High-throughput approaches for profiling the 5′ ends of RNA degradation intermediates on a genome-wide scale are frequently applied to analyze and validate cleavage sites guided by microRNAs ...(miRNAs). However, the complexity of the RNA degradome other than miRNA targets is currently largely uncharacterized, and this limits the application of RNA degradome studies. We conducted a global analysis of 5′-truncated mRNA ends that mapped to coding sequences (CDSs) of Arabidopsis thaliana, rice (Oryza sativa), and soybean (Glycine max). Based on this analysis, we provide multiple lines of evidence to show that the plant RNA degradome contains in vivo ribosome-protected mRNA fragments. We observed a 3-nucleotide periodicity in the position of free 5′ RNA ends and a bias toward the translational frame. By examining conserved peptide upstream open reading frames (uORFs) of Arabidopsis and rice, we found a predominance of 5′ termini of RNA degradation intermediates that were separated by a length equal to a ribosome-protected mRNA fragment. Through the analysis of RNA degradome data, we discovered uORFs and CDS regions potentially associated with stacked ribosomes in Arabidopsis. Furthermore, our analysis of RNA degradome data suggested that the binding of Arabidopsis ARGONAUTE7 to a noncleavable target site of miR390 might directly hinder ribosome movement. This work demonstrates an alternative use of RNA degradome data in the study of ribosome stalling.
To investigate the protective behaviours of longer near work distance, discontinuing near work and more time outdoors in recess from parent self-report in the myopia prevalence and progression among ...myopic children aged 9-11 years.
Myopia Investigation study in Taipei is a longitudinal population-based study that enrolled elementary school students in Taipei. We provided vision and refraction examination every 6 months. Spherical equivalent (SE) of cycloplegic refraction ≤-0.50 Diopter (D) is defined as myopia. Total 10 743 (70.4%) students completed 2-year refraction data and questionnaire. The myopia prevalence and progression (difference of SE) in baseline, 6, 12, 18 and 24 months were compared by generalised estimating equations.
Children with persistent protective behaviour had significant lower prevalence of myopia. The protective impact was statistically significant from 6 to 24 months. In 2 years follow-up, risk ratio after adjusting the background variables and the other two behaviours in near work distance, near work time and outdoor time were 0.71, 0.89 and 0.77. In SE analysis, after adjusting the other two behaviours, near work distance >30 cm (-0.7 vs -1.04 D; p
0.001), discontinuing near work every 30 min (-0.77 vs -0.96 D, p=0.005) and more time outdoors in recess from parent self-report (-0.75 vs -0.98 D; p=0.012) revealed protective impacts on diminishing myopia progression from 6 to 24 months.
In myopic children aged around 10 years in Taipei, longer distance in near work, discontinuing near work every 30 min and more outdoor time from parent self-report are protective behaviours in myopia prevalence and progression in 6-24 months.
Researchers of person–job (P‐J) misfit have suggested that newcomers who “misfit” with their job often perform poorly and eventually leave the organization. However, no known studies have examined ...ways to alleviate the negative impacts of newcomers’ P‐J misfit. Based on the theory of work adjustment and the spillover model of person–environment fit, we explore whether newcomers’ fit with the social context (i.e. person–group P‐G and person–organization P‐O fit) and interpersonal relationships (i.e. person–mentor P‐M and person–supervisor P‐S fit) can buffer the detrimental outcomes of newcomers’ P‐J misfit. Using data from two field studies with time‐lag and multi‐source research designs, the results consistently show that: (1) newcomers’ P‐G fit buffered the positive relationship between their initial N–S misfit and subsequent actual turnover, (2) newcomers’ P‐M fit buffered the negative relationship between their initial D‐A misfit and subsequent task performance. Theoretical and practical implications are also discussed.
Previous studies have confirmed that activity participation is beneficial to mental health, but few studies focus on older adults' depression. Based on the theory of social integration, this study ...examined the effects of leisure activity diversity and exercise time on depression in late adulthood. Subjects in the 2011 Survey of Health and Living Status of the Middle-Aged and Elderly in Taiwan were extracted. A series of logistic regressions were conducted to discern factors related to the odds of having depression. Among study subjects (
= 3727; age ≥ 58), 20.9% indicated an inclination of having depression (CESD-10 score ≥ 8). This study found that participating in diverse leisure activities and longer exercise time decreases older adults' risk of having depression. Additionally, the results confirmed that depression is positively correlated with chronic diseases. Consequently, efforts should be continually spent on encouraging older adults' participation in activities to reduce the prevalence of depression.
This study aimed to identify the spatial patterns of lower respiratory tract infections (LRIs) and their association with fine particulate matter (PM
). The disability-adjusted life year (DALY) ...database was used to represent the burden each country experiences as a result of LRIs. PM
data obtained from the Atmosphere Composition Analysis Group was assessed as the source for main exposure. Global Moran's I and Getis-Ord Gi* were applied to identify the spatial patterns and for hotspots analysis of LRIs. A generalized linear mixed model was coupled with a sensitivity test after controlling for covariates to estimate the association between LRIs and PM
. Subgroup analyses were performed to determine whether LRIs and PM
are correlated for various ages and geographic regions. A significant spatial auto-correlated pattern was identified for global LRIs with Moran's Index 0.79, and the hotspots of LRIs were clustered in 35 African and 4 Eastern Mediterranean countries. A consistent significant positive association between LRIs and PM
with a coefficient of 0.21 (95% CI 0.06-0.36) was identified. Furthermore, subgroup analysis revealed a significant effect of PM
on LRI for children (0-14 years) and the elderly (≥ 70 years), and this effect was confirmed to be significant in all regions except for those comprised of Eastern Mediterranean countries.
Classic signaling by the proinflammatory cytokine interleukin 6 (IL-6) involves its binding to target cells that express the membrane-bound IL-6 receptor α. However, an alternate signaling pathway ...exists in which soluble IL-6 receptor (sIL-6Rα) can bind IL-6 and activate target cells that lack mIL-6Rα, such as endothelial cells. This alternate pathway, also termed trans-signaling, serves as the major IL-6 signaling pathway in various pathologic proinflammatory conditions including cancer. Here we report that sIL-6Rα is elevated in malignant ascites from ovarian cancer patients, where it is associated with poor prognosis. IL-6 trans-signaling on endothelial cells prevented chemotherapy-induced apoptosis, induced endothelial hyperpermeability, and increased transendothelial migration of ovarian cancer cells. Selective blockade of the MAPK pathway with ERK inhibitor PD98059 reduced IL-6/sIL-6Rα-mediated endothelial hyperpermeability. ERK activation by the IL-6/sIL-6Rα complex increased endothelial integrity via Src kinase activation and Y685 phosphorylation of VE-cadherin. Selective targeting of IL-6 trans-signaling in vivo reduced ascites formation and enhanced the taxane sensitivity of intraperitoneal human ovarian tumor xenografts in mice. Collectively, our results show that increased levels of sIL-6Rα found in ovarian cancer ascites drive IL-6 trans-signaling on endothelial cells, thereby contributing to cancer progression. Selective blockade of IL-6 trans-signaling may offer a promising therapeutic strategy to improve the management of patients with advanced ovarian cancer.
Objectives
Early mortality, defined as death within 120 days after initiated antitumor therapy, is an important issue especially for elder patients with B‐cell lymphoma. This study aimed to evaluate ...the clinical value of comprehensive geriatric assessment (CGA) in early mortality prediction in elderly patients with B‐cell lymphoma receiving immunochemotherapy.
Methods
Seventy‐six consecutive patients with newly diagnosed B‐cell lymphoma receiving immunochemotherapy from a medical center in Taiwan were prospectively enrolled. Patients were divided into fit (n = 49) and frail (n = 27) groups per pretreatment CGA for early mortality comparison.
Results
The early mortality rate in our patient cohort was 16% (n = 12): from 6% in patients with no CGA domain impairment to 43% in patients with ≥4 CGA domain impairment. The early mortality rate was 6% and 33% in fit and frail patients (odds ratio, 7.67; 95% CI, 1.86‐31.6; P = .005), respectively. Frailty was the significant predictor for early mortality in univariate and multivariate analysis.
Conclusion
In this study, the number of geriatric domain impairment is positively associated with the early mortality risk in elderly patients with B‐cell lymphoma. Therefore, CGA can help clinicians to identify the risk of early mortality in elderly patients and provide alternative treatment.
Estimated glomerular filtration rate (eGFR) is used for diagnosis of chronic kidney disease (CKD). The eGFR models based on serum creatinine or cystatin C are used more in clinical practice. ...Albuminuria and neck circumference are associated with CKD and may have correlations with eGFR.
We explored the correlations and modelling formulates among various indicators such as serum creatinine, cystatin C, albuminuria, and neck circumference for eGFR.
Cross-sectional study.
We reviewed the records of patients with high cardiovascular risk from 2010 to 2011 in Taiwan. 24-hour urine creatinine clearance was used as the standard. We utilized a decision tree to select for variables and adopted a stepwise regression method to generate five models. Model 1 was based on only serum creatinine and was adjusted for age and gender. Model 2 added serum cystatin C, models 3 and 4 added albuminuria and neck circumference, respectively. Model 5 simultaneously added both albuminuria and neck circumference.
Total 177 patients were recruited in this study. In model 1, the bias was 2.01 and its precision was 14.04. In model 2, the bias was reduced to 1.86 with a precision of 13.48. The bias of model 3 was 1.49 with a precision of 12.89, and the bias for model 4 was 1.74 with a precision of 12.97. In model 5, the bias could be lower to 1.40 with a precision of 12.53.
In this study, the predicting ability of eGFR was improved after the addition of serum cystatin C compared to serum creatinine alone. The bias was more significantly reduced by the calculation of albuminuria. Furthermore, the model generated by combined albuminuria and neck circumference could provide the best eGFR predictions among these five eGFR models. Neck circumference can be investigated potentially in the further studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite advances in neuroscience, the mechanisms by which human brain resolve optical image formation through relational reasoning remain unclear, particularly its relationships with task difficulty. ...Therefore, this study explores the underlying brain dynamics involved in optical image formation tasks at various difficulty levels, including those with a single convex lens and a single mirror. Compared to single convex lens relational reasoning with high task difficulty, the single mirror relational reasoning exhibited significantly higher response accuracy and shorter latency. As compared to single mirror tasks, single convex tasks exhibited greater frontal midline theta augmentation and right parietal alpha suppression during phase I and earlier phase II, and augmentation of frontal midline theta, right parietal-occipital alpha, and left mu alpha suppression during late phase II. Moreover, the frontal midline theta power in late phase II predicts the likelihood of solving single convex tasks the best, while the parietal alpha power in phase I is most predictive. In addition, frontal midline theta power exhibited stronger synchronization with right parietal alpha, right occipital alpha, and mu alpha power when solving single convex tasks than single mirror tasks. In summary, having stronger brain dynamics and coordination is vital for achieving optical image formation with greater difficulty.
This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with ...hepatocellular carcinoma (HCC).
Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression.
Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL.
EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D.
NCT01970748.
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