Plasma glycosaminoglycan scores in early stage renal cell carcinoma

Introduction & Objectives No diagnostic blood biomarker for RCC is currently used in the clinical routine. Using a systems biology approach, we previously developed a score based on circulating glycosaminoglycans (GAGs) that detected metastatic clear cell renal cell carcinoma (RCC) with 92.6%, 93.7%, and 100% accuracy vs. healthy subjects using either plasma, urine, or combined measurements in a validation cohort (Gatto et al., 2016, Cell Reports). It is still unknown if this test is accurate in early stage RCC or other RCC histologies. The primary endpoint of this study was the area-under-thecurve (AUC) in the use of plasma GAG scores to detect pre-operative RCC, any stage and any histology, versus healthy individuals

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes. insights from the CLIMA study

Purpose: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. Methods: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. Results: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p <0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p =0.019), lower macrophage infiltration (p <0.001) and intra-plaque layered tissue (p =0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (>67 degrees) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p =0.018) and a small minimum lumen area (HR 4.97, p =0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180 degrees) was associated with AEs in men (HR 2.56, p =0.003) but not in women. Conclusion: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies

Electroweak parameters of the z0 resonance and the standard model

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Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes

Enzymic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chem. and in biol.  Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts.  To address this, we show that incorporation of a d6-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis.  To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades.  Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase (HRP)-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine, and (iv) regeneration of NADH to promote a monooxygenase-catalyzed oxyfunctionalization reactio