Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Facile Nanostructured Substrate Preparation Using Gold Nanocuboids for SERS

In the present work, we report a practical fabrication method of gold-aluminium substrates for surface en‐ hanced Raman spectroscopy. A commercial aluminium- foil was used to fabricate SERS substrates by depositing gold nanocuboids and faceted particles onto their surfaces using the drop-drying method. The gold nanoparticles were characterized by ultraviolet-visible spectroscopy, while the size and morphology were determined by field emission scanning electron microscopy. The perform‐ ance of the substrates was investigated using Rhoda‐ mine 6G in a water solution where a volume of 3 μl was placed on the surfaces of the SERS substrates, and the Raman spectra were immediately acquired using diode laser excitation at 785 nm. The estimated analytical enhancement factor of the gold-aluminium substrates was 1.8 x 106, using a solution of Rhodamine 6G with a concentration of 1 x 109 (0.4796 ppb). We show that our SERS substrates can be easily fabricated, and that they are reproducible and have suitable surface uniformity, thus allowing one to analyse Rhodamine 6G not only as a dry sample, but also in a solution

Large-Scale Continuous Flow Transformation of Oximes into Fused-Bicyclic Isoxazolidines: An Example of Process Intensification

Here, we report a continuous flow protocol for the [3 + 2] cycloaddition of nitrones, in situ generated from oximes, into bicyclic isoxazolidines. This thermal process required very high temperatures to be efficient that were not easily reached in conventional reactors. A couple of examples are presented and in both the flow process showed a greater performance than the batch mode. The process intensification study allowed the generation of 120 g/h of a key pharmaceutical intermediate

Alternating Current Electrokinetic Properties of Gold-Coated Microspheres

We present dielectrophoresis (DEP) and electrorotation (ROT) measurements of gold-coated polystyrene microspheres as a function of frequency and for several electrolyte conductivities. Particle rotation was counterfield with a maximum rotation rate observed at a single characteristic frequency. Negative DEP was observed for frequencies lower than this characteristic frequency and positive DEP for signal frequencies higher than this. These experimental observations are in agreement with predictions for the force and torque on the induced dipole of a perfectly polarizable metal sphere. We present a theoretical model for this case, and good agreement is found for both ROT and DEP measurements if we take into account the viscous friction for a spherical particle near a wall. From the characteristic frequency for rotation, we obtain the capacitance of the electrical double layer at the electrolyte–particle interface. Remarkably, no effect of induced charge electroosmosis around the particles can be inferred from DEP measurements

Quantitative Structure–Activity Relationships of Mosquito Larvicidal Chalcone Derivatives

The mosquito larvicidal activities of a series of chalcones and some derivatives were subjected to a quantitative structure–activity relationship (QSAR) study, using more than a thousand constitutional, topological, geometrical, and electronic molecular descriptors calculated with Dragon software. The larvicidal activity values for 28 active compounds of the series were predicted, showing in general a good approximation to the experimental values found in the literature. Chalcones having one or both electron-rich rings showed high toxicity. However, the activity of chalcones was reduced by electron-withdrawing groups, and this was roughly diminished by derivatization of the carbonyl group. A set of six chalcones being structurally similar to some of the active ones, with a still unknown larvicidal activity, were prepared. Their activity values were predicted by applying the developed QSAR models, showing that two chalcones of such set, both <b>32</b> and <b>34</b>, were expected to be highly active

Proteogenomics Dashboard for the Human Proteome Project

<i>dasHPPboard</i> is a novel proteomics-based dashboard that collects and reports the experiments produced by the Spanish Human Proteome Project consortium (SpHPP) and aims to help HPP to map the entire human proteome. We have followed the strategy of analog genomics projects like the Encyclopedia of DNA Elements (ENCODE), which provides a vast amount of data on human cell lines experiments. The dashboard includes results of shotgun and selected reaction monitoring proteomics experiments, post-translational modifications information, as well as proteogenomics studies. We have also processed the transcriptomics data from the ENCODE and Human Body Map (HBM) projects for the identification of specific gene expression patterns in different cell lines and tissues, taking special interest in those genes having little proteomic evidence available (missing proteins). Peptide databases have been built using single nucleotide variants and novel junctions derived from RNA-Seq data that can be used in search engines for sample-specific protein identifications on the same cell lines or tissues. The <i>dasHPPboard</i> has been designed as a tool that can be used to share and visualize a combination of proteomic and transcriptomic data, providing at the same time easy access to resources for proteogenomics analyses. The <i>dasHPPboard</i> can be freely accessed at: http://sphppdashboard.cnb.csic.es