Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Diagnostic accuracy of the primary care screener for affective disorder (PC-SAD) in primary care

Background: Depression goes often unrecognised and untreated in non-psychiatric medical settings. Screening has recently gained acceptance as a first step towards improving depression recognition and management. The Primary Care Screener for Affective Disorders (PC-SAD) is a self-administered questionnaire to screen for Major Depressive Disorder (MDD) and Dysthymic Disorder (Dys) which has a sophisticated scoring algorithm that confers several advantages. This study tested its performance against a ‘gold standard’ diagnostic interview in primary care. Methods: A total of 416 adults attending 13 urban general internal medicine primary care practices completed the PC-SAD. Of 409 who returned a valid PC-SAD, all those scoring positive (N=151) and a random sample (N=106) of those scoring negative were selected for a 3-month telephone follow-up assessment including the administration of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) by a psychiatrist who was masked to PC-SAD results. Results: Most selected patients (N=212) took part in the follow-up assessment. After adjustment for partial verification bias the sensitivity, specificity, positive and negative predictive value for MDD were 90%, 83%, 51%, and 98%. For Dys, the corresponding figures were 78%, 79%, 8%, and 88%. Conclusions: While some study limitations suggest caution in interpreting our results, this study corroborated the diagnostic validity of the PC-SAD, although the low PPV may limit its usefulness with regard to Dys. Given its good psychometric properties and the short average administration time, the PC-SAD might be the screening instrument of choice in settings where the technology for computer automated scoring is available

Is simulation the only keystone of surgical training?

No abstract availabl

What trans-vaginal ultrasound parameters are better correlated with a shorter labor induction to vaginal delivery interval? A prospective observational cohort study

Objective: During the induction of labor (IOL) planning, it is important to provide patients with information regarding how long the induction process might take. This study aimed to determine which ultrasonographic cervical parameters are independently associated with a shorter IOL-to-vaginal delivery (VD) interval. Methods: This was a prospective observational cohort study. For enrollment purposes, women with single pregnancy, fetus in cephalic presentation, age between 18 and 45 years and good Italian proficiency were included. Women with a history of uterine surgery, in active labor, and cases of fetal growth abnormalities were excluded. The enrolled women underwent a transvaginal ultrasound within 7 days from the scheduled labor induction in order to measure the following parameters: the cervical length (CL), the utero-cervical angle (UCA), the cervical sliding sign (CSS) and the cervical consistency index (CCI). Before starting the labor induction process, patients were also digitally evaluated, acquiring the Bishop score (BS). The method of IOL was determined based on the BS. Ultrasound assessments and Bishop score evaluations were performed independently and in a blinded manner to reduce bias. Statistical analyses were performed using STATA 18.0. Results: Between June 2023 and November 2024, 400 women were nonconsecutively enrolled in the study. Of these, 83 experienced spontaneous labor before the scheduled labor induction, resulting in 317 women who underwent IOL. The median IOL-to-VD interval was 1264 min (IQR 694–1940). Univariable regression analysis demonstrated significant associations between the IOL-to-VD interval and CL (β = 29.15; 95% CI 16.16, 42.23; p < 0.001), CCI (β = 12.60; 95% CI 3.93, 21.24; p = 0.004), and BS (β = −211.15; 95% CI −271.59, −150.71; p < 0.001). Multivariable analysis confirmed independent associations with CL (β = 13.89; 95% CI 0.35,27.44; p = 0.044) and BS (β = −183.96; −249.66, −118.27; p < 0.001). When stratified by parity, univariable regression in parous women showed significant associations between the IOL-to-VD interval and CL (β = 37.44; 95% CI 20.17, 54.72; p < 0.001), CSS (β = −582; 95% CI −1014.05, 151.20; p = 0.009), CCI (β = 15.43; 95% CI 1.75, 29.11; p = 0.027), and BS (β = −227.96; −315.57, −140.35; p < 0.001). Conclusions: In summary, among the evaluated parameters, CL consistently showed the strongest and most independent association with a shorter IOL-to-VD interval across analyses, supporting its role as the most reliable predictor. Future research should explore multivariable prediction models incorporating various ultrasonographic cervical parameters to enhance the predictive accuracy of transvaginal ultrasound

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes

The value of remote marine aerosol measurements for constraining radiative forcing uncertainty

Aerosol measurements over the Southern Ocean are used to constrain aerosol–cloud interaction radiative forcing (RFaci) uncertainty in a global climate model. Forcing uncertainty is quantified using 1 million climate model variants that sample the uncertainty in nearly 30 model parameters. Measurements of cloud condensation nuclei and other aerosol properties from an Antarctic circumnavigation expedition strongly constrain natural aerosol emissions: default sea spray emissions need to be increased by around a factor of 3 to be consistent with measurements. Forcing uncertainty is reduced by around 7 % using this set of several hundred measurements, which is comparable to the 8 % reduction achieved using a diverse and extensive set of over 9000 predominantly Northern Hemisphere measurements. When Southern Ocean and Northern Hemisphere measurements are combined, uncertainty in RFaci is reduced by 21 %, and the strongest 20 % of forcing values are ruled out as implausible. In this combined constraint, observationally plausible RFaci is around 0.17 W m−2 weaker (less negative) with 95 % credible values ranging from −2.51 to −1.17 W m−2 (standard deviation of −2.18 to −1.46 W m−2). The Southern Ocean and Northern Hemisphere measurement datasets are complementary because they constrain different processes. These results highlight the value of remote marine aerosol measurements