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The signal transducer and activator of transcription 3 (STAT3) has been established as a crucial drug target in the development of antitumor agents. In this study, a series of 21 derivatives of the STAT3 inhibitor napabucasin were designed and synthesized. Through preliminary screening against tumor cell lines, SZ6 emerged as the most potent compound with half maximal inhibitory concentration (IC50) values of 46.3 nM, 66.4 nM, and 53.8 nM against HCT116, HepG2, and Hela cells respectively. Furthermore, SZ6 effectively suppressed tumor invasion and migration in HCT116 cell assays by inducing S-phase arrest and apoptosis through inhibition of Protein Kinase B (PKB/AKT) activity and induction of reactive oxygen species (ROS). The mechanism underlying SZ6's action involves inhibition of STAT3 phosphorylation, which was confirmed by western blotting analysis. Additionally, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) demonstrated direct binding between SZ6 and STAT3. Notably, in vivo studies revealed that SZ6 significantly inhibited tumor growth without any observed organ toxicity. Collectively, these findings identify SZ6 as a promising STAT3 inhibitor for colorectal cancer treatment.
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Antineoplásicos , Apoptosis , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Factor de Transcripción STAT3 , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Animales , Tiazoles/farmacología , Tiazoles/química , Tiazoles/síntesis química , Ratones , Naftoquinonas/farmacología , Naftoquinonas/síntesis química , Naftoquinonas/química , Ratones Desnudos , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , BenzofuranosRESUMEN
BACKGROUND: Virtual reality-reminiscence therapy (VR-RT) has increasingly been applied to older adults to improve psychological well-being and cognition. OBJECTIVE: This review aims to identify (1) the design characteristics of conducting a VR-RT and (2) the effects of VR-RT on the user experience, cognitive outcomes and psychological well-being. DESIGN: Systematic review. METHODS: Eligible studies were sourced across nine electronic databases, trial registries, grey literature and hand-searching of the reference list. A narrative synthesis was conducted. Twenty-two studies were included, and most were appraised as high quality. Most of the VR-RTs were highly immersive and personalised, with participants having the autonomy of control. VR-RT has the potential to improve anxiety and depression, and cognitive outcomes for older adults. Overall, VR-RT was reported to be an enjoyable experience for older adults. CONCLUSIONS: VR-RT is a promising innovation that can improve older adults' psychological well-being and cognition without significant side effects, including cybersickness and with the potential for scalability across various settings. More randomised controlled studies are needed to evaluate the effectiveness of VR-RT and its features and treatment dosage. These studies could also examine the effectiveness of VR-RT as an intervention to promote independence in activities of daily living and physical rehabilitation. RELEVANCE TO CLINICAL PRACTICE: VR-RT is a promising intervention for older adults in community settings to enhance psychological well-being and cognition. VR's versatility enables personalised experiences within dynamic virtual environments, possibly enhancing engagement and therapeutic outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.
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BACKGROUND: Clinical practicums are a core component of baccalaureate nursing education. Following the coronavirus pandemic, there have been extensive changes in the workforce environment that may potentially affect nursing students' experience and readiness for clinical practicums. METHODS: A qualitative study was conducted to explore final-year nursing students' experiences and readiness for their final clinical practicum before becoming a registered nurse. A purposive sample of 24 final-year baccalaureate nursing students was included in this study. Individual semi-structured interviews were conducted face-to-face via Zoom. The data was analysed using an inductive thematic analysis approach. RESULTS: Three themes depicting students' experiences and clinical readiness were elucidated. The themes included: (1) Experiencing multiple concerns, (2) requiring a network of support, and (3) easing the transition to professional practice. Students considered the final clinical practicum as challenging and demanding which evoked numerous concerns. CONCLUSIONS: Considering the stress that final-year nursing students experience, it will be important to devise strategies ranging from personal, relational, and environmental protective factors to enable their successful transition and completion of clinical practice.
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Bioelectrochemical sensors for environment monitoring have the potential to provide facility operators with real-time data, allowing for better and more timely decision-making regarding water and wastewater treatment. To assess the robustness and sensitivity of the Sentry™ biosensor in local conditions, it was tested in Malaysia using domestically available wastewater. The study objectives included (1) enrich the biosensor locally, (2) operate and test the biosensor with local domestic wastewater, and (3) determine the biosensor's responsiveness to model pollutants through pollutant spike and immersion test as well as response to absence of wastewater. Lab-scale operation shows the biosensor was successfully enriched with (1) local University Kebangsaan Malaysia's, microbial community strain collection and (2) local municipal wastewater microflora, operated for more than 50 days with a stable yet responsive carbon consumption rate (CCR) signal. Meanwhile, two independent biosensors were also enriched and operated in Indah Water Research Centre's crude sewage holding tank, showing a stable response to the wastewater. Next, a pilot scale setup was constructed to test the enriched biosensors for the spiked-pollutant test. The biosensors showed a proportional CCR response (pollutant presence detected) towards several organic compounds in the sewage, including ethanol, chicken blood, and dilution of tested sewage but less to curry powder, methanol, and isopropanol. Conversely, there was no significant response (pollutant presence not detected) towards hexane, Congo red, engine oil, and paint, which may be due to their non-biodegradability and/or insoluble nature. Additionally, the biosensors were exposed to air for 6 h to assess their robustness towards aerobic shock with a positive result. Overall, the study suggested that the biosensor could be a powerful monitoring tool, given its responsiveness towards organic compounds in sewage under normal conditions.
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Contaminantes Ambientales , Aguas Residuales , Humanos , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos , Malasia , Monitoreo del Ambiente , AguaRESUMEN
Tanning and other leather processing methods utilize a large amount of freshwater, dyes, chemicals, and salts and produce toxic waste, raising questions regarding their environmental sensitivity and eco-friendly nature. Total suspended solids, total dissolved solids, chemical oxygen demand, and ions such as chromium, sulfate, and chloride turn tannery wastewater exceedingly toxic for any living species. Therefore, it is imperative to treat tannery effluent, and existing plants must be examined and upgraded to keep up with recent technological developments. Different conventional techniques to treat tannery wastewater have been reported based on their pollutant removal efficiencies, advantages, and disadvantages. Research on photo-assisted catalyst-enhanced deterioration has inferred that both homogeneous and heterogeneous catalysis can be established as green initiatives, the latter being more efficient at degrading organic pollutants. However, the scientific community experiences significant problems developing a feasible treatment technique owing to the long degradation times and low removal efficiency. Hence, there is a chance for an improved solution to the problem of treating tannery wastewater through the development of a hybrid technology that uses flocculation as the primary treatment, a unique integrated photo-catalyst in a precision-designed reactor as the secondary method, and finally, membrane-based tertiary treatment to recover the spent catalyst and reclaimable water. This review gives an understanding of the progressive advancement of a cutting-edge membrane-based system for the management of tanning industrial waste effluents towards the reclamation of clean water. Adaptable routes toward sludge disposal and the reviews on techno-economic assessments have been shown in detail, strengthening the scale-up confidence for implementing such innovative hybrid systems.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Aguas Residuales , Curtiembre , Agua , Residuos Industriales/análisis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisisRESUMEN
The use of chitosan as a flocculant has become a topic of interest over the years due to its positively charged polymer and biodegradable and non-toxic properties. However, most studies only focus on microalgae and wastewater treatment. This study provides crucial insight into the potential of using chitosan as an organic flocculant to harvest lipids and docosahexaenoic acid (DHA-rich Aurantiochytrium sp. SW1 cells by examining the correlation of flocculation parameters (chitosan concentration, molecular weight, medium pH, culture age, and cell density) toward the flocculation efficiency and zeta potential of the cells. A strong correlation between the pH and harvesting efficiency was observed as the pH increased from 3, with the optimal flocculation efficiency of >95% achieved at a chitosan concentration of 0.5 g/L at pH 6 where the zeta potential was almost zero (3.26 mV). The culture age and chitosan molecular weight have no effect on the flocculation efficiency but increasing the cell density decreases the flocculation efficiency. This is the first study to reveal the potential of chitosan to be used as a harvesting alternative for thraustochytrid cells.
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Quitosano , Microalgas , Quitosano/farmacología , Quitosano/química , Floculación , Biomasa , PolímerosRESUMEN
BACKGROUND: Aging degrades the balance and locomotion ability due to frailty and pathological conditions. This demands balance rehabilitation and assistive technologies that help the affected population to regain mobility, independence, and improve their quality of life. While many overground gait rehabilitation and assistive robots exist in the market, none are designed to be used at home or in community settings. METHODS: A device named Mobile Robotic Balance Assistant (MRBA) is developed to address this problem. MRBA is a hybrid of a gait assistive robot and a powered wheelchair. When the user is walking around performing activities of daily living, the robot follows the person and provides support at the pelvic area in case of loss of balance. It can also be transformed into a wheelchair if the user wants to sit down or commute. To achieve instability detection, sensory data from the robot are compared with a predefined threshold; a fall is identified if the value exceeds the threshold. The experiments involve both healthy young subjects and an individual with spinal cord injury (SCI). Spatial Parametric Mapping is used to assess the effect of the robot on lower limb joint kinematics during walking. The instability detection algorithm is evaluated by calculating the sensitivity and specificity in identifying normal walking and simulated falls. RESULTS: When walking with MRBA, the healthy subjects have a lower speed, smaller step length and longer step time. The SCI subject experiences similar changes as well as a decrease in step width that indicates better stability. Both groups of subjects have reduced joint range of motion. By comparing the force sensor measurement with a calibrated threshold, the instability detection algorithm can identify more than 93% of self-induced falls with a false alarm rate of 0%. CONCLUSIONS: While there is still room for improvement in the robot compliance and the instability identification, the study demonstrates the first step in bringing gait assistive technologies into homes. We hope that the robot can encourage the balance-impaired population to engage in more activities of daily living to improve their quality of life. Future research includes recruiting more subjects with balance difficulty to further refine the device functionalities.
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Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Actividades Cotidianas , Calidad de Vida , MarchaRESUMEN
AIM: The aim of the study was to identify and synthesize the contents and the psychometric properties of the existing instruments measuring home-based care (HBC) nurses' competencies. DESIGN: A hybrid systematic narrative review was performed. REVIEW METHODS: The eligible studies were reviewed to identify the competencies measured by the instruments for HBC nurses. The psychometric properties of instruments in development and psychometric testing design studies were also examined. The methodological quality of the studies was evaluated using the Medical Education Research Study Quality Instrument and COSMIN checklist accordingly. DATA SOURCES: Relevant studies were searched on CINAHL, MEDLINE (via PubMed), EMBASE, PsychINFO and Scopus from 2000 to 2022. The search was limited to full-text items in the English language. RESULTS: A total of 23 studies reporting 24 instruments were included. 12 instruments were adopted or modified by the studies while the other 12 were developed and psychometrically tested by the studies. None of the instruments encompassed all of the 10 home-based nursing care competencies identified in an earlier study. The two most frequently measured competencies were the management of health conditions, and critical thinking and problem-solving skills, while the two least measured competencies were quality and safety, and technological literacy. The content and structural validity of most instruments were inadequate since the adopted instruments were not initially designed or tested among HBC nurses. CONCLUSION: This review provides a consolidation of existing instruments that were used to assess HBC nurses' competencies. The instruments were generally not comprehensive, and the content and structural validity were limited. Nonetheless, the domains, items and approaches to instrument development could be adopted to develop and test a comprehensive competency instrument for home-based nursing care practice in the future. IMPACT: This review consolidated instruments used to measure home-based care nurses' competency. The instruments were often designed for ward-based care nurses hence a comprehensive and validated home-based nursing care competency instrument is needed. Nurses, researchers and nursing leaders could consider the competency instruments identified in this review to measure nurses' competencies, while a home-based nursing care competency scale is being developed. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was required in this review.
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The lack of intuitive and active human-robot interaction makes it difficult to use upper-limb-assistive devices. In this paper, we propose a novel learning-based controller that intuitively uses onset motion to predict the desired end-point position for an assistive robot. A multi-modal sensing system comprising inertial measurement units (IMUs), electromyographic (EMG) sensors, and mechanomyography (MMG) sensors was implemented. This system was used to acquire kinematic and physiological signals during reaching and placing tasks performed by five healthy subjects. The onset motion data of each motion trial were extracted to input into traditional regression models and deep learning models for training and testing. The models can predict the position of the hand in planar space, which is the reference position for low-level position controllers. The results show that using IMU sensor with the proposed prediction model is sufficient for motion intention detection, which can provide almost the same prediction performance compared with adding EMG or MMG. Additionally, recurrent neural network (RNN)-based models can predict target positions over a short onset time window for reaching motions and are suitable for predicting targets over a longer horizon for placing tasks. This study's detailed analysis can improve the usability of the assistive/rehabilitation robots.
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Robótica , Humanos , Intención , Electromiografía/métodos , Extremidad Superior/fisiología , Movimiento (Física)RESUMEN
An oligonucleotide DNA probe has been developed for the application in the DNA electrochemical biosensor for the early diagnosis of coronavirus disease (COVID-19). Here, the virus microRNA from the N-gene of severe acute respiratory syndrome-2 (SARS-CoV-2) was used for the first time as a specific target for detecting the virus and became a framework for developing the complementary DNA probe. The sequence analysis of the virus microRNA was carried out using bioinformatics tools including basic local alignment search tools, multiple sequence alignment from CLUSTLW, microRNA database (miRbase), microRNA target database, and gene analysis. Cross-validation of distinct strains of coronavirus and human microRNA sequences was completed to validate the percentage of identical and consent regions. The percent identity parameter from the bioinformatics tools revealed the virus microRNAs' sequence has a 100% match with the genome of SARS-CoV-2 compared with other coronavirus strains, hence improving the selectivity of the complementary DNA probe. The 30 mer with 53.0% GC content of complementary DNA probe 5' GCC TGA GTT GAG TCA GCA CTG CTC ATG GAT 3' was designed and could be used as a bioreceptor for the biosensor development in the clinical and environmental diagnosis of COVID-19.
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Técnicas Biosensibles , COVID-19 , MicroARNs , COVID-19/diagnóstico , Sondas de ADN , ADN Complementario , Genoma Viral , Humanos , MicroARNs/genética , SARS-CoV-2/genéticaRESUMEN
BACKGROUND: Psychiatric pharmaceutical care is the provision of pharmaceutical care services to patients with psychiatric related illnesses or disorders. Several studies have demonstrated the positive influence psychiatric pharmaceutical care on patients' clinical, humanistic and economic outcomes. This study aimed to examine the extent of psychiatric pharmaceutical care practice in a convenience sample of Malaysian government hospitals and the barriers to the provision of these services. METHODS: An anonymous cross-sectional survey of registered pharmacists working at a convenience sample of government hospitals in Malaysia was undertaken from September 2019 to June 2020. RESULTS: Pharmacists frequently ensured the appropriateness of the dose (55%), dosage form (47%) and dosing schedule (48%) of the dispensed medications. Most pharmacists infrequently worked with patients and healthcare professionals to develop a pharmacotherapeutic regimen and a corresponding monitoring plan (28%). There was no statistically significant difference in the provision of pharmaceutical care services with respect to gender, age, years of practice, and professional board certification. However, the services offered were influenced by the respondent's education and pharmacy setting. The obstacles perceived by pharmacists included lack of time (89%), shortage of pharmacy staff (87%), the patients' inability to comprehend medical information (85%), insufficient demand and acceptance by patients (82%), the lack of official policies and standardised practice protocols (78%), inaccessibility to the patients' medical records (77%) and the lack of structured communication channels between pharmacists and physicians (75%), the pharmacists lack of knowledge/skills and confidence (78%) and insufficient recognition from physicians to the pharmacists' skills (76%). CONCLUSIONS: This is the first study to explore the extent and barriers of psychiatric pharmaceutical care in Malaysian hospitals; it highlighted the need for mobilising pharmacists to expand these services.
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Servicios Comunitarios de Farmacia , Servicios Farmacéuticos , Médicos , Actitud del Personal de Salud , Estudios Transversales , Hospitales , Humanos , Farmacéuticos , Rol Profesional , Encuestas y CuestionariosRESUMEN
BACKGROUND: Insightful feedback generation for daily home-based stroke rehabilitation is currently unavailable due to the inefficiency of exercise inspection done by therapists. We aim to produce a compact anomaly representation that allows a therapist to pay attention to only a few specific sections in a long exercise session record and boost their efficiency in feedback generation. METHODS: This study proposes a data-driven technique to model a repetitive exercise using unsupervised phase learning on an artificial neural network and statistical learning on principal component analysis (PCA). After a model is built on a set of normal healthy movements, the model can be used to extract a sequence of anomaly scores from a movement of the same prescription. RESULTS: The method not only works on a standard marker-based motion capture system but also performs well on a more compact and affordable motion capture system based-on Kinect V2 and wrist-worn inertial measurement units that can be used at home. An evaluation of four different exercises shows its potential in separating anomalous movements from normal ones with an average area under the curve (AUC) of 0.9872 even on the compact motion capture system. CONCLUSIONS: The proposed processing technique has the potential to help clinicians in providing high-quality feedback for telerehabilitation in a more scalable way.
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Terapia por Ejercicio , Rehabilitación de Accidente Cerebrovascular , Ejercicio Físico , Terapia por Ejercicio/métodos , Humanos , Movimiento , Extremidad SuperiorRESUMEN
Piezo-actuated flexure-based systems are widely used in applications with high accuracy requirements, but the intrinsic hysteresis has a detrimental effect on the performance which should be compensated. Conventional models were presented to model this undesired effect using additional dead-zone operators. This paper presents a new approach using two sets of operators with a distributed compensator to model and compensate for the asymmetric system hysteresis based on inversion calculation with a simplified digitized representation. The experimental results validate the effectiveness of the proposed model in modeling and compensating the asymmetric system hysteresis.
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Gait evaluation is important in gait rehabilitation and assistance to monitor patient's balance status and assess recovery performance. Recent technologies leverage on vision-based systems with high portability and low operational complexity. In this paper, we propose a new vision-based foot tracking algorithm specially catering to overground gait assistive devices, which often have limited view of the users. The algorithm models the foot and the shank of the user using simple geometry. Through cost optimization, it then aligns the models to the point cloud, showing the back view of the user's lower limbs. The system outputs the poses of the feet, which are used to compute the spatial-temporal gait parameters. Seven healthy young subjects are recruited to perform overground and treadmill walking trials. The results of the algorithm are compared with the motion capture system and a third-party gait analysis software. The algorithm has a fitting rotational and translational errors of less than 20 degrees and 33 mm, respectively, for 0.4 m/s walking speed. The gait detection F1 score achieves more than 96.8%. The step length and step width errors are around 35 mm, while the cycle time error is less than 38 ms. The proposed algorithm provides a fast, contactless, portable, and cost-effective gait evaluation method without requiring the user to wear any customized footwear.
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Pie , Caminata , Fenómenos Biomecánicos , Marcha , Análisis de la Marcha , Humanos , Extremidad InferiorRESUMEN
AIMS: This review aims to examine the prevalence estimate of low resilience among health care professionals and identify the factors affecting the prevalence. BACKGROUND: Health care professionals experience high levels of stress. Understanding the health care professionals' resilience may provide an insight into how they perform in a highly stressed environment. EVALUATION: A comprehensive search of 11 databases was conducted. Studies that provided prevalence rates for low resilience among health care professionals working in a health care setting were included. Meta-analyses, sensitivity, subgroup analyses and meta-regression were conducted. KEY ISSUES: Among 27,720 studies, 41 studies (N = 17,073) across 16 countries were included. The prevalence of low resilience was 26% (95% CI: 20-32). Subgroup analyses indicated that types of resilience measures affect resilience prevalence significantly. A higher prevalence of low resilience was observed among allied health professions during the COVID-19 pandemic in the Middle East. CONCLUSIONS: This review indicated the prevalence of low resilience and type of resilience measurement instruments that affected the prevalence. IMPLICATIONS FOR NURSING MANAGEMENT: This review provides a roadmap to design tailored, discipline-specific and sustainable resilience training for nurses. Nursing managers should monitor the working hours and workload of nursing staffing in order to provide a protective working environment. This is a systematic review, and the PROSPERO registration number is CRD42021235350.
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COVID-19 , Pandemias , COVID-19/epidemiología , Personal de Salud , Humanos , Prevalencia , Lugar de TrabajoRESUMEN
Resilience has been documented as an essential component in managing stress. However, understanding how undergraduate students with different sociodemographic characteristics perceive resilience remains understudied. This study aimed to explore how undergraduate students in one university define and build resilience during the COVID-19 pandemic. Students' perception and preferences for receiving resilience training were additionally solicited. A descriptive qualitative cross-sectional study was conducted. Twenty-seven students were interviewed using a semi-structured interview guide via Skype instant messaging. The thematic analysis generated five themes: resilience as enduring and withstanding; the building blocks of resilience; resilience: learning or earning; pedagogical considerations for resilience training; and a blended platform for resilience training. Participants described resilience as an enduring and withstanding trait essential for university students. Resilience can be built from intrinsic and extrinsic factors. Intrinsic factors that enhanced resilience included desire to succeed and motivation. Extrinsic factors were relational in nature, and friends, family, teachers, and religion were found to boost resilience. Students had several recommendations in designing resilience training, and they recommended the use of a blended platform. Further, students suggested the use of videos, narratives from resilient individuals, and using reflective practice as a pedagogy in resilience training. Future resilience training should consist of personal and interpersonal factors and should be introduced early during the academic term of students' university life. As the COVID-19 pandemic compounds an already challenging academic climate, this study lends it findings to expand the resilience literature and develop future resilience training.
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Background/Purpose: To date, there are no published validated Chinese versions of the incremental shuttle walk test (ISWT) instructions despite its wide clinical applications. Translation of the Chinese ISWT instruction is done in an ad-hoc manner within the Chinese-speaking populations, affecting the test's reliability and validity since translation can differ significantly between individuals. This warrants the need for psychometric testing of such translation. Objectives: To develop a Chinese (Mandarin) version of the ISWT instructions (ISWT-CHN) that is conceptually equivalent to the original English version (ISWT-ENG) and establish its reliability and validity. Methods: Forward and backward translations from the ISWT-ENG were done to generate the ISWT-CHN. Face and content validity was determined during the translation process. Intra-rater and inter-rater reliability of the ISWT-CHN, construct and criterion validity were established by analysing the ISWT and the gold standard cardiopulmonary exercise test results. Results: The Item-Content validity index (I-CVI), Scale-level-Content validity index (S-CVI), and content validity ratio (CVR) of the ISWT-CHN were 1.0. Intra-class Correlation Coefficient (ICC) for inter-rater reliability between two raters were excellent (ICC=0.99, 95% CI 0.97-1.0, p<0.001; SEM=0.85 m, MDC=2.35 m). The intra-rater reliability of both Raters A (ICC=0.92, 95% CI 0.53-0.98, p=0.003; SEM=35 m, MDC=97 m) and B (ICC=0.90, 95% CI 0.76-0.96, p<0.001; SEM=32 m, MDC=88 m) were good. In a sample of 32 healthy participants, both ISWT-CHN and ISWT-ENG instruction results showed low-positive correlations with the VO2max determined from the cardiopulmonary exercise test (r = 0.439, p<0.001; r=0.448, p<0.001). There is a very high correlation between ISWT-ENG and ISWT-CHN results with no statistically significant differences (r=0.967, p<0.001). The construct and criterion validity of the ISWT-CHN were established. Conclusion: This study developed the ISWT-CHN and showed that it is a valid and reliable measure conceptually comparable to the ISWT-ENG. It will benefit the determination of functional exercise capacity in Chinese-speaking populations. Key messages: â¢This study is aimed to develop a Chinese (Mandarin) version of the ISWT instructions.â¢The ISWT Chinese translation is valid and reliable that is conceptually comparable to the original English instruction.â¢The translated ISWT-Chinese instruction will enable the use of ISWT among the Chinese-speaking populations.
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Deregulated expression of the MYC transcription factor occurs in most human cancers and correlates with high proliferation, reprogrammed cellular metabolism and poor prognosis. Overexpressed MYC binds to virtually all active promoters within a cell, although with different binding affinities, and modulates the expression of distinct subsets of genes. However, the critical effectors of MYC in tumorigenesis remain largely unknown. Here we show that during lymphomagenesis in Eµ-myc transgenic mice, MYC directly upregulates the transcription of the core small nuclear ribonucleoprotein particle assembly genes, including Prmt5, an arginine methyltransferase that methylates Sm proteins. This coordinated regulatory effect is critical for the core biogenesis of small nuclear ribonucleoprotein particles, effective pre-messenger-RNA splicing, cell survival and proliferation. Our results demonstrate that MYC maintains the splicing fidelity of exons with a weak 5' donor site. Additionally, we identify pre-messenger-RNAs that are particularly sensitive to the perturbation of the MYC-PRMT5 axis, resulting in either intron retention (for example, Dvl1) or exon skipping (for example, Atr, Ep400). Using antisense oligonucleotides, we demonstrate the contribution of these splicing defects to the anti-proliferative/apoptotic phenotype observed in PRMT5-depleted Eµ-myc B cells. We conclude that, in addition to its well-documented oncogenic functions in transcription and translation, MYC also safeguards proper pre-messenger-RNA splicing as an essential step in lymphomagenesis.
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Regulación Neoplásica de la Expresión Génica , Linfoma/fisiopatología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Precursores del ARN/metabolismo , Empalme del ARN/fisiología , Animales , Exones/genética , Células HEK293 , Humanos , Intrones/genética , Ratones , Oligonucleótidos Antisentido/metabolismo , Proteína Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas , Proteínas Proto-Oncogénicas c-myc/genéticaRESUMEN
PURPOSE: Cancer survivors continue to experience issues that persist across the survivorship trajectory. This study aims to explore the relationship among survivorship care need, symptom experience, and quality of life (QoL) of multiethnic cancer survivors by using path analytic methods. METHODS: Participants were recruited from an academic medical center in Singapore that provides inpatient and outpatient oncology and hematology service. The Cancer Survivor Unmet Needs measure, physical effects subscale of the Cancer Survivors' Survey of Needs tool, and a Global QoL 10-point Likert scale were used to identify survivorship care needs, symptom experience, and QoL. Descriptive statistics were used to compute sociodemographic information, total survivorship needs, symptom experienced, and quality of life scores. The symptom experience model was used as the hypothetical model. The Analysis of Moment Structure was used to conduct the path analysis to evaluate the relationship between survivorship care needs, symptom experience, and quality of life. RESULTS: Older cancer survivors were more likely to have spent a longer duration having cancer. Males were unlikely to suffer from solid tumor malignancies. Survivors with solid tumor malignancies were less likely to require supportive care. Survivors who require more supportive care were more likely to have a greater symptom burden. Cancer survivors with more symptoms have poorer QoL. The findings from this study partially supported the symptom experience model. CONCLUSIONS: Our findings reveal that cancer survivors continue to experience symptoms across the survivorship trajectory. The results provide information for nurses during the planning and execution of survivorship care.
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Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias/etnología , Calidad de Vida/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To present an overview of how artificial intelligence (AI) could be used to regulate eating and dietary behaviours, exercise behaviours and weight loss. DESIGN: A scoping review of global literature published from inception to 15 December 2020 was conducted according to Arksey and O'Malley's five-step framework. Eight databases (CINAHL, Cochrane-Central, Embase, IEEE Xplore, PsycINFO, PubMed, Scopus and Web of Science) were searched. Included studies were independently screened for eligibility by two reviewers with good interrater reliability (k = 0·96). RESULTS: Sixty-six out of 5573 potential studies were included, representing more than 2031 participants. Three tenets of self-regulation were identified - self-monitoring (n 66, 100 %), optimisation of goal setting (n 10, 15·2 %) and self-control (n 10, 15·2 %). Articles were also categorised into three AI applications, namely machine perception (n 50), predictive analytics only (n 6) and real-time analytics with personalised micro-interventions (n 10). Machine perception focused on recognising food items, eating behaviours, physical activities and estimating energy balance. Predictive analytics focused on predicting weight loss, intervention adherence, dietary lapses and emotional eating. Studies on the last theme focused on evaluating AI-assisted weight management interventions that instantaneously collected behavioural data, optimised prediction models for behavioural lapse events and enhance behavioural self-control through adaptive and personalised nudges/prompts. Only six studies reported average weight losses (2·4-4·7 %) of which two were statistically significant. CONCLUSION: The use of AI for weight loss is still undeveloped. Based on the current study findings, we proposed a framework on the applicability of AI for weight loss but cautioned its contingency upon engagement and contextualisation.