MEPSA: Minimum energy pathway analysis for energy landscapes

From conformational studies to atomistic descriptions of enzymatic reactions, potential and free energy landscapes can be used to describe biomolecular systems in detail. However, extracting the relevant data of complex 3D energy surfaces can sometimes be laborious. In this article, we present MEPSA (Minimum Energy Path Surface Analysis), a cross-platform user friendly tool for the analysis of energy landscapes from a transition state theory perspective. Some of its most relevant features are: identification of all the barriers and minima of the landscape at once, description of maxima edge profiles, detection of the lowest energy path connecting two minima and generation of transition state theory diagrams along these paths. In addition to a built-in plotting system, MEPSA can save most of the generated data into easily parseable text files, allowing more versatile uses of MEPSA's output such as the generation of molecular dynamics restraints from a calculated path.Grant IPT2011-0964-900000 (Government of Spain).Peer Reviewe

Long-term Responders after autologous stem cell transplantation in multiple myeloma

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT. Methods: We retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as 'long-term responders' (LTRs). In the non-LTR group, a cohort referred to as 'prolonged responders' (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data. Results: Two hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up

FocusDET: Herramienta multimodal para la localización del foco epileptógeno en la epilepsia farmacorresistente

Los pacientes epilépticos con crisis parciales complejas resistentes a tratamiento farmacológico son candidatos a la escisión de la región focal del cerebro que induce dichas crisis. La correcta localización del foco epileptógeno es esencial para considerar la cirugía como posible tratamiento. El objetivo de este trabajo es el desarrollo de una aplicación médica para la localización del foco epileptógeno a partir de datos multimodales. Para el desarrollo de esta nueva herramienta se utiliza GIMIAS, una plataforma de software para la implementación y prototipado de aplicaciones médicas. La nueva herramienta desarrollada, FocusDET, permite llevar a cabo la técnica SISCOM y el análisis de datos EEG-RM f ictal, de imágenes PET y de distintas modalidades de imagen de RM. FocusDET, gracias a su interfaz amigable y a su rapidez de procesamiento, puede ser adecuada para la rutina clínica

Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery

This work was supported by the portfolio of translational research of the National Institutes for Health Research Cardiovascular Biomedical Research Unit at Barts, the UK Medical Research Council (JID-2015-0339), Major Research Plan of The National Natural Science Foundation of China [grant number U1435222], Plan for Innovative Graduate Student at NUDT [grant number B140202], Plan for interdisciplinary joint PhD students at NUDT and China Scholarship Council [to ZJ]