down in lung cancer cells using shRNA or overexpressed using a vector, and the effect on migration ability was assessed. Furthermore, the role of AMP-activated protein kinase (AMPK) phosphorylation and disabled homolog 2 in the underlying mechanism was investigated using an AMPK inhibitor approach. The results showed that in lung cancer tissues, low FH expression was associated with lymph node metastasis, tumor histology and recurrence. In addition, patients with low FH expression exhibited a poor overall survival in comparison with patients having high FH expression. When FH was overexpressed in lung cancer cells, cell migration was reduced with no effect on cell proliferation. Furthermore, the level of phosphorylated (p-)AMPK, an energy sensor molecule, was upregulated when FH was knocked down in lung cancer cells, and the inhibition of p-AMPK led to an increase in the expression of disabled homolog 2, a tumor suppressor protein. These findings suggest that FH may serve as an effective biomarker for predicting the prognosis of lung cancer and as a therapeutic mediator., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Vadhan et al.)

COVID-19 vaccination in healthcare workers (HCW) is essential for improved patient safety and resilience of health systems. Despite growing body of literature on the perceptions of COVID vaccines in HCWs, existing studies tend to focus on reasons for 'refusing' the vaccines, using surveys almost exclusively. To gain a more nuanced understanding, we explored multifactorial influences underpinning a decision on vaccination and suggestions for decision support to improve vaccine uptake among HCWs in the early phase of vaccination rollout. Semi-structured interviews were undertaken with thirty-three HCWs in Singapore. Transcribed data was thematically analyzed. Decisions to accept vaccines were underpinned by a desire to protect patients primarily driven by a sense of professional integrity, collective responsibility to protect others, confidence in health authorities and a desire to return to a pre-pandemic way of life. However, there were prevailing concerns with respect to the vaccines, including long-term benefits, safety and efficacy, that hampered a decision. Inadequate information and social media representation of vaccination appeared to add to negative beliefs, impeding a decision to accept while low perceived susceptibility played a moderate role in the decision to delay or decline vaccination. Participants made valuable suggestions to bolster vaccination. Our findings support an approach to improving vaccine uptake in HCWs that features routine tracking and transparent updates on vaccination status, use of institutional platforms for sharing of experience, assuring contingency management plans and tailored communications to emphasize the duty of care and positive outlook associated with vaccination.

The primary cause of breast cancer mortality is the metastatic invasion of cancerous stem cells (CSC). Cluster of differentiation 44 (CD44) is a well-known CSC marker in various cancers, as well as a key role player in metastasis and relapse of breast cancer. CD44 is a cell-membrane embedded protein, and it interacts with different proteins to regulate cancer cell behavior. Transcription factor forkhead box protein A2 (FOXA2) acts as an important regulator in multiple cancers, including breast cancer. However, the biological significance of CD44-FOXA2 association in breast cancer metastasis remains unclear. Herein, we observed that CD44 expression was higher in metastatic lymph nodes compared to primary tumors using a flow cytometric analysis. CD44 overexpression in breast cancer cell lines significantly promoted cell migration and invasion abilities, whereas the opposite effects occurred upon the knockdown of CD44. The stem cell array analysis revealed that FOXA2 expression was upregulated in CD44 knockdown cells. However, the knockdown of FOXA2 in CD44 knockdown cells reversed the effects on cell migration and invasion. Furthermore, we found that CD44 mediated FOXA2 localization in breast cancer cells through the AKT pathway. Moreover, the immunofluorescence assay demonstrated that AKT inhibitor wortmannin and AKT activator SC79 treatment in breast cancer cells impacted FOXA2 localization. Collectively, this study highlights that CD44 promotes breast cancer metastasis by downregulating nuclear FOXA2.

Background: A successful public health response during the COVID-19 pandemic pivots on the ability of health care workers (HCWs) to work through immense workplace-related physical and psychological pressures., Objective: The aim of current study was to explore support needs of HCWs during the COVID-19 outbreak in Singapore and to identify implications for practice and workplace policies., Methods: A descriptive qualitative approach was adopted in this study. HCWs from a major public health care cluster in Singapore (n = 612) responded to an open-ended question in an online survey. Results were analyzed using content analysis via an inductive approach., Results: Five main themes that borrows from Maslow's Hierarchy of Needs emerged from content analysis, with 17 categories under the themes. The 5 main themes are: physical needs, safety needs, love and belonging needs, esteem needs and self-actualization needs., Conclusions: Findings from this study indicate that there were many unmet needs among HCWs during the COVID-19 pandemic. An overview of various need areas identified in this study may guide future research and development of interventions to mitigate the negative impact of disease outbreaks on HCWs., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy., (© 2022. The Author(s).)

Background: To determine the effectiveness of ethanol (EtOH) washing on porcine pulmonary artery (PA) wall decellularization using sodium dodecyl sulfate (SDS), we compared three different washing methods (phosphate-buffered saline [PBS], pH 9 alkali, and EtOH washing)., Methods: Fresh porcine PA walls were decellularized using 0.5% SDS and 0.5% sodium deoxycholate (SDC). The decellularized tissues were rinsed using three different washing techniques. Histological, biochemical, and mechanical analyses were conducted. Implantation into the subcutaneous tissue of rats and patch implantation into the carotid artery of dogs were performed as preliminary in vivo studies., Results: The decellularization protocol based on SDS and SDC effectively removed the cells. The major extracellular matrix (ECM) structures (collagen, elastic fiber, and glycosaminoglycan) were properly preserved with the 75% EtOH-washing method. Significantly reduced residual SDS content was identified in EtOH-washed tissues compared to that in the other methods. No significant difference in the mechanical strength test was observed between the washing methods, and the EtOH-washing method showed better results in the metabolic activity test compared to the PBS-washing method. In the rat study model, no acute rejection or massive calcification was observed. The in vivo preliminary canine study showed better cell repopulation in the EtOH-washed group., Conclusion: EtOH washing of SDS-based decellularized porcine PA wall can reduce the residual SDS content and preserve ECM structures, especially the elastin content, and could also enhance cell repopulation after re-implantation., (© 2022 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: How well team members work together can be affected by team interactions and creativity. There is no single instrument for measuring both variables in healthcare education settings in Taiwan. The purpose of this study is to develop an instrument to measure team interactions and team creativity for Taiwanese nursing students., Methods: A 34-item team interactions and team creativity self-report instrument was developed for nursing students in Taiwan (TITC-T). Items consisted of statements about how a participant perceived their team members' constructive controversy, helping behaviors, communication, and creativity. Nursing students ( n = 275) were recruited from two campuses of a science and technology university to examine the psychometric properties of the TITC-T. The reliability and psychometric properties were evaluated., Results: The Cronbach's alpha was 0.98. The confirmatory factor analysis resulted in a one-dimensional factor structure that fit well with the model (Comparative Fit Index = 0.995, Tucker Lewis Index = 0.908, Root Mean Square Error of Approximation = 0.098)., Conclusions: The TITC-T is a valid and reliable tool for evaluating team interactions and team creativity for students enrolled in nursing programs in Taiwan.

Objectives: This study examined the prevalence of anxiety, depression, and job burnout among frontline healthcare workers (HCWs) across six Southeast Asian countries (Indonesia, Malaysia, Philippines, Singapore, Thailand, Vietnam) during the COVID-19 pandemic in 2021. We also investigated the associated risk and protective factors., Methods: Frontline HCWs (N = 1381) from the participating countries participated between 4 January and 14 June 2021. The participants completed self-reported surveys on anxiety (GAD-7), depression (PHQ-8), and job burnout (PWLS). Multivariate logistic regressions were performed with anxiety, depression, and job burnout as outcomes and sociodemographic and job characteristics and HCW perceptions as predictors., Results: The average proportion of HCWs reporting moderate anxiety, moderately severe depression, and job burnout across all countries were 10%, 4%, and 20%, respectively. Working longer hours than usual (Odds ratio [OR] = 1.82; 3.51), perceived high job risk (1.98; 2.22), and inadequate personal protective equipment (1.89; 2.11) were associated with increased odds of anxiety and job burnout while working night shifts was associated with increased risk of depression (3.23). Perceived good teamwork was associated with lower odds of anxiety (0.46), depression (0.43), and job burnout (0.39)., Conclusion: Job burnout remains a foremost issue among HCWs. Potential opportunities to improve HCW wellness are discussed.

Virtual reality exposure therapy (VRET) has been commonly utilised as an extension of cognitive behavioural therapy (CBT). However, most studies examined its effectiveness among adults, with no study focusing on children with selective mutism (SM). We aimed to examine its feasibility and acceptability among children with SM. Twenty children aged 6-12 with SM diagnosis were recruited and completed six therapist-guided VRET sessions. Parents and clinicians completed measures at pre-VRET, post-VRET, 1-month and 3-month follow-up visits. At post-VRET, parent and child participants completed the acceptability questionnaires. Findings suggested the feasibility of VRET as all participants completed the programme with no attrition. Parents and child participants also reported VRET to be an acceptable and effective treatment for SM. Significant improvement in overall functioning were found at post-treatment and follow-up measures, but there were no significant changes in parent-rated speech frequency and anxiety measures. These support the acceptability of VRET as an adjunct modality (and not substitute) of CBT in SM treatment. Future studies, with more robust experimental designs and larger sample sizes, can be conducted to confirm its efficacy. As technology becomes more sophisticated, tools such as virtual environments can be explored to enhance evidence-based care for children and their families.

Background: Several countries have implemented 'lockdown' measures to curb the spread of the coronavirus disease 2019 (COVID-19)., Aims: To examine the psychological, physical activity (PA), and financial impact of a 2-month COVID-19 lockdown on older adults aged ≥60 years in Singapore, and to identify factors associated with adverse lockdown-related outcomes., Method: We interviewed 496 community-dwelling adults (mean age [standard deviation]: 73.8 [7.6] years; 54.8% female) during the lockdown who had previously participated in a population-based epidemiological study. Validated questionnaires were utilised to assess loneliness and depressive symptoms at both timepoints, while inhouse questionnaires were used to assess PA and financial difficulty during lockdown. Multivariable regression models determined the lockdown-related change in loneliness and depression scores, and the factors associated with adverse outcomes., Results: Loneliness increased significantly during the lockdown period (p < 0.001) while depressive symptoms decreased (p = 0.022). Decreased PA, greater financial problems, male gender, Indian ethnicity, living alone, having a greater body mass index and perceived susceptibility to COVID-19 were all associated with worsening loneliness scores. A total of 36.9% and 19.6% participants reported decreased PA and had financial problems during the lockdown, respectively. Unemployment was associated with decreased PA, while self-employed individuals, cleaners, retail workers and smokers had greater odds of experiencing financial difficulty., Conclusion: Despite a decrease in depressive symptoms, our population of older Asians reported a significant increase in loneliness and decreased PA, with one-fifth experiencing financial problems during lockdown. Our data suggest that more targeted public health efforts are needed to reduce repercussions of future lockdowns., (© 2021 John Wiley & Sons Ltd.)

Esophageal cancer is one of the most common malignancies and leading cause of cancer-associated mortality worldwide. However, the molecular mechanisms underlying esophageal cancer progression and the development of clinical tools for effective diagnosis remain unclear. Resistin, which was originally identified as an adipose tissue-secretory factor, has been associated with obesity-related diseases, including certain types of cancer. Thus, the present study aimed to investigate the expression levels of resistin in tissue and serum specimens from patients with esophageal squamous cell carcinoma (ESCC) to determine the potential biological effects of resistin on ESCC cells. The results demonstrated that both tissue and serum resistin levels were significantly lower in patients with ESCC compared with healthy controls. In addition, resistin expression was positively associated with the body mass index of patients with ESCC. In vitro studies revealed that resistin inhibited the migratory ability of ESCC cells, while having no effect on ESCC cell proliferation. Taken together, these results suggest that resistin may have the potential to be developed into a clinical marker for ESCC. However, further studies are required to investigate resistin receptor expression and determine the potential involvement of resistin-associated biological pathways, which may provide insight for future development of targeted therapies for resistin-mediated ESCC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Hung et al.)

Aim: The long-term stress, anxiety and job burnout experienced by healthcare workers (HCWs) are important to consider as the novel coronavirus disease (COVID-19) pandemic stresses healthcare systems globally. The primary objective was to examine the changes in the proportion of HCWs reporting stress, anxiety, and job burnout over six months during the peak of the pandemic in Singapore. The secondary objective was to examine the extent that objective job characteristics, HCW-perceived job factors, and HCW personal resources were associated with stress, anxiety, and job burnout., Method: A sample of HCWs (doctors, nurses, allied health professionals, administrative and operations staff; N = 2744) was recruited via invitation to participate in an online survey from four tertiary hospitals. Data were gathered between March-August 2020, which included a 2-month lockdown period. HCWs completed monthly web-based self-reported assessments of stress (Perceived Stress Scale-4), anxiety (Generalized Anxiety Disorder-7), and job burnout (Physician Work Life Scale)., Results: The majority of the sample consisted of female HCWs (81%) and nurses (60%). Using random-intercept logistic regression models, elevated perceived stress, anxiety and job burnout were reported by 33%, 13%, and 24% of the overall sample at baseline respectively. The proportion of HCWs reporting stress and job burnout increased by approximately 1·0% and 1·2% respectively per month. Anxiety did not significantly increase. Working long hours was associated with higher odds, while teamwork and feeling appreciated at work were associated with lower odds, of stress, anxiety, and job burnout., Conclusions: Perceived stress and job burnout showed a mild increase over six months, even after exiting the lockdown. Teamwork and feeling appreciated at work were protective and are targets for developing organizational interventions to mitigate expected poor outcomes among frontline HCWs., Competing Interests: The authors have declared that no competing interests exist.

Background: Persistent fifth aortic arch (PFAA) is a rare anomaly often associated with aortic coarctation or interruption, and various surgical techniques for this anomaly have been reported. Herein, we show a case of an infant with PFAA and severe aortic coarctation., Case Presentation: A 41-day-old female infant was admitted for sustained fever. Initially, the patient was diagnosed with bacterial meningitis, and echocardiography showed PFAA with severe aortic coarctation. Because the patient presented progressive oliguria and metabolic acidosis, she was transferred for emergency cardiac surgical intervention. The aortic arch was reconstructed using end-to-side anastomosis between the fifth aortic arch and the descending aorta without any artificial conduit or patching material., Conclusions: PFAA with aortic coarctation can be repaired by various surgical methods. Among them, our surgical approach is easy and effective, has growth potential, and an additional surgery is not needed., (© 2021. The Author(s).)

The aim of this study was to investigate the association between frailty and polypharmacy using three different frailty screening tools. This was a cross-sectional study of people aged ≥65 years. Participants were included and interviewed using questionnaires. Polypharmacy was defined as the daily use of eight or more pills. Frailty was assessed using a screening tool, including (1) the Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index (5-item FRAIL scale), (2) the Cardiovascular Health Phenotypic Classification of Frailty (CHS&#95;PCF) index (Fried's Frailty Phenotype), and (3) the Study of Osteoporotic Fracture (SOF) scale. A total of 205 participants (mean age: 71.1 years; 53.7% female) fulfilled our inclusion criteria. The proportion of patients with polypharmacy was 14.1%. After adjustments were made for comorbidity or potential confounders, polypharmacy was associated with frailty on the 5-item FRAIL scale (adjusted odds ratio [aOR]: 9.12; 95% confidence interval [CI]: 3.6-23.16), CHS&#95;PCF index (aOR: 8.98; 95% CI: 2.51-32.11), and SOF scale (aOR: 6.10; 95% CI: 1.47-25.3). Polypharmacy was associated with frailty using three frailty screening tools. Future research is required to further enhance our understanding of the risk of frailty among older adults.

Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients.

Background: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA., Methods: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient., Results: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients., Conclusions: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA., (© 2021 Wiley Periodicals LLC.)

Backgrounds: The pleating technique is widely used in plication but is difficult to perform with thoracoscopy because of its complex procedure and the limited surgical space. Thus, the invaginating technique was introduced to facilitate thoracoscopic surgery and is now widely used in video-assisted thoracoscopic surgery (VATS) plication. However, the usefulness of the invaginating technique in children has not been established because of the lack of data on long-term outcomes after surgery using the technique., Methods: From March 2007 to December 2017, 21 patients who were surgically treated for congenital diaphragmatic eventration and phrenic nerve palsy after congenital cardiac surgery were divided into 2 groups according to the surgical method used (pleating technique: 10 patients, invaginating technique: 11 patients). We evaluated the patients for postoperative outcomes and recurrence of diaphragmatic eventration over 5 years. Postoperative recurrence of diaphragmatic eventration was confirmed by calculating the ratio of the eventration level between the eventrated and normal diaphragms., Results: In the 21 patients who underwent diaphragmatic plication, the pleating and invaginating techniques were used in 10 and 11 patients, respectively. The mean follow-up duration was 63.4 ± 48.4 months (pleating group [P] vs invaginating group [I]: 89.1 ± 52.4 vs 40.1 ± 30.8 months, p = 0.022). The mean eventration rates in the 21 patients was 26.7% ± 9.1% (P vs I: 26.6% ± 6.1% vs 26.9% ± 11.3%, p = 0.945) before operation and -2.1% ± 7.3% (-2.8% ± 7.5% vs -1.5% ± 7.4%, p = 0.695) in the immediate postoperative period. From the first to the fifth postoperative year, no recurrence of diaphragmatic eventration was found in any of the groups during the follow-up., Conclusions: The invaginating technique was easier to perform but showed a similar long-term result as compared with the pleating technique in terms of the growth and development of the chest cavity in the pediatric patients in this study. Thus, we recommend that the invaginating technique be applied in VATS plication for children as an alternative to the pleating technique., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.

Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent-tumor-associated macrophages-and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.

We developed a modified Senning procedure in the double-switch operation for the patients with congenitally corrected transposition of the great arteries (ccTGA). In our technique, the right atrial (RA) free wall is not used as a baffle for draining systemic venous blood to the left atrium. Instead, a patch material is used for the baffling. A wide communication between the pulmonary venous chamber and RA is created by making the triangular double door with the RA-free wall, and the window is closed with in situ pericardial flap. We have successfully adopted this technique in our recent two consecutive ccTGA patients., (© 2020 Wiley Periodicals LLC.)

Early mitotic inhibitor 2 (EMI2, gene symbol FBXO43), an APC/C inhibitor regulated by Plx1, is essential for cytostatic factor (CSF) activity. It belongs to subclass FBXO of the F-box proteins family. The aim of this study is to examine the clinicopathological significance of EMI2 in breast cancer. In this study, immunohistochemistry analysis was used to evaluate EMI2 expression in breast cancer tissues and then the association between EMI2 expression and clinicopathological factors was examined. Correlation of EMI2 with patient survival was analyzed by Kaplan-Meier survival curves. Among 192 patients analyzed, 105 (54.7%) had high expression of EMI2, and this was significantly associated with shortened disease free survival and overall survival in breast cancer patients. EMI2 expression was significantly associated with tumor grade (P = .006), tumor size (P < .001), and lymph node metastasis (P = .008). However, there was no significant correlation between EMI2 status and other biomarkers including ER, PR and Her2 status. Our results revealed that elevated EMI2 expression is a risk factor (hazard ratio = 3.93) for breast cancer and overexpression of EMI2 in breast cancer predicts higher risk of metastasis and worse survival. Therefore, EMI2 may be a potential therapeutic target for breast cancer., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)