Eastern Spanish experience with nivolumab in metastatic renal cell carcinoma.

BACKGROUND (OR PURPOSE): Nivolumab has been shown to be effective for the treatment of second-line mRCC. The present study has investigated the effectiveness and safety of nivolumab in real-world Eastern Spanish patients with advanced mRCC at TKI progression. PATIENTS AND METHODS: A retrospective review of mRCC patients treated with nivolumab as a second-line treatment was performed. Analyzed variables included age, sex, ECOG (quality of life scale designed by the Eastern Cooperative Oncology Group), histology, nephrectomy, location of metastases, number of metastasis locations, previous treatments, analytical data from the standard blood count and biochemistry, and response to treatment. RESULTS: 98 patients from 18 sites in Spain were retrospectively reviewed. The majority of patients were male (75%), had ECOG 0-1 (90.6%), had no brain metastasis (91.4%), had undergone one prior systemic regimen (94.3%), and were current/former smokers (97.1%). Fourteen patients (13.1%) had non-clear cell histology, seven (7.1%) had poor-IMDC prognostic group characteristics, 13 patients (13.1%) had liver metastasis and 35 (35.7%) had bone lesions. All patients received prior systemic therapy (63.3% sunitinib, 34.7% pazopanib). During the study, a median of eight doses of nivolumab was given (range 2-62) and 11 patients received more than 12 doses. Eleven patients (11.2%) received nivolumab as a third or fourth line of treatment. Median duration of therapy was 3.6 months (range 0.5-29.3). Confirmed response rate was 25%. Median progression free survival was 7.8 months (range 1.2-12.1). Median overall survival was 16.3 months (range 1.7-29.3). After discontinuation of treatment, 27.58% of the patients received subsequent systemic cancer therapy. Side effects were mostly grade 1-2 (7.2% had hypothyroidism and 6.2% liver toxicity, 4% had nephritis and 2% hypophysitis). Two cases of grade 3-4 adverse events (2%) were reported. CONCLUSION: Benefit/risk profile of nivolumab in Eastern-Spanish real-world population with mRCC after tyrosine-kinase inhibitors was consistent with prior real-life studies reported as well as pivotal study.

13Check_RNA: a tool to evaluate 13C chemical shift assignments of RNA.

Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.

Finite Dimension: A Mathematical Tool to Analise Glycans.

There is a need to develop widely applicable tools to understand glycan organization, diversity and structure. We present a graph-theoretical study of a large sample of glycans in terms of finite dimension, a new metric which is an adaptation to finite sets of the classical Hausdorff "fractal" dimension. Every glycan in the sample is encoded, via finite dimension, as a point of Glycan Space, a new notion introduced in this paper. Two major outcomes were found: (a) the existence of universal bounds that restrict the universe of possible glycans and show, for instance, that the graphs of glycans are a very special type of chemical graph, and (b) how Glycan Space is related to biological domains associated to the analysed glycans. In addition, we discuss briefly how this encoding may help to improve search in glycan databases.

Electrostatic unfolding and interactions of albumin driven by pH changes: a molecular dynamics study.

A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.