Pervasive conditional selection of driver mutations and modular epistasis networks in cancer

Cancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistatic interactions and their quantitative effect on tumor evolution remains a challenge. We developed a method to quantify COnditional SELection on the Excess of Nonsynonymous Substitutions (Coselens) in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identified 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection accounts for 25-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario, where gene-specific across-pathway interactions shape differentiated cancer subtypes.

Information and Communication Technologies in the Educational Process

The study aimed to map the critical success factors for the adoption of information and communication technologies (ICTs) in the educational process of educational institutions. Problems related to the adoption of ICT in the educational system stem from the need to adapt to the use of new technologies in the internal processes of institutions and in teaching and learning processes, common to different profiles of educational institutions including of engineering courses with them specificities. To meet the objective, a review of the existing bibliography in the Scopus database was carried out to highlight articles relevant to the topic. Based on the review, 31 articles identified the main factors and effects that influence and impact the process of implementation and continued use of ICTs. The survey generated a broader view of the challenges faced in different dimensions, from SWOT framework, involving different stakeholders. It is suggested in future studies to engineering analyze deeper the complex scenario that involves the theme.

Modeling a Cyber Defense Business Ecosystem of Ecosystems

Providing cyber defense in a country is complex. It involves ensuring the security of various products and services that are part of a global supply chain. In this complex scenario, the challenge is the development of a cyber defense business ecosystem that, reaching a minimum level of maturity, guarantees the security of products and services in cyberspace. This work proposes a cyber defense business ecosystem of ecosystems (BEoE) model with two ecosystems that must be created or fostered, the human resources training ecosystem and the product and service homologation and certification ecosystem. These two cyber defense ecosystems are key to the sustainable growth of an entire chain of production and sourcing of cyber defense goods and services. The proposed model allows the Cyber Defense BEoE to evolve, so that different actors (companies and government agencies) with different levels of maturity in defense and cybersecurity may emerge. In this way, a country's Cyber Defense BEoE may be able to provide products and services at different levels of security for its defense system.

First Attempt to Couple Proteomics with the AhR Reporter Gene Bioassay in Soil Pollution Monitoring and Assessment

A topsoil sample obtained from a highly industrialized area (Taranto, Italy) was tested on the DR-CALUX® cell line and the exposed cells processed with proteomic and bioinformatics analyses. The presence of polyhalogenated compounds in the topsoil extracts was confirmed by GC-MS/MS analysis. Proteomic analysis of the cells exposed to the topsoil extracts identified 43 differential proteins. Enrichment analysis highlighted biological processes, such as the cellular response to a chemical stimulus, stress, and inorganic substances; regulation of translation; regulation of apoptotic process; and the response to organonitrogen compounds in light of particular drugs and compounds, extrapolated by bioinformatics all linked to the identified protein modifications. Our results confirm and reflect the complex epidemiological situation occurring among Taranto inhabitants and underline the need to further investigate the presence and sources of inferred chemicals in soils. The combination of bioassays and proteomics reveals a more complex scenario of chemicals able to affect cellular pathways and leading to toxicities rather than those identified by only bioassays and related chemical analysis. This combined approach turns out to be a promising tool for soil risk assessment and deserves further investigation and developments for soil monitoring and risk assessment.

Costs of treating community-acquired bacterial bronchopneumonia in pediatric patients

Relevance. Health management has not escaped the pressure of the current epidemiological situation. In a complex scenario, characterized by the COVID-19 pandemic, the daily dynamics become more complex and greater agility is required for decision-making. Much of the success of those decisions is determined by access to timely information, especially in crisis conditions and limited resources. For this reason, health organizations are interested in knowing the costs of pathologies that frequently constitute causes of hospitalization. In this sense, community - acquired bacterial bronchopneumonia stands out, which is a disease that frequently causes hospitalization of pediatric patients. Objective. This article aims to carry out a partial retrospective financial evaluation in order to determine the costs associated with the treatment of community-acquired bacterial bronchopneumonia in pediatric patients. Materials and methods. The study was developed from the perspective of the health institution General Hospital Guillermo Luis Fernndez Hernndez - Baquero in the city of Moa. For this, the analysis - synthesis and comparative methods were used, as well as the methodology to calculate and analyze disease costs. Results. The research focused on the January-March quarters of the years 2017 and 2018 and provided valuable accounting information regarding the direct and indirect costs of the treatment of the pathology in question, which serves as a tool for the correct management of the hospital institution. Conclusion . The direct costs exceeded the indirect costs and the items that most affected the total cost were the salaries of the workers, food, and medicines used to treat the disease. The need to develop digital health was evidenced, with special emphasis on digital medical records to facilitate access to them and thus avoid the loss of information due to its deterioration. The study provides useful information to the management of the health institution, which serves as support for budget analysis and future projections.

AdmixSim 2: a forward-time simulator for modeling complex population admixture

Background Computer simulations have been widely applied in population genetics and evolutionary studies. A great deal of effort has been made over the past two decades in developing simulation tools. However, there are not many simulation tools suitable for studying population admixture. Results We here developed a forward-time simulator, AdmixSim 2, an individual-based tool that can flexibly and efficiently simulate population genomics data under complex evolutionary scenarios. Unlike its previous version, AdmixSim 2 is based on the extended Wright-Fisher model, and it implements many common evolutionary parameters to involve gene flow, natural selection, recombination, and mutation, which allow users to freely design and simulate any complex scenario involving population admixture. AdmixSim 2 can be used to simulate data of dioecious or monoecious populations, autosomes, or sex chromosomes. To our best knowledge, there are no similar tools available for the purpose of simulation of complex population admixture. Using empirical or previously simulated genomic data as input, AdmixSim 2 provides phased haplotype data for the convenience of further admixture-related analyses such as local ancestry inference, association studies, and other applications. We here evaluate the performance of AdmixSim 2 based on simulated data and validated functions via comparative analysis of simulated data and empirical data of African American, Mexican, and Uyghur populations. Conclusions AdmixSim 2 is a flexible simulation tool expected to facilitate the study of complex population admixture in various situations.

Ghana

This chapter investigates the politics of parliamentary debates in Ghana, a country that combines a hybrid presidential regime with a candidate-centered electoral system. Although these features place Ghana as a typical case in which parliamentary rules grant more leeway to individual MPs, our analysis reveals a more complex scenario that defies conventional wisdom. The partial linkage between the legislative and parliamentary branches gives the executive strong agenda-setting powers; moreover, party leadership’s marked influence in the way business in the House unfolds means that there is a skewed playing field, which curtails individual MPs’ access to the floor. The empirical section draws on an original dataset of legislative debates from 2005 through 2019 to examine the determinants of floor access in the Ghanaian parliament. Three findings merit highlighting. First, female MPs are less likely to be selected to speak, and their speeches are significantly shorter when compared to those of male MPs. Second, seniority and exposure to parliament increase the chances of participating in a debate. Third, party leaders have most access to the floor, followed by committee chairs and ministers. However, female MPs who are members of the party leadership speak significantly less than their male counterparts.

Nudo territorial y desterritorialización indígena en Loma Campana (Neuquén, Argentina) desde 1963.

El escrito analiza cómo las políticas estatales provinciales configuraron nudos territoriales en la zona donde se ubica la comunidad Campo Maripe, al norte de Añelo, el corazón de la formación geológica Vaca Muerta. Se sostiene que estas políticas diseñaron los espacios impulsando territorialidades asociadas a determinadas actividades económicas y trajeron como consecuencia la desterritorialización indígena. La comunidad Campo Maripe, cuyo territorio actualmente se superpone parcialmente con el yacimiento hidrocarburífero Loma Campana -uno de los tres más relevantes en la extracción por métodos no convencionales-, ha sido seleccionada como caso de estudio en función de la notoriedad de sus estrategias de resistencia durante los últimos años. Se utilizan fuentes escritas y orales para caracterizar el complejo panorama de la superposición de territorialidades a partir de las políticas provinciales y el desarrollo de dinámicas específicas en las interacciones de los diferentes actores dentro de los nudos territoriales. The paper analyses how Neuquen’s state policies configured territorial knots in the area where the mapuce community Campo Maripe is located, in northern Añelo, the core of the Vaca Muerta geological formation. It is argued that these policies designed spaces boosting certain economic activities and their associated territorialities and brought indigenous deterritorialization as a consequence. The Mapuce community Campo Maripe, whose territory currently partially overlaps with the Loma Campana oil field -one of the three most important fields in the extraction of hydrocarbons by non-conventional methods-, has been selected as a case study due to how notorious its resistance strategies have become over the last few years. Written documents and oral testimonies are used to characterize the complex scenario of territorial overlapping caused by state policies and the development of specific interactions between the different actors within the territorial knots.

The Common Combination of Aortic Stenosis with Mitral Regurgitation: Diagnostic Insight and Therapeutic Implications in the Modern Era of Advanced Echocardiography and Percutaneous Intervention

The combination of aortic stenosis (AS) and mitral regurgitation (MR) is common in patients with degenerative valvular disease. It is characterized by having complex pathophysiology, leading to potential diagnostic pitfalls. Evidence is scarce in the literature to direct the diagnostic framework and treatment of patients with this particular combination of multiple valvular diseases. In this complex scenario, the appropriate use of advanced echocardiography and multimodality imaging methods plays a central role. Transcatheter mitral valve replacement or repair and transcatheter aortic valve replacement widen the surgical options for valve diseases. Therefore, there is an increasing need to reconsider the function, timing, and mode intervention for patients with a combination of AS with MR towards more personalized treatment.