Genome Wide Association Studies in Small-Cell Lung Cancer. A Systematic Review.

Small cell lung cancer (SCLC) is one of the deadliest forms of lung cancer, but few information exists regarding the role of genetics, particularly on Genome Wide Association Studies (GWAS). The aim of the study is to explore the evidence available obtained through GWAS studies for SCLC using a systematic review. We performed a literature search in the main databases until July 31st, 2023. We included all human based studies on GWAS for lung cancer which presented results for SCLC. Only studies with participants diagnosed of SCLC with anatomopathological confirmation were included. Fourteen studies were identified; 8 studies showed a relationship between ASCL1 overexpression and SCLC, which may regulate CHRNA5/A3/B4 cluster, producing a consequent nAChR overexpression. Nine papers, including 8 of the previous, found a positive association between SNPs located in chromosome 15 and SCLC. The most important cluster of genes found is CHRNA5/A3/B4 but the mechanism for the role of these genes is unclear. Kyoto Encyclopaedia of Genes and Genome (KEGG) shows that these receptors were found to be overexpressed where nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-Nitrosonornicotine (NNN) acts, involving different routes in SCLC carcinogenesis.

A Genome-Wide Association Study of Small Cell Lung Cancer

Introduction: Small cell lung cancer (SCLC) comprises 10–15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case–control study specifically designed for small cell lung cancer (SCLC). Methods: Incident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure. Results: We included 271 SCLC cases and 557 controls. We found evidence (p-values<10−5) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC. Conclusion: This study provides biological evidence for pathways related to SCLC, offering novel loci for further research. (AU)

A Genome-Wide Association Study of Small Cell Lung Cancer.

INTRODUCTION: Small cell lung cancer (SCLC) comprises 10-15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case-control study specifically designed for small cell lung cancer (SCLC). METHODS: Incident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure. RESULTS: We included 271 SCLC cases and 557 controls. We found evidence (p-values<10-5) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC. CONCLUSION: This study provides biological evidence for pathways related to SCLC, offering novel loci for further research.

Towards the portability of knowledge in reinforcement learning-based systems for automatic drone navigation.

In the field of artificial intelligence (AI) one of the main challenges today is to make the knowledge acquired when performing a certain task in a given scenario applicable to similar yet different tasks to be performed with a certain degree of precision in other environments. This idea of knowledge portability is of great use in Cyber-Physical Systems (CPS) that face important challenges in terms of reliability and autonomy. This article presents a CPS where unmanned vehicles (drones) are equipped with a reinforcement learning system so they may automatically learn to perform various navigation tasks in environments with physical obstacles. The implemented system is capable of isolating the agents' knowledge and transferring it to other agents that do not have prior knowledge of their environment so they may successfully navigate environments with obstacles. A complete study has been performed to ascertain the degree to which the knowledge obtained by an agent in a scenario may be successfully transferred to other agents in order to perform tasks in other scenarios without prior knowledge of the same, obtaining positive results in terms of the success rate and learning time required to complete the task set in each case. In particular, those two indicators showed better results (higher success rate and lower learning time) with our proposal compared to the baseline in 47 out of the 60 tests conducted (78.3%).

Occupation as a risk factor of small cell lung cancer.

Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present.

Social Behavior and COVID-19: Analysis of the Social Factors behind Compliance with Interventions across the United States.

Since its emergence, COVID-19 has caused a great impact in health and social terms. Governments and health authorities have attempted to minimize this impact by enforcing different mandates. Recent studies have addressed the relationship between various socioeconomic variables and compliance level to these interventions. However, little attention has been paid to what constitutes people's response and whether people behave differently when faced with different interventions. Data collected from different sources show very significant regional differences across the United States. In this paper, we attempt to shed light on the fact that a response may be different depending on the health system capacity and each individuals' social status. For that, we analyze the correlation between different societal (i.e., education, income levels, population density, etc.) and healthcare capacity-related variables (i.e., hospital occupancy rates, percentage of essential workers, etc.) in relation to people's level of compliance with three main governmental mandates in the United States: mobility restrictions, mask adoption, and vaccine participation. Our aim was to isolate the most influential variables impacting behavior in response to these policies. We found that there was a significant relationship between individuals' educational levels and political preferences with respect to compliance with each of these mandates.

Scale, context, and heterogeneity: the complexity of the social space.

The social space refers to physical or virtual places where people interact with one another. It decisively influences the emergence of human behaviors. However, little is known about the nature and complexity of the social space, nor its relationship to context and spatial scale. Recently, the science of complex systems has bridged between fields of knowledge to provide quantitative responses to fundamental sociological questions. In this paper, we analyze the shifting behavior of social space in terms of human interactions and wealth distribution across multiple scales using fine-grained data collected from both official (US Census Bureau) and unofficial data sources (social media). We use these data to unveil how patterns strongly depend upon the observation scale. Therefore, it is crucial for any analysis to be framed within the appropriate context to avoid biased results and/or misleading conclusions. Biased data analysis may lead to the adoption of fragile and poor decisions. Including context and a proper understanding of the spatial scale are essential nowadays, especially with the pervasive role of data-driven tools in decision-making processes.

Assessing the risk of pandemic outbreaks across municipalities with mathematical descriptors based on age and mobility restrictions.

By March 14th 2022, Spain is suffering the sixth wave of the COVID-19 pandemic. All the previous waves have been intimately related to the degree of imposed mobility restrictions and its consequent release. Certain factors explain the incidence of the virus across regions revealing the weak locations that probably require some medical reinforcements. The most relevant ones relate with mobility restrictions by age and administrative competence, i.e., spatial constrains. In this work, we aim to find a mathematical descriptor that could identify the critical communities that are more likely to suffer pandemic outbreaks and, at the same time, to estimate the impact of different mobility restrictions. We analyze the incidence of the virus in combination with mobility flows during the so-called second wave (roughly from August 1st to November 30th, 2020) using a SEIR compartmental model. After that, we derive a mathematical descriptor based on linear stability theory that quantifies the potential impact of becoming a hotspot. Once the model is validated, we consider different confinement scenarios and containment protocols aimed to control the virus spreading. The main findings from our simulations suggest that the confinement of the economically non-active individuals may result in a significant reduction of risk, whose effects are equivalent to the confinement of the total population. This study is conducted across the totality of municipalities in Spain.

Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms / El radón, la exposición al tabaco y el riesgo de desarrollar cáncer de pulmón de células no pequeñas en relación con polimorfismos genéticos de BER y NER

Introduction: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers.Methods: A multicentre, hospital-based, case–control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants’ dwellings.Results: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44–5.2) and heavy smokers (OR 3.04; 95%CI 1.21–7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64–58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15–8.48).Conclusion: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent. (AU)

Introducción: El consumo de tabaco y la exposición al radón se consideran la primera y la segunda causa más frecuentes de cáncer de pulmón, respectivamente. El objetivo de este estudio fue analizar si determinados polimorfismos genéticos en los loci que forman parte de la cascada de reparación del ADN se asocian con el cáncer de pulmón de célula no pequeña, y también si es posible que modifiquen la asociación entre la exposición al radón en el hogar y el cáncer de pulmón tanto en fumadores como en no fumadores.Métodos: Se diseñó un estudio multicéntrico hospitalario de casos y controles con 826 casos y 1.201 controles en un área proclive a la presencia de radón. Se determinó el genotipo en sangre y se midió la exposición al radón en el lugar de residencia de los participantes.Resultados: Analizando la exposición al tabaco, la variante del gen NBN (rs1805794) se asoció con el cáncer de pulmón en no fumadores (OR 2,72; IC 95% 1,44-5,2) y grandes fumadores (OR 3,04; IC 95% 1,21-7,69). El polimorfismo con mayor asociación con el cáncer de pulmón fue OGG1 (rs125701), con una OR de 8,04 (IC 95% 1,64-58,29) para la variante genotípica en homocigosis en grandes fumadores. En cuanto a la exposición al radón en interiores (>200Bq/m3), rs1452584 en homocigosis mostró la asociación más fuerte (OR 3,04; IC 95% 1,15-8,48).Conclusión: Los genes que se analizaron no muestran asociación con el modelo completamente ajustado, pero podrían modificar la asociación con el cáncer de pulmón cuando se consideran diferentes categorías de consumo de tabaco (esto es, grandes fumadores). Esta asociación podría aumentar de forma similar en aquellos individuos que están expuestos al radón en interiores, aunque en menor medida. (AU)

Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms.

INTRODUCTION: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. METHODS: A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings. RESULTS: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48). CONCLUSION: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.

Universal electronic consultation (e-consultation) program of a cardiology service. Long-term results.

INTRODUCTION AND OBJECTIVES: Many health systems have initiated electronic consultation (e-consultation) programs, although little is known about their impact on accessibility, safety, and satisfaction. The aim of this study was to assess the clinical impact of the implementation of an outpatient care model that includes an initial e-consultation and to compare it with a one-time face-to-face consultation model. METHODS: We selected patients who visited the cardiology service at least once between 2010 and 2019. Using an interrupted time series regression model, we analyzed the impact of incorporating e-consultation into the health care model (started in 2013), and evaluated waiting times, emergency services, hospital admissions, and mortality. RESULTS: We analyzed 47 377 patients: 61.9% were attended in e-consultation and 38.1% in one-time face-to-face consultations. The waiting time for care was shorter in the e-consultation model (median [IQR]: 7 [5-13] days) than in the face-to-face model (median [IQR]: 33 [14-81] days), P<.001. The interrupted time series regression model showed that the introduction of e-consultation substantially decreased waiting times, which held steady at around 9 days, although with slight oscillations. Patients evaluated via e-consultation had fewer hospital admissions (0.9% vs 1.2%, P=.0017) and lower mortality (2.5% vs 3.9%, P<.001). CONCLUSIONS: An outpatient care program that includes an e-consultation reduced waiting times significantly and was safe, with a lower rate of hospital admissions and mortality in the first year.

Risk evaluation at municipality level of a COVID-19 outbreak incorporating relevant geographic data: the study case of Galicia.

The COVID-19 pandemic was an inevitable outcome of a globalized world in which a highly infective disease is able to reach every country in a matter of weeks. While lockdowns and strong mobility restrictions have proven to be efficient to contain the exponential transmission of the virus, its pervasiveness has made it impossible for economies to maintain this kind of measures in time. Understanding precisely how the spread of the virus occurs from a territorial perspective is crucial not only to prevent further infections but also to help with policy design regarding human mobility. From the large spatial differences in the behavior of the virus spread we can unveil which areas have been more vulnerable to it and why, and with this information try to assess the risk that each community has to suffer a future outbreak of infection. In this work we have analyzed the geographical distribution of the cumulative incidence during the first wave of the pandemic in the region of Galicia (north western part of Spain), and developed a mathematical approach that assigns a risk factor for each of the different municipalities that compose the region. This risk factor is independent of the actual evolution of the pandemic and incorporates geographic and demographic information. The comparison with empirical information from the first pandemic wave demonstrates the validity of the method. Our results can potentially be used to design appropriate preventive policies that help to contain the virus.

Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma.

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens. Multiple microscopic clear cell clusters were present in the cortex, often in subcapsular location. They were composed of large epithelial cells with strikingly clear cytoplasm, without nuclear atypia, arranged in solid nests, and some tubules with narrow lumina. Immunohistochemically, they were positive for AE1AE3, PAX 8, EMA, kidney-specific cadherin, cytokeratin 7, E cadherin, and CD117, with focal immunoreactivity for CD10. Carbonic anhydrase IX, vimentin, and markers related to apoptosis and proliferation were negative. Ultrastructurally, the cytoplasms were enlarged and poor in organelles, showing ballooning degeneration. Array comparative genomic hybridization showed no chromosomal gains or losses. Clear cell clusters constitute a rare finding in the kidney and must be differentiated from benign lesions (ectopic adrenal tissue, osmotic tubulopathy, histiocytic clusters, renal adenomas) and renal cell carcinomas. Clear cell clusters appear to be generated from "endocrine-type" atrophic tubules whose cells are enlarged due to intracellular oedema. Immunohistochemistry shows a distal nephron phenotype with a limited expression of a proximal marker, CD10. Coexisting chronic renal disease or ischemic conditions seem to be related to the development of clear cell clusters. Pathological, ultrastructural, and cytogenomic features do not support a preneoplastic nature of this lesion, at least in the cases studied here.

Supresión de angiotensia II en la infección por el virus SARS-CoV-2: una propuesta terapeútica / Angiotensin II suppression in SARS-CoV-2 infection: a therapeutic approach

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The botanist George Gardner and his impressions of slave culture in Brazil: Rio de Janeiro, 1810-1850. / O botânico George Gardner e suas impressões sobre a cultura escrava no Brasil: Rio de Janeiro, 1810-1850.

This article analyzes the English botanist George Gardner's trip to Brazil during the 1830s. After graduating from the University of Glasgow Gardner was influenced by his teacher and by readings of contemporary naturalists and set off for Brazil in March of 1836, arriving two months later in Rio de Janeiro. The article presents Gardner's impressions of slavery in Brazil, in an attempt to unveil the symbolic universe of a play he witnessed and described, which took place on a farm in Rio de Janeiro on Christmas night. By describing black slavery in its routes across the Atlantic, we compare this event with other similar happenings in Brazil and in Trinidad and Tobago.

Resumo Analisa a viagem do britânico George Gardner ao Brasil durante os anos 1830. Após se graduar em história natural pela Universidade de Glasgow, influenciado por seu professor e por leituras de naturalistas de seu tempo, Gardner embarcou para o Brasil em março de 1836, chegando ao Rio de Janeiro dois meses depois. O artigo apresenta suas impressões sobre a escravidão no Brasil, procurando desvendar o universo simbólico de uma representação dramática descrita por ele, ocorrida em uma fazenda do Rio de Janeiro no dia de Natal. Desvelando a escravidão negra em seus circuitos atlânticos, comparamos o evento com outros semelhantes ocorridos no Brasil e em Trinidad e Tobago.

O botânico George Gardner e suas impressões sobre a cultura escrava no Brasil: Rio de Janeiro, 1810-1850 / The botanist George Gardner and his impressions of slave culture in Brazil: Rio de Janeiro, 1810-1850

Resumo Analisa a viagem do britânico George Gardner ao Brasil durante os anos 1830. Após se graduar em história natural pela Universidade de Glasgow, influenciado por seu professor e por leituras de naturalistas de seu tempo, Gardner embarcou para o Brasil em março de 1836, chegando ao Rio de Janeiro dois meses depois. O artigo apresenta suas impressões sobre a escravidão no Brasil, procurando desvendar o universo simbólico de uma representação dramática descrita por ele, ocorrida em uma fazenda do Rio de Janeiro no dia de Natal. Desvelando a escravidão negra em seus circuitos atlânticos, comparamos o evento com outros semelhantes ocorridos no Brasil e em Trinidad e Tobago.

Abstract This article analyzes the English botanist George Gardner's trip to Brazil during the 1830s. After graduating from the University of Glasgow Gardner was influenced by his teacher and by readings of contemporary naturalists and set off for Brazil in March of 1836, arriving two months later in Rio de Janeiro. The article presents Gardner's impressions of slavery in Brazil, in an attempt to unveil the symbolic universe of a play he witnessed and described, which took place on a farm in Rio de Janeiro on Christmas night. By describing black slavery in its routes across the Atlantic, we compare this event with other similar happenings in Brazil and in Trinidad and Tobago.

A Reinforcement Learning Model Equipped with Sensors for Generating Perception Patterns: Implementation of a Simulated Air Navigation System Using ADS-B (Automatic Dependent Surveillance-Broadcast) Technology.

Over the last few decades, a number of reinforcement learning techniques have emerged, and different reinforcement learning-based applications have proliferated. However, such techniques tend to specialize in a particular field. This is an obstacle to their generalization and extrapolation to other areas. Besides, neither the reward-punishment (r-p) learning process nor the convergence of results is fast and efficient enough. To address these obstacles, this research proposes a general reinforcement learning model. This model is independent of input and output types and based on general bioinspired principles that help to speed up the learning process. The model is composed of a perception module based on sensors whose specific perceptions are mapped as perception patterns. In this manner, similar perceptions (even if perceived at different positions in the environment) are accounted for by the same perception pattern. Additionally, the model includes a procedure that statistically associates perception-action pattern pairs depending on the positive or negative results output by executing the respective action in response to a particular perception during the learning process. To do this, the model is fitted with a mechanism that reacts positively or negatively to particular sensory stimuli in order to rate results. The model is supplemented by an action module that can be configured depending on the maneuverability of each specific agent. The model has been applied in the air navigation domain, a field with strong safety restrictions, which led us to implement a simulated system equipped with the proposed model. Accordingly, the perception sensors were based on Automatic Dependent Surveillance-Broadcast (ADS-B) technology, which is described in this paper. The results were quite satisfactory, and it outperformed traditional methods existing in the literature with respect to learning reliability and efficiency.

La Creencia en un Mundo Justo como Trasfondo Ideológico de la Representación Social de la Justicia / Belief in a Just World as Ideological Background for the Social Representation of Justice / A Crença num Mundo Justo como Fundo Ideológico da Representação Social da Justiça

El objetivo de este trabajo es analizar las relaciones entre representaciones sociales e ideología, mediante el estudio de las relaciones entre la creencia ideológica en un mundo justo (CMJ) y la representación social de la justicia. Se administró la técnica de asociación de palabras y la escala Global de CMJ a 404 estudiantes universitarios argentinos. El núcleo central de la representación social expresa un sentido retributivo, aunque se identificaron diferencias en sus elementos periféricos. Los individuos con CMJ baja y media consideran la justicia como una institución social con errores en su funcionamiento, mientras que los individuos con alta CMJ la piensan por fuera de la sociedad, sin calificarla.

The objective of this paper is to analyze the relationships between social representations and ideology through the study of the relationship between ideological belief in a just world (BJW) and the social representation of justice. The technique of word association was used, and the BJW general scale was administered to 404 Argentinian university students. The core of the social representation expresses a retributive meaning, although differences in peripheral elements were identified. Individuals with low and medium BJW consider justice to be a social institution with errors in its operation, whereas individuals with high BJW think of justice as something beyond society, without qualifying it.

O objetivo deste trabalho é analisar as relações entre representações sociais e ideologia, mediante o estudo das relações entre a crença ideológica num mundo justo (CMJ) e a representação social da justiça. Administrou-se a técnica de associação de palavras e da escala Global de CMJ a 404 estudantes universitários argentinos. O núcleo central da representação social expressa um sentido compensativo, embora tenham sido identificadas diferenças em seus elementos periféricos. Os indivíduos com CMJ baixa e média consideram a justiça como uma instituição social com erros em seu funcionamento, enquanto os indivíduos com alta CMJ pensam-na por fora da sociedade, sem qualificá-la.