Precautions to Consider in the Analysis of Prognostic and Predictive Indices.

Understanding the differences between prognostic and predictive indices is imperative for medical research advances. We have developed a new prognostic measure that will identify the strengths, limitations, and potential applications in clinical practice.

Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients.

A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the "REal world dAta in LYmphoma and survival in adults" (REALYSA) cohort.

Background: Age-adjusted lymphoma incidence rates continue to rise in France since the early 80's, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e.

Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells.

Background: Many cancers show aberrant silencing of gene expression and overexpression of histone methyltransferases. The histone methyltransferases (HKMT) EZH2 and EHMT2 maintain the repressive chromatin histone methylation marks H3K27me and H3K9me, respectively, which are associated with transcriptional silencing. Although selective HKMT inhibitors reduce levels of individual repressive marks, removal of H3K27me3 by specific EZH2 inhibitors, for instance, may not be sufficient for inducing the expression of genes with multiple repressive marks.

Chiroptical studies on brevianamide B: vibrational and electronic circular dichroism confronted.

Chiroptical spectroscopies, such as electronic circular dichroism (ECD) and vibrational circular dichroism (VCD), are highly sensitive techniques to probe molecular conformation, configuration, solvation, and aggregation. Here we report the application of these techniques to study the fungal metabolite brevianamide B. Comparison of the experimental ECD and VCD spectra with the density functional theory simulated counterparts establishes that VCD is the more reliable technique to assign absolute configuration due to the larger functional and dispersion dependence of computed ECD spectra.

On the histone lysine methyltransferase activity of fungal metabolite chaetocin.

Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally related analogues.

Mechanistic and chiroptical studies on the desulfurization of epidithiodioxopiperazines reveal universal retention of configuration at the bridgehead carbon atoms.

The stereochemistry of the desulfurization products of chiral natural and synthetic 3,6-epidithiodiketopiperazines (ETPs) is specified inconsistently in the literature. Qualitative mechanisms have been put forward to explain apparently divergent stereochemical pathways, but the quantitative feasibility of such mechanistic pathways has not been assessed. We report a computational study revealing that desulfurization of ETPs should occur universally with retention of configuration.

Experimental analysis of the transverse mechanical behaviour of annulus fibrosus tissue.

Uniaxial tensile and relaxation tests were carried out on annulus fibrosus samples carved out in the circumferential direction. Images were shot perpendicularly to the loading direction. Digital image correlation techniques accurately measured the evolution of full displacement fields in both transverse directions: plane of fibres and plane of lamellae.

Perspectives on natural product epigenetic modulators in chemical biology and medicine.

Epigenetic processes are complex regulatory transcriptional pathways that underpin fundamental physiology and are implicated in the aetiology of many diseases. Small molecule modulators of key epigenetic targets will be central in the study of these intricate networks as well as providing highly useful start points for drug discovery efforts. In this review we will give our perspective on the current status of natural product epigenetic modulators, highlighting the limitations, challenges and opportunities for currently identified molecules, as well as potential strategies for novel compound discovery moving forward.

Current limitations and future opportunities for epigenetic therapies.

This article reviews progress in epigenetic therapies that hope to improve the treatment of cancer. Tumors show widespread, aberrant epigenetic changes, leading to changes in the expression of genes involved in all the hallmarks of cancer. These epigenetic changes can potentially be reversed using small-molecule inhibitors of enzymes involved in maintenance of the epigenetic state.

On the determination of the stereochemistry of semisynthetic natural product analogues using chiroptical spectroscopy: desulfurization of epidithiodioxopiperazine fungal metabolites.

Isolation and semisynthetic modification of the fungal metabolite chaetocin gave access to a desulfurized analogue of this natural product. Detailed chiroptical studies, comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to computationally simulated ones, reveal the desulfurization of chaetocin to unambiguously proceed with retention of configuration. Consideration of the plausible mechanisms for this process highlighted inconsistencies in the stereochemical assignment of related molecules in the literature.

A new experimental method to determine the sorption isotherm of a liquid in a porous medium.

Sorption from the vapor phase is an important factor controlling the transport of volatile organic compounds (VOCs) in the vadose zone. Therefore, an accurate description of sorption behavior is essential to predict the ultimate fate of contaminants. Several measurement techniques are available in the case of water, however, when dealing with VOCs, the determination of sorption characteristics generally relies on gas chromatography.

Mechanical behavior of annulus fibrosus: a microstructural model of fibers reorientation.

Experimental uniaxial tensile tests have been carried out on annulus tissue samples harvested on pig and lamb lumbar intervertebral discs. When subjecting the samples to loading cycles, the stress-strain curves exhibit strong nonlinearities and hysteresis. This particular behavior results from the anisotropic microstructure of annulus tissue composed of woven oriented collagen fibers embedded in the extracellular matrix.

Capillary cohesion and mechanical strength of polydisperse granular materials.

We investigate the macroscopic mechanical behaviour of wet polydisperse granular media. Capillary bonding between two grains of unequal diameters is described by a realistic force law implemented in a molecular-dynamics algorithm together with a protocol for the distribution of water in the bulk. Axial-compression tests are simulated for granular samples at different levels of water content, and compared to experiments performed in similar conditions.