Leveraging Social Media for Cardio-Oncology.

OPINION STATEMENT: As the world becomes more connected through online and offline social networking, there has been much discussion of how the rapid rise of social media could be used in ways that can be productive and instructive in various healthcare specialties, such as Cardiology and its subspecialty areas. In this review, the role of social media in the field of Cardio-Oncology is discussed. With an estimated 17 million cancer survivors in the USA in 2019 and 22 million estimated by 2030, more education and awareness are needed. Networking and collaboration are also needed to meet the needs of our patients and healthcare professionals in this emerging field bridging two disciplines. Cardiovascular disease is second only to recurrence of the primary cancer or diagnosis with a secondary malignancy, as a leading cause of death in cancer survivors. A majority of these survivors are anticipated to be on social media seeking information, support, and ideas for optimizing health. Healthcare professionals in Cardio-Oncology are also online for networking, education, scholarship, career development, and advocacy in this field. Here, we describe the utilization and potential impact of social media in Cardio-Oncology, with inclusion of various hashtags frequently used in the Cardio-Oncology Twitter community.

Communication: Stiff and soft nano-environments and the "Octopus Effect" are the crux of ionic liquid structural and dynamical heterogeneity.

In a recent set of articles [J. C. Araque et al., J. Phys. Chem. B 119(23), 7015-7029 (2015) and J. C. Araque et al., J. Chem. Phys. 144, 204504 (2016)], we proposed the idea that for small neutral and charged solutes dissolved in ionic liquids, deviation from simple hydrodynamic predictions in translational and rotational dynamics can be explained in terms of diffusion through nano-environments that are stiff (high electrostriction, charge density, and number density) and others that are soft (charge depleted). The current article takes a purely solvent-centric approach in trying to provide molecular detail and intuitive visual understanding of time-dependent local mobility focusing on the most common case of an ionic liquid with well defined polar and apolar nano-domains. We find that at intermediate time scales, apolar regions are fluid, whereas the charge network is much less mobile. Because apolar domains and cationic heads must diffuse as single species, at long time the difference in mobility also necessarily dissipates.

A link between structure, diffusion and rotations of hydrogen bonding tracers in ionic liquids.

When solutes are small compared to the size of the ions in an ionic liquid, energetic heterogeneities associated with charge enhanced (stiff) and charge depleted (soft) nanoenvironments are sampled. In a recent article [J. C. Araque et al., J. Phys. Chem. B 119(23), 7015-7029 (2015)], we explored large deviations from Stokes-Einstein translational diffusion caused by such a heterogeneity. The current article is set to explore the effect of soft and stiff solvent environments (i.e., structure) on OH-bond rotations in the case of water and small alcohols in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (Im1,2 (+)NTf2 (-)). Is solute rotational dynamics heterogeneous? If so, are solute rotations and translations coupled in the sense that stiff and soft solvent environments hinder or speed up both types of dynamics? For the systems studied here, there appears to be a clear connection between translations, rotations, and stiff/soft solvent environments. We also discuss interesting asymmetries of the correlation between solutes with anions and cations.

How does the ionic liquid organizational landscape change when nonpolar cationic alkyl groups are replaced by polar isoelectronic diethers?

X-ray scattering experiments and molecular dynamics simulations have been performed to investigate the structure of four room temperature ionic liquids (ILs) comprising the bis(trifluoromethylsulfonyl)amide (NTf(2)(-)) anion paired with the triethyloctylammonium (N(2228)(+)) and triethyloctylphosphonium (P(2228)(+)) cations and their isoelectronic diether analogs, the (2-ethoxyethoxy)ethyltriethylammonium (N(222(2O2O2))(+)) and (2-ethoxyethoxy)ethyltriethylphosphonium (P(222(2O2O2))(+)) cations. Agreement between simulations and experiments is good and permits a clear interpretation of the important topological differences between these systems. The first sharp diffraction peak (or prepeak) in the structure function S(q) that is present in the case of the liquids containing the alkyl-substituted cations is absent in the case of the diether substituted analogs. Using different theoretical partitioning schemes for the X-ray structure function, we show that the prepeak present in the alkyl-substituted ILs arises from polarity alternations between charged groups and nonpolar alkyl tails. In the case of the diether substituted ILs, we find considerable curling of tails. Anions can be found with high probability in two different environments: close to the cationic nitrogen (phosphorus) and also close to the two ether groups. For the two diether systems, anions are found in locations from which they are excluded in the alkyl-substituted systems. This removes the longer range (polar/nonpolar) pattern of alternation that gives rise to the prepeak in alkyl-substituted systems.

Sugar Folding: A Novel Structural Prediction Tool for Oligosaccharides and Polysaccharides 2.

This is the second in a set of two articles where we describe our newly developed scheme to predict conformations of complex oligosaccharides in solution. We apply our fast sugar conformation prediction tool to the case of two complex human milk oligosaccharides LNF-1 and LND-1. As described in detail in the first paper, our protocol initially delivers a set of "unique structures" corresponding to important minima on the potential-energy landscape of a complex sugar using an implicit solvent model. The nuclear Overhauser effect ranking of individual conformations provides a suitable way for comparison with available experiments. The structures obtained agree well with earlier computational predictions but are obtained at a significantly lower computational cost. Sugar conformations corresponding to stable energy minima not found by earlier molecular dynamics studies were also detected using our methodology. In order to evaluate the effects of explicit solvation and thermal fluctuations on several different predicted conformers, we also performed short-time molecular dynamics simulations in an explicit solvent.

Sugar Folding: A Novel Structural Prediction Tool for Oligosaccharides and Polysaccharides 1.

This paper is the first in a series of two articles where we report the development of fast sugar structure prediction software (FSPS). To the best of our knowledge, this is the first automated tool for the systematic study of conformations of complex oligosaccharides in solution. In contrast to previously developed molecular builders such as POLYS (Engelsen, S. B.; Cros, S.; Mackie, W.; Perez, S. Biopolymers 1996, 39, 417-433) where only information about the minimum energy conformation of disaccharide pairs is considered in order to build larger oligosaccharides, this tool is based on a systematic search of dihedral conformational space, optimization of structures using implicit solvation models, explicit molecular dynamics simulations, NOE calculations, and a very powerful substructure recognition algorithm and database. Our FSPS can rapidly find minimum-energy conformers and rank them according to different criteria. Two such criteria are the energy of the conformers in implicit solvent and the root-mean-square deviation (RMSD) of computed NOEs with respect to experimental data. Even though experimental NOEs may result from an average over conformers instead of a single structure, we find that sorting according to NOE RMSD constitutes a better estimator for the global free-energy minimum structure in explicit solvent (i.e., the most likely structure in solution). In contrast, the lowest-energy structure in implicit solvent does not usually correspond to the free-energy minimum. A harmonic approximation to compute free energies of each conformer does not appear to reverse this conclusion, indicating that either explicit hydrogen bonding to the solvent or anharmonic effects in the free energy or both are fundamentally important. In the first article, we discuss our methodology and study, as a proof of concept, a simple substituted disaccharide. In the second article, we focus on two complex human milk oligosaccharides.