Saffron (Crocus sativus L.) and health outcomes: a meta-research review of meta-analyses and an evidence mapping study

BackgroundAlthough a number of systematic reviews and meta-analyses of saffron (Crocus sativus L.) have been published, no study has comprehensively summarized the clinical evidence from meta-analyses, or assessed the reporting or methodological quality of these reviews.PurposeThe present meta-research study was designed to fill the gaps in knowledge to inform future studies and allow enhanced clinical decision-making on saffron.MethodsThe PubMed, Cochrane Library, Embase, and CNKI databases were systematically searched from inception to April 3 rd, 2021, for meta-analyses of clinical trials that assessed the efficacy and safety of saffron. PRISMA 2009 and AMSTAR-2 were employed to assess the reporting and methodological quality of meta-analyses identified in the search, respectively. The present study was registered on PROSPERO with registration number CRD42020220274.ResultsNineteen eligible systematic reviews with meta-analyses published in English were identified from 235 records. These meta-analyses were published in 12 peer-reviewed journals from 2013 to 2021. The heterogeneous results indicated that saffron significantly reduced fasting blood glucose, waist circumference, diastolic blood pressure, concentrations of total cholesterol and low-density lipoprotein cholesterol, and improved symptoms of depression, cognitive function and sexual dysfunction compared with controls (mainly placebos). Common side effects of saffron consumption included nausea, dry mouth, poor appetite, and headache, but no serious adverse reactions were reported. Primary analysis and sensitivity analysis confirmed that the reporting and methodological quality of reviews included in the study were highly correlated (p < 0.001). The quality of meta-analyses of saffron requires improvement by including a structured abstract, a prospective protocol and registration, explanation of the study designs within each study that is reviewed, the searches, risk of bias assessment, literature selection, and reporting of funding sources.ConclusionThe available evidence indicates that saffron is a safe plant for administration as a medicine and can improve diverse clinical outcomes, but the scientific quality of the published systematic reviews needs to be improved. Moreover, the clinical effects of saffron need to be confirmed through high-quality randomized trials in multiple countries with large sample sizes.     

Clinical implications of microRNAs in cancer

Abstract

MicroRNAs (miRNAs) are endogenously produced non-coding RNAs that serve as micromanagers by negatively regulating gene expression. MiRNAs are implicated in several biological pathways including development of neoplasia. Because altered miRNA expression is implicated in the pathobiology of various cancers, these molecules serve as potential therapeutic targets. Using miRNA mimics to restore levels of aberrantly down-regulated miRNAs or miRNA inhibitors to inactivate over-expressed miRNAs shows promise as the next generation of therapeutic strategies. Manipulation of miRNAs offers an alternative therapeutic approach for chemo- and radiation-resistant tumors. Similarly, miRNA expression patterns can be used for diagnosis and to predict prognosis and efficacy of therapy. We present here an overview of how miRNAs affect cancers, how they may be used as biomarkers, and the clinical implications of miRNAs in cancer.     

Prediction of global geographic distribution of Metcalfa pruinosa using CLIMEX

Globalization has changed the habitats of various species, resulting in harmful pest invasion. Among these pests, Metcalfa pruinosa has caused worldwide economic and hygienic damage in both urban and agricultural/forested areas. It has been reported that prediction of pest distribution is key to the management of pest prevention. Hence, this study aimed to predict the potential geographic distribution of M. pruinosa under the current climate and under a climate change scenario. CLIMEX, modeling software that analyzes the habitat suitability of a target species based on comprehensive climatic and physiological data, was used mainly to establish a map of predictive distribution of M. pruinosa at present and in the future. Based on our simulations, we predict that M. pruinosa will tend to extend its distribution northward in North America and Europe. We conclude that climate change could result in M. pruinosa invasion in a northward direction, suggesting the need for a thorough system of control and prevention.     

Bioavailability and dosing strategies of mineral in anaerobic mono‐digestion of maize straw

The influence of the bonding form distribution of Fe, Ni, Co and Mn and their potential bioavailability during the anaerobic degradation of maize straw was investigated. Two reactors were operated over 117 days at 37°C and different dosage strategies of mineral were studied in reactor (R2). Control reactor (R1) was metal‐limited over time. mineral supplementation (1 g L^?1) once a week reported the highest methane yield (257 mL g^?1 VS) with 30% of increment. Ni and Co predominated in their oxidizable bonding forms and Fe mainly existed as residual and oxidizable fractions. The potential bioavailability (Mn ?? Co ≈ Ni ? Fe) of R2 was higher comparing to R1. Metal deprivation in R1 led to depletion of both sequential extraction fractions and total metal concentrations until the end of the process. This study confirmed that the dosage strategy of mineral has a stimulatory effect on methane production from crop maize waste.     

Addressing an Idiosyncrasy in Estimating Survival Curves Using Double Sampling in the Presence of Self-Selected Right Censoring

We investigate the use of follow-up samples of individuals to estimate survival curves from studies that are subject to right censoring from two sources: (i) early termination of the study, namely, administrative censoring, or (ii) censoring due to lost data prior to administrative censoring, so-called dropout. We assume that, for the full cohort of individuals, administrative censoring times are independent of the subjects' inherent characteristics, including survival time. To address the loss to censoring due to dropout, which we allow to be possibly selective, we consider an intensive second phase of the study where a representative sample of the originally lost subjects is subsequently followed and their data recorded. As with double-sampling designs in survey methodology, the objective is to provide data on a representative subset of the dropouts. Despite assumed full response from the follow-up sample, we show that, in general in our setting, administrative censoring times are not independent of survival times within the two subgroups, nondropouts and sampled dropouts. As a result, the stratified Kaplan-Meier estimator is not appropriate for the cohort survival curve. Moreover, using the concept of potential outcomes, as opposed to observed outcomes, and thereby explicitly formulating the problem as a missing data problem, reveals and addresses these complications. We present an estimation method based on the likelihood of an easily observed subset of the data and study its properties analytically for large samples. We evaluate our method in a realistic situation by simulating data that match published margins on survival and dropout from an actual hip-replacement study. Limitations and extensions of our design and analytic method are discussed.     

Principal stratification designs to estimate input data missing due to death

We consider studies of cohorts of individuals after a critical event, such as an injury, with the following characteristics. First, the studies are designed to measure "input" variables, which describe the period before the critical event, and to characterize the distribution of the input variables in the cohort. Second, the studies are designed to measure "output" variables, primarily mortality after the critical event, and to characterize the predictive (conditional) distribution of mortality given the input variables in the cohort. Such studies often possess the complication that the input data are missing for those who die shortly after the critical event because the data collection takes place after the event. Standard methods of dealing with the missing inputs, such as imputation or weighting methods based on an assumption of ignorable missingness, are known to be generally invalid when the missingness of inputs is nonignorable, that is, when the distribution of the inputs is different between those who die and those who live. To address this issue, we propose a novel design that obtains and uses information on an additional key variable-a treatment or externally controlled variable, which if set at its "effective" level, could have prevented the death of those who died. We show that the new design can be used to draw valid inferences for the marginal distribution of inputs in the entire cohort, and for the conditional distribution of mortality given the inputs, also in the entire cohort, even under nonignorable missingness. The crucial framework that we use is principal stratification based on the potential outcomes, here mortality under both levels of treatment. We also show using illustrative preliminary injury data that our approach can reveal results that are more reasonable than the results of standard methods, in relatively dramatic ways. Thus, our approach suggests that the routine collection of data on variables that could be used as possible treatments in such studies of inputs and mortality should become common.     

Steady-state diffusion and the cell resting potential

The steady-state diffusion of ions through separate, selective channels is described according to irreversible thermodynamics. Ion fluxes thus obtained are the same as those in the parallel conductance model. The equivalent electric circuit set up to describe the system has its electromotive forces expressed by the chemical potentials of the diffusing ions. The expression obtained for the potential differs from the Goldman-Hodgkin-Katz formula, and is reputed to be more accurate. In order for the passive diffusion flows to remain steady, active transport mechanisms must pump the ions up their electrochemical potentials. Such pumps have been incorporated into the equivalent circuit. They supply energy lost in the dissipation caused by preexisting passive forces without affecting the potential, which can thus hardly be called passive diffusion potential. Ion pumps can also create an electric potential in excess of that by passive forces, especially when secondary active transport is involved. The same equivalent circuit is, however, able to describe the whole range of seemingly different situations – from passive diffusion of an electrolyte to active extrusion of anions from the living cell. It has been applied to explain the measured plasma membrane potential of cells, especially those whose potential does not behave as the potassium electrode. Received: 6 July 1998 / Revised version: 7 November 1998 / Accepted: 10 November 1998