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BACKGROUND: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices. METHODS: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression. RESULTS: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3. CONCLUSION: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms.
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Early diagnosis and intervention are pivotal in reducing colorectal cancer (CRC) incidence and enhancing patient outcomes. In this study, we focused on three genes, AQP8, GUCA2B, and SPIB, which exhibit high coexpression and play crucial roles in suppressing early-stage CRC. Our objective was to identify key miRNAs that can mitigate CRC tumorigenesis and modulate the coexpression network involving these genes. We conducted a comprehensive analysis using large-scale tissue mRNA data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus to validate the coexpression of AQP8, GUCA2B, and SPIB, and to assess their diagnostic and prognostic significance in CRC. The mRNA-miRNA interactions were examined using MiRNet and the Encyclopedia of RNA Interactomes. Furthermore, using various molecular techniques, we conducted miRNA inhibitor transfection experiments in HCT116 cells to evaluate their effects on cell growth, migration, and gene/protein expression. Our findings revealed that, compared with normal tissues, AQP8, GUCA2B, and SPIB exhibited high coexpression and were downregulated in CRC, particularly during tumorigenesis. OncoMirs, hsa-miR-182-5p, and hsa-miR-27a-3p, were predicted to regulate these genes. MiRNA inhibition experiments in HCT116 cells demonstrated the inhibitory effects of miR-27a-3p and miR-182-5p on GUCA2B mRNA and protein expression. These miRNAs promoted the proliferation of CRC cells, possibly through their involvement in the GUCA2B-GUCY2C axis, which is known to promote tumor growth. While the expressions of AQP8 and SPIB were barely detectable, their regulatory relationship with hsa-miR-182-5p remained inconclusive. Our study confirms that hsa-miR-27a-3p and hsa-miR-182-5p are oncomiRs in CRC. These miRNAs may contribute to GUCY2C dysregulation by downregulating GUCA2B, which encodes uroguanylin. Consequently, hsa-miR-182-5p and hsa-miR-27a-3p show promise as potential targets for early intervention and treatment in the early stages of CRC.
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Objective: Weekend sleep duration is linked to health issues, including mortality. However, how weekend sleep duration can impact chronic kidney disease (CKD) still needs to be understood. Therefore, we aimed to analyze how weekend sleep duration is associated with kidney function. Methods: This is a cross-sectional study. Data were obtained from the 2017-2018 National Health and Nutrition Examination Survey. We included 5362 study participants and categorized them into nine subgroups by sleep duration (short: ≤6 hours, normal: 6-9 hours, and long: ≥9 hours) on weekdays and weekends and analyzed for the respective association with renal function using stratified multivariable linear regression. Results: Weekend sleep duration for 9 hours or more was associated with decreasing estimated glomerular filtration rate (eGFR) levels by 2.8 to 6.4 mL/min/1.73 m2 among people with long to short weekday sleep duration compared with short weekday and weekend sleep durations (control group) after adjusting for demographic characteristics, body measurement, sleep quality, smoking, and comorbidities. The study population with short weekday sleep duration (sWK) and long weekend sleep duration (lWD) had the most significant decline in eGFR. For the study population with sWK, eGFR level significantly decreased by 1.1 mL/min/1.73 m2 as sleep duration on weekends increased by one hour. Conclusion: The underlying mediators of lWD and CKD could be the dysregulation of human behaviors, metabolism, or biological functions. Longer weekend sleep duration was linked to a decrease in eGFR levels. It warrants further study to clarify the mediators.
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In early-stage colorectal cancer (CRC), AQP8, GUCA2B, and SPIB were important suppressor genes and frequently co-expressed. However, the underlying co-regulation effect remains unknown and need to be elucidated. We aimed to investigate the co-regulatory network of AQP8, GUCA2B, and SPIB in CRC using in vitro and in silico methods. Q-PCR, western blot, and immunohistochemistry were used to assess the co-regulatory network of the target genes in the HCT-116 cell line and fresh tumor tissues. Bioinformatical methods were used to validate the findings using the Cancer Genome Atlas COlon ADenocarcinoma and REctum ADenocarcinoma datasets, as well as large scale integrated data sets from Gene Expression Omnibus. In clinical CRC tissues, SPIB, AQP8, and GUCA2B were barely expressed compared to normal mucosa. When compared to 22 well-known genetic biomarkers, they are independent predictors of CRC identification with near 100% accuracy. In the co-regulatory network, they were co-upregulated at the mRNA and protein expression levels. AQP8, GUCA2B and SPIB were linked to immune cell infiltration and GUCA2B and SPIB were negatively associated with tumor purity. The co-regulatory network in miRNA-mRNA analysis was mediated by cancer-related microRNAs miR-182-5p and miR-27a-3. The functional analysis of the co-regulatory network's protein-protein interaction networks reveals three clusters and three major functions: complex interactions of transcription factors in mediating cytokine biology in T cells (SPIB cluster), guanylin, and Intestinal infectious diseases (GUCA2B cluster), and water channel activity balance (AQP8 cluster). The co-regulatory network of SPIB, AQP8, and GUCA2B was confirmed. MiR-27a-3p and miR-182-5p were two possible mediators. The mechanisms of SPIB, AQP8, GUCA2B, miR-182-5p, and miR-27a-3p in CRC merit further investigation.
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Gene expression signatures provide valuable information to guide postoperative treatment in breast cancer (BC) patients. However, genetic tests are prohibitively expensive for the majority of BC patients. Immunohistochemical staining (IHC) subtype classification system has been widely used for treatment guideline and is affordable to most BC patients. We aimed to revise immunohistochemical staining (IHC) subtyping to better match gene expression-based Prediction Analysis of Microarray 50 (PAM50) subtyping. Real world data of 372 BC patients were recruited in the Tri-Service General Hospital between Jan 2019 and Dec 2021. Clinical pathological information, blood, twelve pathological tissue slide samples, and fresh surgical tumor specimens were collected to examine IHC and PAM50. Current IHC subtyping (cIHC) tends to misclassify PAM50-based luminal A (lum A) to luminal B (lum B) by 35.81%, PAM50-lum B to PAM50-lum A by 9.09%, PAM50-Her2-enriched to lum B by 61.11%, PAM50-based Her2-enriched to lum B by 61.11%, and PAM50-based basal-like to lum B by 33.33%. We used random forest to identify estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and Ki-67 status as the best indicators for revised IHC subtyping (rIHC4) and revised the classification rules by stratified analysis and prediction efficacy. rIHC4 increased the concordance rate for PAM50 subtypes from 68.3% to 74.7%. Both sensitivity and precision increased in most rIHC4 subtypes. Sensitivity increased from 33.3% to 87.4% in the Her2-enriched subtype; precision increased more evidently in the basal-like and lum B subtypes, from 71.4% to 83.3% and 57% to 65.1%, respectively. Our rIHC4 subtyping improved consistency with the PAM50 subtype, which could improve clinical management of BC patients without increasing medical expense.
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The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.
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Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis. Particularly, individuals with the TT allele at rs9373441 exhibited a more favorable response, characterized by a significant increase in FOXP3 + Treg and Type 1 regulatory T cells (Tr1) (p = 0.04, 0.02) and a decrease in Effector T helper cells (Effector Th) (p = 0.03). The GATA3-GCM2-PTH and GATA3-FOXO1-FOXP3 pathways were implicated. RNA-sequencing (RNA-seq) analysis revealed increased expression levels of UTRN, PTH2R, FOXO1, and FOXO3 in good and moderate responders (p = 0.01, 0.03, 0.0005, and 0.02). Notably, the change in FOXP3 + Treg and Tr1 was positively correlated with UTRN expression (both p = 0.03). These findings underscore the critical link between rs9373441 and the response to csDMARDs, empowering clinicians to tailor treatments for enhanced outcomes in patients with RA.
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Antirreumáticos , Artritis Reumatoide , Humanos , Antirreumáticos/metabolismo , Antirreumáticos/uso terapéutico , Linfocitos T Reguladores , Estudio de Asociación del Genoma Completo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Resultado del Tratamiento , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismoRESUMEN
BACKGROUND: ChatGPT is a powerful pretrained large language model. It has both demonstrated potential and raised concerns related to knowledge translation and knowledge transfer. To apply and improve knowledge transfer in the real world, it is essential to assess the perceptions and acceptance of the users of ChatGPT-assisted training. OBJECTIVE: We aimed to investigate the perceptions of health care trainees and professionals on ChatGPT-assisted training, using biomedical informatics as an example. METHODS: We used purposeful sampling to include all health care undergraduate trainees and graduate professionals (n=195) from January to May 2023 in the School of Public Health at the National Defense Medical Center in Taiwan. Subjects were asked to watch a 2-minute video introducing 5 scenarios about ChatGPT-assisted training in biomedical informatics and then answer a self-designed online (web- and mobile-based) questionnaire according to the Kirkpatrick model. The survey responses were used to develop 4 constructs: "perceived knowledge acquisition," "perceived training motivation," "perceived training satisfaction," and "perceived training effectiveness." The study used structural equation modeling (SEM) to evaluate and test the structural model and hypotheses. RESULTS: The online questionnaire response rate was 152 of 195 (78%); 88 of 152 participants (58%) were undergraduate trainees and 90 of 152 participants (59%) were women. The ages ranged from 18 to 53 years (mean 23.3, SD 6.0 years). There was no statistical difference in perceptions of training evaluation between men and women. Most participants were enthusiastic about the ChatGPT-assisted training, while the graduate professionals were more enthusiastic than undergraduate trainees. Nevertheless, some concerns were raised about potential cheating on training assessment. The average scores for knowledge acquisition, training motivation, training satisfaction, and training effectiveness were 3.84 (SD 0.80), 3.76 (SD 0.93), 3.75 (SD 0.87), and 3.72 (SD 0.91), respectively (Likert scale 1-5: strongly disagree to strongly agree). Knowledge acquisition had the highest score and training effectiveness the lowest. In the SEM results, training effectiveness was influenced predominantly by knowledge acquisition and partially met the hypotheses in the research framework. Knowledge acquisition had a direct effect on training effectiveness, training satisfaction, and training motivation, with ß coefficients of .80, .87, and .97, respectively (all P<.001). CONCLUSIONS: Most health care trainees and professionals perceived ChatGPT-assisted training as an aid in knowledge transfer. However, to improve training effectiveness, it should be combined with empirical experts for proper guidance and dual interaction. In a future study, we recommend using a larger sample size for evaluation of internet-connected large language models in medical knowledge transfer.
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Inteligencia Artificial , Actitud del Personal de Salud , Estudiantes , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Medicina , Percepción , Encuestas y Cuestionarios , TaiwánRESUMEN
Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.
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Personal Militar , Femenino , Humanos , Autoinforme , Cotinina , Estudios Transversales , Fumar , VoluntariosRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility. We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan. METHODS: Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case-control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS. RESULTS: The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk. CONCLUSION: A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.
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Estudio de Asociación del Genoma Completo , Espondilitis Anquilosante , Humanos , Antígeno HLA-B27/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/patologíaRESUMEN
Background: The Taiwanese military trains smoking cessation counselors to counsel officers and soldiers on quitting smoking as part time. The intention to stay among smoking cessation counselors affects the promotion of smoking cessation. This study investigated smoking cessation counselors' intention to stay by applying a conceptual model of intent to stay (CMIS) to analyze influencing factors. Methods: In this cross-sectional study, we applied the CMIS to design a questionnaire. We invited 577 smoking cessation counselors trained in the military from 2016 to 2017. The response rate was 46.7%, and the questionnaire responses of 260 military smoking cessation counselors were analyzed. We used path analysis to verify the relationships among the various aspects of the CMIS. Results: We determined that smoking cessation counselors' intention to stay is directly affected by job satisfaction (ß = 0.150, p = 0.014), job stress (ß = -0.225, p < 0.001), and institutional identification (ß = 0.431, p < 0.001). Career opportunities indirectly affect intention to stay through institutional identification, working environment indirectly affects intention to stay through job stress, and co-worker support and self-fulfillment indirectly affect intention to stay through job satisfaction and institutional identification. Our model could explain 36.7% of the variance in intent to stay among smoking cessation counselors. Conclusion: Our results suggest that relevant policies should be formulated to enhance smoking cessation counselors' recognition, affirmation, and sense of belonging as related to smoking cessation counseling work, thereby raising their institutional identification and promoting their intention to stay.
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Consejeros , Estrés Laboral , Cese del Hábito de Fumar , Consejeros/psicología , Estudios Transversales , Humanos , Intención , Cese del Hábito de Fumar/métodos , Cese del Hábito de Fumar/psicologíaRESUMEN
BACKGROUND: The association between elevated serum uric acid (UA) levels and the risk of developing colonic diverticulosis has not yet been investigated. Thus, this cross-sectional study aimed to examine this correlation in individuals from Taiwan. METHODS: From Jan. 1, 2010, to Dec. 31, 2016., approximately 5,605 patients (aged >20 years) from Tri-Service General Hospital who met the inclusion criteria according to colonoscopy and laboratory test findings were included in this research. The correlation between serum UA levels and colonic diverticulosis was investigated via regression analyses. RESULTS: Participants with elevated serum UA levels were at a higher risk of colonic diverticulosis. The area under the curve for serum UA levels was significantly higher in women than in men (0.651 [95% confidence interval: 0.596-0.707] vs. 0.55 [0.507-0.593]). There were specific trends in female-specific indicators for colonic diverticulosis across increasing quartiles of serum UA levels. CONCLUSIONS: Patients with elevated serum UA levels should be cautious regarding the development of colonic diverticulosis disorder in female. Moreover, prospective studies may provide additional information on the relationship between elevated serum UA levels and colonic diverticulosis.
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Diverticulosis del Colon , Ácido Úrico , Colonoscopía , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de RiesgoRESUMEN
Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith-Waterman and Needleman-Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.
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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has become a global pandemic since December 2019. Most of the patients are mild or asymptomatic and recovered well as those suffered from other respiratory viruses. SARS-CoV-2 infection is supposed to demonstrate more sequelae. Acute kidney injury (AKI) is common among COVID-19 patients and is associated with disease severity and outcomes. Only a few studies focused on a detailed analysis of kidney damage in asymptomatic or mildly symptomatic COVID-19 patients. Whether any minor viral infection is likely to exhibit similar minor effect on renal function as COVID-19 is still unclear, and the definite pathophysiology of viral invasion is not fully understood. Currently, the proposed mechanisms of AKI include direct effects of virus on kidney, dysregulated immune response, or as a result of multi-organs failure have been proposed. This study will discuss the difference between COVID-19 and other viruses, focusing on proposed mechanisms, biomarkers and whether it matters with clinical significance.
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Lesión Renal Aguda , COVID-19 , Virosis , COVID-19/complicaciones , Humanos , Riñón/fisiología , SARS-CoV-2RESUMEN
BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.
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BACKGROUND: Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development. METHODS: We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a 'pathway/gene-set analysis' approach. RESULTS: The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma. CONCLUSION: In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.
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Antipsicóticos , Neoplasias Encefálicas , Glioblastoma , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , HumanosRESUMEN
Adolescents' Internet health information usage has rarely been investigated. Adolescents seek all kinds of information from the Internet, including health information, which affects their Health Literacy that eHealth Literacy (eHL). This study is a retrospective observational study, we have total of 500 questionnaires were distributed, 87% of which were recovered, and we explored the channels that adolescents use to search for health information, their ability to identify false information, and factors affecting the type and content of health information queried. Adolescents believe that the Internet is a good means to seek health information because of its instant accessibility, frequent updating, convenience, and lack of time limits. More boys use the Internet to seek health information than girls in junior high schools (p = 0.009). The Internet is an important source of health information for adolescents but contains extensive misinformation that adolescents cannot identify. Additionally, adolescent boys and girls are interested in different health issues. Therefore, the government should implement measures to minimize misinformation on the Internet and create a healthy, educational online environment to promote Adolescents' eHealth Literacy (eHL).
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Alfabetización en Salud , Telemedicina , Adolescente , Estudios Transversales , Femenino , Alfabetización en Salud/métodos , Humanos , Internet , Masculino , Encuestas y Cuestionarios , Taiwán , Telemedicina/métodosRESUMEN
Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29-1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.
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Melatonin is a hormone majorly secreted by the pineal gland and contributes to a various type of physiological functions in mammals. The melatonin production is tightly limited to the AANAT level, yet the most known molecular mechanisms underlying AANAT gene transcription is limited in the pinealocyte. Here, we find that c-Fos and cAMP-response element-binding protein (CREB) decreases and increases the AANAT transcriptional activity in renal tubular epithelial cell, respectively. Notably, c-Fos knockdown significantly upregulates melatonin levels in renal tubular cells. Functional results indicate that AANAT expression is decreased by c-Fos and resulted in enhancement of cell damage in albumin-injury cell model. We further find an inverse correlation between c-Fos and AANAT levels in renal tubular cells from experimental membranous nephropathy (MN) samples and clinical MN specimens. Our finding provides the molecular basis of c-Fos in transcriptionally downregulating expression of AANAT and melatonin, and elucidate the protective role of AANAT in preventing renal tubular cells death in albumin-injury cell model and MN progression.
Asunto(s)
N-Acetiltransferasa de Arilalquilamina/genética , Regulación hacia Abajo , Células Epiteliales/metabolismo , Glomerulonefritis Membranosa/genética , Proteínas Proto-Oncogénicas c-fos/genética , Animales , N-Acetiltransferasa de Arilalquilamina/metabolismo , Línea Celular , Células Cultivadas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis Membranosa/patología , Células HEK293 , Humanos , Túbulos Renales/citología , Melatonina/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Activación TranscripcionalRESUMEN
Study Objectives: Smoking and sleep are modifiable factors associated with the chronic kidney diseases. However, the interaction of smoking and sleep on the renal function are still unclear. Therefore, we aimed to evaluate the interactive impacts of smoking and sleep on the renal function. Methods: Data were obtained from the National Health and Nutrition Examination Survey. The study population were categorized into nine subgroups by smoking (smoking every day, sometimes, and non-smokers recently) and sleep duration (short duration ≤ 6 h, normal duration 6-9 h, and longer duration ≥ 9 h on the weekdays). Results: The study group with a short sleep duration had significantly higher serum cotinine and hydrocotinine levels compared with the other two sleep groups. After adjusting the demographic characteristics (age, race, body mass index, and marital status), sleep quality (snoring or breathing cessation), and comorbidities (diabetes mellitus, hypertension, high cholesterol, anemia, congestive heart failure, coronary heart disease, and stroke), non-smokers with short or long sleep duration had significant lower estimated glomerular filtration rate (eGFR) levels than the study group who smoked every day and slept ≤ 6 h. The effects of sleep duration on eGFR levels varied with smoking status. For the study group smoking every day, eGFR levels increased as sleep duration decreased, whereas for the study group smoking sometimes, eGFR levels increased as sleep duration increased. The U-shaped effects of eGFR levels were observed among non-smokers whose normal sleep duration was associated with better eGFR levels. Normal sleep duration was an important protective factor of the renal function for non-smokers than smokers. Conclusions: The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers.