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Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+ ; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.
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Fibroblastos Associados a Câncer , Neoplasias Pulmonares , MicroRNAs , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica/patologiaRESUMO
PURPOSE: Dart-thrower's motion (DTM) is a functional wrist movement from maximum radial extension to maximum ulnar flexion. This study defines a reference range of DTM in a healthy population. METHODS: Goniometric measurements were collected from both wrists of 200 healthy volunteers. Mean age was 21.1 years (range, 18-25 years), 126 volunteers (63%) were female, and 177 (89%) were right-handed. Volunteers also reported perceived difficulty of performing DTM. RESULTS: For male subjects, the mean arc of motion was 126° (range, 83°-166°) for dominant and 114° (range, 62°-148°) for nondominant wrists. For female subjects, the mean values were 129° (range, 79°-170°) and 126° (range, 70°-167°), respectively. On multiple regression analysis, female subjects had a significantly increased range of dominant and nondominant arc of motion compared with males. Older subjects had significantly increased dominant but reduced nondominant arc of motion. High inter- and intrarater reliability was observed for goniometric measurement of DTM (intraclass correlation coefficients, 0.93-0.98). CONCLUSIONS: This study quantified a reference range of DTM in normal individuals. CLINICAL RELEVANCE: This study provides a reference range for DTM in a young adult population, which may aid clinical comparison of measurements of wrist movement and evaluation of conditions and treatments that impact DTM.
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Articulação do Punho , Punho , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Amplitude de Movimento Articular , Valores de Referência , Reprodutibilidade dos Testes , Articulação do Punho/diagnóstico por imagem , Adulto JovemRESUMO
AIMS AND OBJECTIVES: The aim of this study was to assess a community-women health ambassadors programme and report the areas that were successful and those that required improvement. The objectives were to assess the feasibility, effectiveness, implementation and sustainability of the programme. BACKGROUND: Health promotion for the prevention of chronic diseases has always been the top priority in the health sector. To ensure that the relevant health messages are well received in local communities, a health promotion programme must be accessible, acceptable and culturally relevant. DESIGN: We conducted and evaluated a women health ambassador programme based on the lay health advisor model for health promotion in Hong Kong during November 2014 to February 2015. Health needs and the subsequent focus of the programme were determined by underprivileged Chinese women. METHODS: University health educators from different disciplines trained the women (N = 80) to be health ambassadors through mini-lectures and training workshops. The trained women raised awareness about the importance of health within their families and social networks. The programme was evaluated through attendance rates, questionnaires and quizzes, changes in knowledge and behaviour, as well as qualitative discussion. RESULTS: While the majority of participants found the programme valuable and useful, retention rates were unideal. A statistically significant improvement was found in eating habits, but no significant change was identified for other knowledge and behaviour assessments. CONCLUSIONS: The programme empowered underprivileged women to reflect on the importance of health, take responsibility for their own health and actively promote health to their families and personal communities. RELEVANCE TO CLINICAL PRACTICE: Our study supports that health promotion programmes based on the lay health advisor model are effective and encourage large-scale programmes of this nature. Our results also support that future health promotion efforts should deliver brief, clear and simple content as opposed to intricate information.
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Promoção da Saúde/métodos , Avaliação de Programas e Projetos de Saúde , Saúde Pública/normas , Saúde da Mulher , Adulto , Doença Crônica/prevenção & controle , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hong Kong , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Inquéritos e QuestionáriosRESUMO
PURPOSE: The aim of this study was to report translation and transcultural adaptation of the 15-item Dispositional Resilience Scale in traditional Chinese (C-DRS-15) and evaluate its psychometric properties. METHODS: The DRS is a self-report instrument that measures psychological hardiness. We followed an international standard of cross-cultural translation and validation of patient-reported outcome measures to create the Chinese version. Then, the translated C-DRS-15 was validated on 542 Chinese women from a population-based sample in Hong Kong. RESULTS: The internal consistency and criterion-related validity were investigated. Exploratory and confirmatory factor analysis revealed that the C-DRS-15 was supported by a modified three-factor structure in our Chinese sample (RMSEA = .06, CFI = .94, TLI = .92, and SRMR = .06). The reliability (Cronbach's α coefficient = .78) and validity were satisfactory. Total resilience score was negatively correlated with depression (p < .001), with non-depressed women scoring higher on the C-DRS-15. CONCLUSIONS: The C-DRS-15 was demonstrated to be a reliable and valid measurement to assess hardiness in Chinese women.
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Psicometria , Resiliência Psicológica , Inquéritos e Questionários/normas , Adulto , Povo Asiático , Comparação Transcultural , Depressão , Análise Fatorial , Feminino , Hong Kong , Humanos , Transtornos Mentais , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Resiliência Psicológica/classificação , Adulto JovemRESUMO
OBJECTIVE: This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses. METHODS: The number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients' characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded. RESULTS: In total, 1110 referrals from the pre-calculator period were compared with 1559 from the post-calculator period. Patient characteristics were comparable for both cohorts. More patients were referred on the cancer pathway in the post-calculator cohort (pre-calculator patients 51.1 per cent vs post-calculator 64.0 per cent). The cancer diagnosis rate increased from 2.7 per cent in the pre-calculator cohort to 3.3 per cent in the post-calculator cohort. A lower rate of cancer diagnosis in the non-cancer pathway occurred in the cohort managed using the Head and Neck Cancer Risk Calculator version 2 (10 per cent vs 23 per cent, p = 0.10). CONCLUSION: Head and Neck Cancer Risk Calculator version 2 demonstrated high sensitivity in cancer diagnosis. Further studies are required to improve the predictive strength of the calculator.
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Significance: Statistical inference in functional neuroimaging is complicated by the multiple testing problem and spatial autocorrelation. Common methods in functional magnetic resonance imaging to control the familywise error rate (FWER) include random field theory (RFT) and permutation testing. The ability of these methods to control the FWER in optical neuroimaging has not been evaluated. Aim: We attempt to control the FWER in optical intrinsic signal imaging resting-state functional connectivity using both RFT and permutation inference at a nominal value of 0.05. The FWER was derived using a mass empirical analysis of real data in which the null is known to be true. Approach: Data from normal mice were repeatedly divided into two groups, and differences between functional connectivity maps were calculated with pixel-wise t -tests. As the null hypothesis was always true, all positives were false positives. Results: Gaussian RFT resulted in a higher than expected FWER with either cluster-based (0.15) or pixel-based (0.62) methods. t -distribution RFT could achieve FWERs of 0.05 (cluster-based or pixel-based). Permutation inference always controlled the FWER. Conclusions: RFT can lead to highly inflated FWERs. Although t -distribution RFT can be accurate, it is sensitive to statistical assumptions. Permutation inference is robust to statistical errors and accurately controls the FWER.
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In this study, we studied historical case notes to examine nomenclature of congenital upper limb anomalies and explore the changes in terminologies over time. Original diagnoses were reclassified according to previously published classifications and the most recent Oberg, Manske and Tonkin system. Two hundred and thirty-eight case notes were obtained from the period 1961-1991. Hand plate malformations where the diagnosis was obvious or traumatic defects, were excluded. Eighty-six cases (106 extremities) were finally included where an ambiguous diagnosis, such as 'congenital absence' was initially given. None of the re-classifications matched the original diagnoses except for cleft hand and radial dysplasia (n = 31). Eighteen phocomelia-type limbs were re-classifiable when seen as a continuum of longitudinal deficiency, but not as an intercalary deficit. This study provided further insights into the evolving nature of nomenclature in congenital upper limb anomalies, especially for the condition of phocomelia.Level of evidence: IV.
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Ectromelia , Deformidades Congênitas da Mão , Deformidades Congênitas das Extremidades Superiores , Humanos , Síndrome , Extremidade SuperiorRESUMO
Significance: Resting-state functional connectivity imaging in mice with optical intrinsic signal (OIS) imaging could provide a powerful translational tool for developing imaging biomarkers in preclinical disease models. However, statistical interpretation of correlation coefficients is hampered by autocorrelations in the data. Aim: We sought to better understand temporal and spatial autocorrelations in optical resting-state data. We then adapted statistical methods from functional magnetic resonance imaging to improve statistical inference. Approach: Resting-state data were obtained from mice using a custom-built OSI system. The autocorrelation time was calculated at each pixel, and z scores for correlation coefficients were calculated using Fisher transforms and variance derived from either Bartlett's method or xDF. The significance of each correlation coefficient was determined through control of the false discovery rate (FDR). Results: Autocorrelation was generally even across the cortex and parcellation reduced variance. Correcting variance with Bartlett's method resulted in a uniform reduction in z scores, with xDF preserving high z scores for highly correlated data. Control of the FDR resulted in reasonable thresholding of the correlation coefficient matrices. The use of Bartlett's method compared with xDF results in more conservative thresholding and fewer false positives under null hypothesis conditions. Conclusions: We developed streamlined methods for control of autocorrelation in OIS functional connectivity data in mice, and Bartlett's method is a reasonable compromise and simplification that allows for accurate autocorrelation correction. These results improve the rigor and reproducibility of functional neuroimaging in mice.
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Introduction: Debriefing plays a vital role in effective simulation-based learning by providing feedback to students to foster their development of critical thinking in the learning. Objectives: We evaluated the effects of rubric-based debriefing on students' critical thinking, level of confidence in performing tasks and communication. Method: This is a quasi-experimental study. Final year nursing undergraduates (n=204) of a local university participated in the study. In the intervention group, students performed two 20 min simulation sessions individually with simulated patients followed by a 15 min individual rubric-based debriefing between the two sessions and had a 5 min of that at the end. In the control group, students performed the same simulation sessions followed by a 20 min individual rubric-based debriefing at the end. The primary outcome was comparing the critical thinking of students between two groups, which was assessed by The Northeastern Illinois University Critical Thinking Rubric. The qualitative data were collected by an open-ended question. Results: Based on generalised estimating equation models, the intervention effect over time was found to be statistically significant (ß=2.06, 95% CI 1.04 to 3.08) in enhancing students' critical thinking. No statistically significant differences were reported in the self-perceived confidence levels between the intervention group and control group. Qualitative data reflected positive feedback from students on simulation activities. Conclusions: This is the first study to provide evidence that a rubric-based debriefing enhances students' critical thinking in simulation learning.
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Relatively little research has assessed the exposure-response relationship of childhood adversities on engaging in risky sexual behaviors. Also, no previous research has examined the interrelationship among childhood adversities, adult anxiety and depressive symptoms, and risky sexual behaviors. This study aimed to investigate their interrelationships. We used data from a multisite survey of emerging adults aged 18 to 29 studying at four universities in Hong Kong between September and December 2015. Structural equation modeling (SEM) was used to examine the pathways from childhood adversities to risky sexual behaviors. Participants who had higher childhood adversity scores reported more severe adult anxiety symptoms (ß = 0.20, p = 0.002); and adult anxiety symptoms were associated with significantly more risky sexual behaviors (ß = 0.46, p < 0.0001). The model with adult anxiety symptoms as the mediator between childhood adversities and risky sexual behaviors showed good fit (root mean square error of approximation [RMSEA] = 0.04, comparative fit index [CFI] = 0.96, Tucker-Lewis index [TLI] = 0.94 and standardized root mean square residual [SRMSR] = 0.04). However, adult depressive symptoms failed to mediate between childhood adversities and risky sexual behaviors. This study demonstrates the link between childhood adversities and risky sexual behaviors via adult anxiety but not adult depressive symptoms. It is essential to reduce anxious symptoms in dealing with emerging adults who have risky sexual behaviors to prevent sexually transmitted infections (STIs) and unintended pregnancy.