Multiplicative models for survival percentiles: estimating percentile ratios and multiplicative interaction in the metric of time

Evaluating percentiles of survival was proposed as a possible method to analyze time-to-event outcomes. This approach sets the cumulative risk of the event of interest to a specific proportion and evaluates the time by which this proportion is attainedIn this context, exposure-outcome associations can be expressed in terms of differences in survival percentiles, expressing the difference in survival time by which different subgroups of the study population experience the same proportion of events, or in terms of percentile ratios, expressing the strength of the exposure in accelerating the time to the event. Additive models for conditional survival percentiles have been introduced, and their use to estimate multivariable-adjusted percentile differences, and additive interaction on the metric of time has been described. On the other hand, the percentile ratio has never been fully described, neither statistical methods have been presented for its models-based estimation. To bridge this gap, we provide a detailed presentation of the percentile ratio as a relative measure to assess exposure-outcome associations in the context of time-to-event analysis, discussing its interpretation and advantages. We then introduce multiplicative statistical models for conditional survival percentiles, and present their use in estimating percentile ratios and multiplicative interactions in the metric of time. The introduction of multiplicative models for survival percentiles allows researchers to apply this approach in a large variety of context where multivariable adjustment is required, enriching the potentials of the percentile approach as a flexible and valuable tool to evaluate time-to-event outcomes in medical research

Splice-mediated Variants of Proteins (SpliVaP) – data and characterization of changes in signatures among protein isoforms due to alternative splicing

<p>Abstract</p> <p>Background</p> <p>It is often the case that mammalian genes are alternatively spliced; the resulting alternate transcripts often encode protein isoforms that differ in amino acid sequences. Changes among the protein isoforms can alter the cellular properties of proteins. The effect can range from a subtle modulation to a complete loss of function.</p> <p>Results</p> <p>(i) We examined human splice-mediated protein isoforms (as extracted from a manually curated data set, and from a computationally predicted data set) for differences in the annotation for protein signatures (Pfam domains and PRINTS fingerprints) and we characterized the differences & their effects on protein functionalities. An important question addressed relates to the extent of protein isoforms that may lack any known function in the cell. (ii) We present a database that reports differences in protein signatures among human splice-mediated protein isoform sequences.</p> <p>Conclusion</p> <p>(i) Characterization: The work points to distinct sets of alternatively spliced genes with varying degrees of annotation for the splice-mediated protein isoforms. Protein molecular functions seen to be often affected are those that relate to: binding, catalytic, transcription regulation, structural molecule, transporter, motor, and antioxidant; and the processes that are often affected are nucleic acid binding, signal transduction, and protein-protein interactions. Signatures are often included/excluded and truncated in length among protein isoforms; truncation is seen as the predominant type of change. Analysis points to the following novel aspects: (a) Analysis using data from the manually curated Vega indicates that one in 8.9 genes can lead to a protein isoform of no "known" function; and one in 18 expressed protein isoforms can be such an "orphan" isoform; the corresponding numbers as seen with computationally predicted ASD data set are: one in 4.9 genes and one in 9.8 isoforms. (b) When swapping of signatures occurs, it is often between those of same functional classifications. (c) Pfam domains can occur in varying lengths, and PRINTS fingerprints can occur with varying number of constituent motifs among isoforms – since such a variation is seen in large number of genes, it could be a general mechanism to modulate protein function. (ii) Data: The reported resource (at <url>http://www.bioinformatica.crs4.org/tools/dbs/splivap/</url>) provides the community ability to access data on splice-mediated protein isoforms (with value-added annotation such as association with diseases) through changes in protein signatures.</p

Usable Security. A Systematic Literature Review

Usable security involves designing security measures that accommodate users’ needs and behaviors. Balancing usability and security poses challenges: the more secure the systems, the less usable they will be. On the contrary, more usable systems will be less secure. Numerous studies have addressed this balance. These studies, spanning psychology and computer science/engineering, contribute diverse perspectives, necessitating a systematic review to understand strategies and findings in this area. This systematic literature review examined articles on usable security from 2005 to 2022. A total of 55 research studies were selected after evaluation. The studies have been broadly categorized into four main clusters, each addressing different aspects: (1) usability of authentication methods, (2) helping security developers improve usability, (3) design strategies for influencing user security behavior, and (4) formal models for usable security evaluation. Based on this review, we report that the field’s current state reveals a certain immaturity, with studies tending toward system comparisons rather than establishing robust design guidelines based on a thorough analysis of user behavior. A common theoretical and methodological background is one of the main areas for improvement in this area of research. Moreover, the absence of requirements for Usable security in almost all development contexts greatly discourages implementing good practices since the earlier stages of development

Correlates of total physical activity among middle-aged and elderly women

Information on correlates of total physical activity (PA) levels among middle-aged and elderly women is limited. This article aims to investigate whether total daily PA levels are associated with age, body mass index, smoking, drinking status, and sociodemographic factors

The MEPS server for identifying protein conformational epitopes

<p>Abstract</p> <p>Background</p> <p>One of the most interesting problems in molecular immunology is epitope mapping, i.e. the identification of the regions of interaction between an antigen and an antibody. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues involved in the interaction and could be instrumental both in designing peptides able to mimic the interacting surface of the antigen and in understanding where immunologically important regions are located in its three-dimensional structure. From an experimental point of view, both genetically encoded and chemically synthesised peptide libraries can be used to identify sequences recognized by a given antibody. The problem then arises of which region of a folded protein the selected peptides correspond to.</p> <p>Results</p> <p>We have developed a method able to find the surface region of a protein that can be effectively mimicked by a peptide, given the structure of the protein and the maximum number of side chains deemed to be required for recognition. The method is implemented as a publicly available server. It can also find and report all peptide sequences of a specified length that can mimic the surface of a given protein and store them in a database.</p> <p>The immediate application of the server is the mapping of antibody epitopes, however the system is sufficiently flexible for allowing other questions to be asked, for example one can compare the peptides representing the surface of two proteins known to interact with the same macromolecule to find which is the most likely interacting region.</p> <p>Conclusion</p> <p>We believe that the MEPS server, available at <url>http://www.caspur.it/meps</url>, will be a useful tool for immunologists and structural and computational biologists. We plan to use it ourselves to implement a database of "surface mimicking peptides" for all proteins of known structure and proteins that can be reliably modelled by comparative modelling.</p

MAISTAS: a tool for automatic structural evaluation of alternative splicing products

Motivation: Analysis of the human genome revealed that the amount of transcribed sequence is an order of magnitude greater than the number of predicted and well-characterized genes. A sizeable fraction of these transcripts is related to alternatively spliced forms of known protein coding genes. Inspection of the alternatively spliced transcripts identified in the pilot phase of the ENCODE project has clearly shown that often their structure might substantially differ from that of other isoforms of the same gene, and therefore that they might perform unrelated functions, or that they might even not correspond to a functional protein. Identifying these cases is obviously relevant for the functional assignment of gene products and for the interpretation of the effect of variations in the corresponding proteins

The State of Organic Seed in Europe

This booklet aims at supporting the expansion, both horizontal and vertical, of the European market for organic seed. Organic farmers need seed bred specifically to withstand the local and environmental conditions without the use of external, synthetic inputs. The size of the demand, however, does not justify the investment needed, when left entirely to market forces. This booklet estimates the potential market for organic seed in the EU and any challenges to its full development, and particularly the role played by the current derogation process for use of conventional untreated seed. Also analysed is the lack and inconsistency of information for farmers on what is available and how it meets their needs. In particular, the study compares and identifies gaps in the use of national databases and annual reports on derogations across Europe, and how these can be modified to provide stronger policy incentives to the market. Suppliers were interviewed on technical and economic challenges to seed production and farmers were involved in discussions on how organic seed is acquired and used

The State of Organic Seed in Europe

This booklet aims at supporting the expansion, both horizontal and vertical, of the European market for organic seed. Organic farmers need seed bred specifically to withstand the local and environmental conditions without the use of external, synthetic inputs. The size of the demand, however, does not justify the investment needed, when left entirely to market forces. This booklet estimates the potential market for organic seed in the EU and any challenges to its full development, and particularly the role played by the current derogation process for use of conventional untreated seed. Also analysed is the lack and inconsistency of information for farmers on what is available and how it meets their needs. In particular, the study compares and identifies gaps in the use of national databases and annual reports on derogations across Europe, and how these can be modified to provide stronger policy incentives to the market. Suppliers were interviewed on technical and economic challenges to seed production and farmers were involved in discussions on how organic seed is acquired and used

Treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia lowers plasma levels of platelet-activating factor and its precursors: a combined metabolomic and lipidomic approach

13openInternationalItalian coauthor/editorIntroduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p < 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value < 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9iopenDi Minno, Alessandro; Orsini, Roberta Clara; Chiesa, Mattia; Cavalca, Viviana; Calcaterra, Ilenia; Tripaldella, Maria; Anesi, Andrea; Fiorelli, Susanna; Eligini, Sonia; Colombo, Gualtiero I; Tremoli, Elena; Porro, Benedetta; Di Minno, Matteo Nicola DarioDi Minno, A.; Orsini, R.C.; Chiesa, M.; Cavalca, V.; Calcaterra, I.; Tripaldella, M.; Anesi, A.; Fiorelli, S.; Eligini, S.; Colombo, G.I.; Tremoli, E.; Porro, B.; Di Minno, M.N.D