Search

Signal Amplification by Reversible Exchange (SABRE) is a relatively simple and fast hyperpolarization technique that has been used to hyperpolarize the α-ketocarboxylate pyruvate, a central metabolite and the leading hyperpolarized MRI contrast agent. In this work, we show that SABRE can readily be extended to hyperpolarize 13C nuclei at natural abundance on many other α-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P13C=17%) and 2-oxobutyrate (P13C=25%) with alkyl chains in the R-group, oxaloacetate (P13C=11%) and alpha-ketoglutarate (P13C=13%) with carboxylate moieties in the R group, and phenylpyruvate (P13C=2%) and phenylglyoxylate (P13C=2%) with phenyl rings in the R-group. New catalytically active SABRE binding motifs of the substrates to the hyperpolarization transfer catalyst-particularly for oxaloacetate-are observed. We experimentally explore the connection between temperature and exchange rates for all of these SABRE systems and develop a theoretical kinetic model, which is used to fit the hyperpolarization build-up and decay during SABRE activity., (© 2024 Wiley‐VCH GmbH.)

This study examined day-level associations between trouble sleeping and three cannabis-use indices (likelihood/quantity of use and impaired control). We evaluated behavioral and cognitive mediators of the association between trouble sleeping and cannabis outcomes. Youth ( N = 86, ages 15-24, 48.8% female, 58.8% White, 18.6% Latine) who regularly used cannabis were recruited for an intervention study. This preregistered secondary data analysis leveraged data from a 1-week ecological momentary assessment (EMA) study completed prior to intervention. Trouble sleeping, cannabis use, and impaired control over use were assessed each morning; negative affect, risk-taking propensity, and cannabis craving were assessed multiple times and aggregated to create a daily average. Multilevel structural equation modeling evaluated hypothesized temporally sequenced associations and putative mechanisms at the day (i.e., within) and person (i.e., between) level. In bivariate analyses at the person level, there were large-effect associations between trouble sleeping and craving and negative affect, and between craving and cannabis-use likelihood and quantity (rs from .34 to .48). In multilevel analyses at the day level, participants were less likely to use cannabis the next day after reporting more trouble sleeping (β = -.65, p < .001). Trouble sleeping was not directly associated with subsequent cannabis-use quantity or impaired control, or indirectly via negative affect, risk-taking propensity, or craving. Trouble sleeping had differential relations with cannabis-use indices at the day and person levels. To promote youth health and reduce cannabis use, future research may consider the unique, person- and situation-driven mechanistic processes at play. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Endometrial cancer (EC) is the only gynecologic malignancy showing increasing trends in incidence and mortality. While standard treatment has been effective primarily for early-stage EC, precision medicine with tailored therapy has revolutionized the management of this disease. Genome sequencing analyses have identified four sub-types of EC. Treatments for primary and metastatic disease can now be tailored more accurately to achieve better oncologic results., Areas Covered: This review provides an overview of the most relevant and updated evidence in the literature regarding EC molecular analysis and its role in risk classification, prognostication, and guidance for tailored and target therapies in early and advanced/metastatic stages. In addition, it provides updated information on optimal surgical management based on molecular classification and highlights key advances and future strategies., Expert Opinion: EC molecular analysis yields the potential of tailoring adjuvant treatment by escalating or deescalating therapy, as shown for POLE-mutated and p53-mutated tumors. Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.