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Bartolina Xixa desarma el relato de una argentinidad blanca, heteronormada y homogénea, a través de su arte transformista. Al bailar una vidala usando como escenario un basural a cielo abierto, cuestiona la cultura afectiva del folklore y presenta una estructura de sentimientos elaborada sobre la experiencia de la exclusión permanente. Bartolina lleva a la coreografía el movimiento que la desplaza entre diferentes identificaciones: se muestra como “vestida”, indígena, de género fluido, fronteriza y precaria. La vidala titulada “Ramita seca”, mediante la fusión de sonoridades provenientes de la vidala y el rap, ofrece formas de retención que permiten elaborar una narración colectiva del dolor incorporando lo abyecto, lo excluido y lo antagónico a la narrativa del folklore. “Ramita seca” interpretada por Bartolina, propone la emergencia de un folklore de resistencia que habilita otros repertorios sociales y estilos emocionales bajo los cuales devenir sujeto.

In this Perspective we review some recent advances in the concept of atoms-in-molecules from a real space perspective.

The absolute entropy of a flexible molecule can be approximated by the sum of a rigid-rotor-harmonic-oscillator (RRHO) entropy and a Gibbs-Shannon entropy associated to the Boltzmann distribution for the occupation of the conformational energy levels. Herein, we show that such partitioning, which has received renewed interest, leads to accurate entropies of single molecules of increasing size provided that the conformational part is estimated by means of a set of discretization and expansion techniques that are able to capture the significant correlation effects among the torsional motions. To ensure a reliable entropy estimation, we rely on extensive sampling as that produced by classical molecular dynamics simulations on the microsecond time scale, which is currently affordable for small- and medium-sized molecules. According to test calculations, the gas-phase entropy of simple organic molecules is predicted with a mean unsigned error of 0.9 cal/(mol K) when the RRHO entropies are computed at the B3LYP-D3/cc-pVTZ level. Remarkably, the same protocol gives small errors [1 cal/(mol K)] for the extremely flexible linear alkane molecules (C

During the learning process, a child develops a mental representation of the task he or she is learning. A Machine Learning algorithm develops also a latent representation of the task it learns. We investigate the development of the knowledge construction of an artificial agent through the analysis of its behavior, i.e., its sequences of moves while learning to perform the Tower of Hanoï (TOH) task. The TOH is a well-known task in experimental contexts to study the problem-solving processes and one of the fundamental processes of children’s knowledge construction about their world. We position ourselves in the field of explainable reinforcement learning for developmental robotics, at the crossroads of cognitive modeling and explainable AI. Our main contribution proposes a 3-step methodology named Implicit Knowledge Extraction with eXplainable Artificial Intelligence (IKE-XAI) to extract the implicit knowledge, in form of an automaton, encoded by an artificial agent during its learning. We showcase this technique to solve and explain the TOH task when researchers have only access to moves that represent observational behavior as in human–machine interaction. Therefore, to extract the agent acquired knowledge at different stages of its training, our approach combines: first, a Q-learning agent that learns to perform the TOH task; second, a trained recurrent neural network that encodes an implicit representation of the TOH task; and third, an XAI process using a post-hoc implicit rule extraction algorithm to extract finite state automata. We propose using graph representations as visual and explicit explanations of the behavior of the Q-learning agent. Our experiments show that the IKEXAI approach helps understanding the development of the Q-learning agent behavior by providing a global explanation of its knowledge evolution during learning. IKE-XAI also allows researchers to identify the agent’s Aha! moment by determining from what moment the knowledge representation stabilizes and the agent no longer learns., Region Bretagne, European Union via the FEDER program, Spanish Government Juan de la Cierva Incorporacion - MCIN/AEI IJC2019-039152-I, Google Research Scholar Grant

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important regulator of extracellular matrix turnover that has been traditionally regarded as a potential tumor suppressor owing to its inhibitory effects of matrix metalloproteinases. Intriguingly, this interpretation has been challenged by the consistent observation that increased expression of TIMP-1 is associated with poor prognosis in virtually all cancer types including lung cancer, supporting a tumor-promoting function. However, how TIMP-1 is dysregulated within the tumor microenvironment and how it drives tumor progression in lung cancer is poorly understood. We analyzed the expression of TIMP-1 and its cell surface receptor CD63 in two major lung cancer subtypes: lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), and defined the tumor-promoting effects of their interaction. We found that TIMP-1 is aberrantly overexpressed in tumor-associated fibroblasts (TAFs) in ADC compared to SCC. Mechanistically, TIMP-1 overexpression was mediated by the selective hyperactivity of the pro-fibrotic TGF-β1/SMAD3 pathway in ADC-TAFs. Likewise, CD63 was upregulated in ADC compared to SCC cells. Genetic analyses revealed that TIMP-1 secreted by TGF-β1-activated ADC-TAFs is both necessary and sufficient to enhance growth and invasion of ADC cancer cells in culture, and that tumor cell expression of CD63 was required for these effects. Consistently, in vivo analyses revealed that ADC cells co-injected with fibroblasts with reduced SMAD3 or TIMP-1 expression into immunocompromised mice attenuated tumor aggressiveness compared to tumors bearing parental fibroblasts. We also found that high TIMP1 and CD63 mRNA levels combined define a stronger prognostic biomarker than TIMP1 alone. Our results identify an excessive stromal TIMP-1 within the tumor microenvironment selectively in lung ADC, and implicate it in a novel tumor-promoting TAF-carcinoma crosstalk, thereby pointing to TIMP-1/CD63 interaction as a novel therapeutic target in lung cancer.

The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the self-assembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases., This work was supported by the projects PID2020-115663GB-C3-2, PID2019-108794GB-I00, and PID2020–115631GB-I00 funded by MCIN/AEI/10.13039/501100011033 from the Ministerio de Ciencia e Innovación. We thank AGAUR for a grant to consolidated research groups 2017SGR1277. A.G.-C. and N.A.-A. acknowledge the financial support from the Spanish Ministry Science, through the “Severo Ochoa” Programme for Centres of Excellence (FUNFUTURE) (2020-2023). A.G.-C. also acknowledges a Ramon y Cajal Grant (RYC-2017-22910)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Resumen Este artículo ahonda en el vínculo del discurso con la salud. El objetivo del estudio es examinar las vivencias de violencia institucional que han padecido las pacientes con endometriosis mediante el análisis de la argumentación. El marco metodológico es eminentemente cualitativo. El corpus consta de treinta entrevistas semiestructuradas a mujeres chilenas con endometriosis diagnosticada. Se analizan los esquemas argumentativos (Toulmin, 1958/2007; Pardo, 2011 y Molina, 2012) presentes en los relatos autobiográficos de estas mujeres cuando abordan un episodio de violencia institucional padecido. Los resultados del análisis demuestran que tanto los datos como las conclusiones se basan en hechos vivenciados por ellas en sus interacciones con los médicos o el sistema de atención público de salud, quienes representan a los actores sociales más frecuentes en estos relatos. Además, las garantías expuestas dan cuenta de creencias sociales que obstaculizan la relación médico-paciente. Esto permite concluir cómo los episodios de violencia son reiterados en el quehacer clínico, lo que expone aún más a estas pacientes a nuevas dolencias. Abstract This article delves into the link between discourse and health. The objective of study is examining the experiences of institutional violence that patients with endometriosis have suffered through the analysis of the argumentation. The methodological framework is eminently qualitative. The corpus consists of thirty semi-structured interviews with Chilean women with diagnosed endometriosis. The argumentative schemes (Toulmin, 1958; Pardo, 2011 and Molina, 2012) present in the autobiographical accounts of these women when they deal with an episode of institutional violence suffered are analyzed. The results show that both the data and the conclusions are based on facts experienced by the patients in their interactions with their doctors or the public health care system, who represent the most frequent social actors in these stories. In addition, the guarantees exposed show social beliefs that hinder the doctor-patient relationship. This allows us to conclude how episodes of violence are repeated in clinical practice, which further exposes these patients to new ailments. Resumo Este artigo investiga a articulação entre discurso e saúde. O objetivo deste estudo é examinar experiências de violência institucional que as pacientes com endometriose sofreram através da análise da argumentação. O quadro metodológico é eminentemente qualitativo. O corpus consiste em trinta entrevistas semiestruturadas com mulheres chilenas com diagnóstico de endometriose. São analisados os esquemas argumentativos (Toulmin, 1958; Pardo, 2011 e Molina, 2012) presentes nos relatos autobiográficos dessas mulheres ao lidarem com um episódio de violência institucional sofrido. Os resultados da análise mostram que tanto os dados quanto as conclusões são baseados em fatos vivenciados por eles em suas interações com seus médicos ou o sistema público de saúde, que representam os atores sociais mais frequentes nessas histórias. Além disso, as garantias expostas evidenciam crenças sociais que dificultam a relação médico-paciente. Isso permite concluir como os episódios de violência são repetidos na prática clínica, o que expõe ainda mais esses pacientes a novos males.

Mechanical changes in tumors have long been linked to increased malignancy and therapy resistance and attributed to mechanical changes in the tumor extracellular matrix (ECM). However, to the best of our knowledge, there have been no mechanical studies on decellularized tumors. Here, we studied the biochemical and mechanical progression of the tumor ECM in two models of lung metastases: lung carcinoma (CAR) and melanoma (MEL). We decellularized the metastatic lung sections, measured the micromechanics of the tumor ECM, and stained the sections for ECM proteins, proliferation, and cell death markers. The same methodology was applied to MEL mice treated with the clinically approved anti-fibrotic drug nintedanib. When compared to healthy ECM (~0.40 kPa), CAR and MEL lung macrometastases produced a highly dense and stiff ECM (1.79 ± 1.32 kPa, CAR and 6.39 ± 3.37 kPa, MEL). Fibronectin was overexpressed from the early stages (~118%) to developed macrometastases (~260%) in both models. Surprisingly, nintedanib caused a 4-fold increase in ECM-occupied tumor area (5.1 ± 1.6% to 18.6 ± 8.9%) and a 2-fold in-crease in ECM stiffness (6.39 ± 3.37 kPa to 12.35 ± 5.74 kPa). This increase in stiffness strongly correlated with an increase in necrosis, which reveals a potential link between tumor hypoxia and ECM deposition and stiffness. Our findings highlight fibronectin and tumor ECM mechanics as attractive targets in cancer therapy and support the need to identify new anti-fibrotic drugs to abrogate aberrant ECM mechanics in metastases.

Andreas Holzinger acknowledges funding support from the Austrian Science Fund (FWF), Project: P-32554 explainable Artificial Intelligence and from the European Union's Horizon 2020 research and innovation program under grant agreement 826078 (Feature Cloud). This publication reflects only the authors' view and the European Commission is not responsible for any use that may be made of the information it contains; Natalia Diaz-Rodriguez is supported by the Spanish Government Juan de la Cierva Incorporacion contract (IJC2019-039152-I); Isabelle Augenstein's research is partially funded by a DFF Sapere Aude research leader grant; Javier Del Ser acknowledges funding support from the Basque Government through the ELKARTEK program (3KIA project, KK-2020/00049) and the consolidated research group MATHMODE (ref. T1294-19); Wojciech Samek acknowledges funding support from the European Union's Horizon 2020 research and innovation program under grant agreement No. 965221 (iToBoS), and the German Federal Ministry of Education and Research (ref. 01IS18025 A, ref. 01IS18037I and ref. 0310L0207C); Igor Jurisica acknowledges funding support from Ontario Research Fund (RDI 34876), Natural Sciences Research Council (NSERC 203475), CIHR Research Grant (93579), Canada Foundation for Innovation (CFI 29272, 225404, 33536), IBM, Ian Lawson van Toch Fund, the Schroeder Arthritis Institute via the Toronto General and Western Hospital Foundation., Medical artificial intelligence (AI) systems have been remarkably successful, even outperforming human performance at certain tasks. There is no doubt that AI is important to improve human health in many ways and will disrupt various medical workflows in the future. Using AI to solve problems in medicine beyond the lab, in routine environments, we need to do more than to just improve the performance of existing AI methods. Robust AI solutions must be able to cope with imprecision, missing and incorrect information, and explain both the result and the process of how it was obtained to a medical expert. Using conceptual knowledge as a guiding model of reality can help to develop more robust, explainable, and less biased machine learning models that can ideally learn from less data. Achieving these goals will require an orchestrated effort that combines three complementary Frontier Research Areas: (1) Complex Networks and their Inference, (2) Graph causal models and counterfactuals, and (3) Verification and Explainability methods. The goal of this paper is to describe these three areas from a unified view and to motivate how information fusion in a comprehensive and integrative manner can not only help bring these three areas together, but also have a transformative role by bridging the gap between research and practical applications in the context of future trustworthy medical AI. This makes it imperative to include ethical and legal aspects as a cross-cutting discipline, because all future solutions must not only be ethically responsible, but also legally compliant., Austrian Science Fund (FWF) P-32554, European Union's Horizon 2020 research and innovation program 826078 965221, Spanish Government Juan de la Cierva Incorporacion IJC2019-039152-I, DFF Sapere Aude research leader grant, Basque Government KK-2020/00049, consolidated research group MATHMODE T1294-19, Federal Ministry of Education & Research (BMBF) 01IS18025 A 01IS18037I 0310L0207C, Ontario Research Fund RDI 34876, Natural Sciences Research Council NSERC 203475, Canadian Institutes of Health Research (CIHR) 93579, Canada Foundation for Innovation CGIAR CFI 29272 225404 33536, International Business Machines (IBM), Ian Lawson van Toch Fund, Schroeder Arthritis Institute via the Toronto General and Western Hospital Foundation

Actualmente el mercado laboral se encuentra saturado en el sentido de que, dentro de los campos, la mayoría de los profesionales cumplen con el mismo perfil; de esto, el interés y la importancia de que cada uno de los estudiantes universitarios, que están a punto de verse envueltos en un ambiente laboral, consideren la creación de su propia marca personal para que estos puedan ser diferenciados de la homogeneidad y sus atributos sean destacados, permitiéndoles alcanzar su camino de éxito.

A quantitative assessment of the global importance of an agent in a team is as valuable as gold for strategists, decision-makers, and sports coaches. Yet, retrieving this information is not trivial since in a cooperative task it is hard to isolate the performance of an individual from the one of the whole team. Moreover, it is not always clear the relationship between the role of an agent and his personal attributes. In this work we conceive an application of the Shapley analysis for studying the contribution of both agent policies and attributes, putting them on equal footing. Since the computational complexity is NP-hard and scales exponentially with the number of participants in a transferable utility coalitional game, we resort to exploiting a-priori knowledge about the rules of the game to constrain the relations between the participants over a graph. We hence propose a method to determine a Hierarchical Knowledge Graph of agents' policies and features in a Multi-Agent System. Assuming a simulator of the system is available, the graph structure allows to exploit dynamic programming to assess the importances in a much faster way. We test the proposed approach in a proof-of-case environment deploying both hardcoded policies and policies obtained via Deep Reinforcement Learning. The proposed paradigm is less computationally demanding than trivially computing the Shapley values and provides great insight not only into the importance of an agent in a team but also into the attributes needed to deploy the policy at its best., Accepted for publication in Elsevier's Knowledge-Based Systems

Background Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed. Results Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around − 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage. Conclusion TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment. Graphical Abstract

We introduce an approach called PLENARY (exPlaining bLack-box modEls in Natural lAnguage thRough fuzzY linguistic summaries), which is an explainable classifier based on a data-driven predictive model. Neural learning is exploited to derive a predictive model based on two levels of labels associated with the data. Then, model explanations are derived through the popular SHapley Additive exPlanations (SHAP) tool and conveyed in a linguistic form via fuzzy linguistic summaries. The linguistic summarization allows translating the explanations of the model outputs provided by SHAP into statements expressed in natural language. PLENARY accounts for the imprecision related to model outputs by summarizing them into simple linguistic statements and for the imprecision related to the data labeling process by including additional domain knowledge in the form of middle-layer labels. PLENARY is validated on preprocessed speech signals collected from smartphones from patients with bipolar disorder and on publicly available mental health survey data. The experiments confirm that fuzzy linguistic summarization is an effective technique to support meta-analyses of the outputs of AI models. Also, PLENARY improves explainability by aggregating low-level attributes into high-level information granules, and by incorporating vague domain knowledge into a multi-task sequential and compositional multilayer perceptron. SHAP explanations translated into fuzzy linguistic summaries significantly improve understanding of the predictive modelling process and its outputs., Small Grants Scheme within the research project "Bipolar disorder prediction with sensor-based semi-supervised Learning (BIPOLAR)" NOR/SGS/BIPO LAR/0239/2020-00, European Commission RPMA.01.02.00-14-5706/16-00, Systems Research Institute Polish Academy of Sciences, Juan de la Cierva Incorporacion grant - MCIN/AEI IJC2019-039152-I, Google Research Scholar Program, Italian Ministry of University and Research through the European PON project AIM (Attraction and International Mobility) 1852414

Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promotes the Warburg effect and ROS production, which inhibits PTP1B to augment CAV1 phosphorylation on tyrosine-14, thereby increasing the metastatic potential of cancer cells.

Debido a los avances en las neurociencias, la evolución y accesibilidad a dispositivos biométricos, que permiten la captura de respuestas fisiológicas ante estímulos externos, se ha presentado una forma diferente de conocer al consumidor y poder adaptar todas las estrategias de mercadeo lo más personalizado posible en una disciplina llamada Neuromarketing. Atendiendo a esta realidad, el objetivo de la presente investigación es analizar de forma experimental la percepción frente a ciertos estímulos sensoriales derivados de cinco sabores (vainilla, fresa, chocolate, chicle y cookies and cream) de malteadas pertenecientes a la industria de helados y postres. Se realizó una muestra de 20 sujetos, seleccionados mediante una entrevista semiestructurada para garantizar que no habían consumido los sabores de esas malteadas. Posteriormente, fueron expuestos a los cinco sabores en tres momentos diferentes, sólo con el olfato como primer momento, sólo con el canal sensorial del gusto y, por último, sólo con el canal sensorial de la vista. Esto nos permitió capturar la actividad cerebral de ondas (theta, alpha, beta y hi-beta), y también la actividad galvánica, mediante un electroencefalograma (EEG) y un medidor (GSR). Los resultados permitieron observar que los sabores de chocolate y fresa son los que mostraron más cambios y diferencias de género, así mismo, el canal del olfato es el que mayor incidencia tiene en la forma como se perciben los sabores Due to the advances in neuroscience, the evolution and the accessibility of biometric devices, it is possible to capture physiological responses caused by external stimulus, thanks to this a different way to know the consumer has been presented in order to adapt marketing strategies and to make them as personalized as possible in a discipline called Neuromarketing. Realizing this, the aim of this research is to experimentally analyze the perception of certain sensory stimulus derived from five shake flavors (vanilla, strawberry, chocolate, gum and cookies and cream), flavors that we commonly find in the dessert and ice cream industry. We applied a semi-structured interview to find out some people who have never tasted those shake flavors, the final sample was made of 20 people. Subsequently, the 20 people were exposed to the five flavors at three different times. only with smell as the first moment, only with the sensory channel of taste and, finally, only with the sensory channel of sight. This made possible to capture brain wave activity (theta, alpha, beta and hi-beta), as well as galvanic activity, using an electroencephalogram (EEG) and a meter (GSR). The results showed that the chocolate and strawberry flavors evidenced the most changes and gender differences, likewise, the smell channel is the one that has the greatest impact on the way flavors are perceived

The COVID-19 pandemic has spurred a large amount of experimental and observational studies reporting clear correlation between the risk of developing severe COVID-19 (or dying from it) and whether the individual is male or female. This paper is an attempt to explain the supposed male vulnerability to COVID-19 using a causal approach. We proceed by identifying a set of confounding and mediating factors, based on the review of epidemiological literature and analysis of sex-dis-aggregated data. Those factors are then taken into consideration to produce explainable and fair prediction and decision models from observational data. The paper outlines how non-causal models can motivate discriminatory policies such as biased allocation of the limited resources in intensive care units (ICUs). The objective is to anticipate and avoid disparate impact and discrimination, by considering causal knowledge and causalbased techniques to compliment the collection and analysis of observational big-data. The hope is to contribute to more careful use of health related information access systems for developing fair and robust predictive models., ERC grant Hypatia under the European Union's Horizon 2020 research and innovation programme 835294, Spanish Government Juan de la Cierva Incorporacion contract IJC2019-039152-I, Google Research Scholar Grant, Marie Sklodowska-Curie Actions (MSCA) Postdoctoral Fellowship 101059332, Universidad de Granada/CBUA

Adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC) are the most frequent histologic subtypes of lung cancer, and both are rich in activated/myofibroblast-like tumor-associated fibroblasts (TAFs). Nintedanib is a potent antifibrotic drug that targets the tumor stroma and is clinically approved to treat advanced lung ADC patients owing to the survival benefits observed in the LUME-1 clinical trial in ADC but not SCC patients. Although the mechanism underlying the ADC-selective therapeutic effects of nintedanib remained poorly understood, we have previously reported that nintedanib abrogates the pro-tumoral traits of the secretome of ADC-TAFs but not SCC-TAFs, suggesting that secreted factor(s) in ADC-TAFs may be implicated. In addition, we recently unveiled an ADC-specific tumor-promoting crosstalk between TAFs and cancer cells driven by TIMP-1 and CD63, whereas others have shown that TIMP-1 is a molecular target of nintedanib. However, it remains unknown if TIMP-1 is involved in the ADC-selective benefits of nintedanib. To address this question, we used patient-derived TAFs obtained with the patient’s informed consent and using protocols approved by the Ethics Committee of the Hospital Clinic. We treated TGF-β1-activated ADC-TAFs and SCC-TAFs with nintedanib and determined the content of TIMP-1 in their conditioned medium by ELISA. Moreover, we used cell-based functional assays and tumor xenografts after knocking-down TIMP-1 in TAFs by siRNA to examine how silencing TIMP-1 altered their response to nintedanib. By analyzing TCGA data and the human protein atlas, we found that TIMP-1 is consistently upregulated in ADC compared to SCC tumors both at the mRNA and protein levels. Moreover, TCGA data revealed that TIMP-1 is increased in tumors compared to paired control tissue in ADC but not SCC. In culture, we observed that TIMP-1 secretion was higher in ADC-TAFs than SCC-TAFs, and that this secretion was downregulated by nintedanib to a larger extent in ADC-TAFs compared to SCC-TAFs. In vivo analyses revealed that ADC cells co-injected with fibroblasts silenced for TIMP-1 as in SCC-TAFs into immunocompromised mice exhibited a less invasive growth pattern compared to tumors bearing control fibroblasts. In addition, we observed that the inhibition of the pro-tumoral secretome of ADC-TAFs elicited by nintedanib was abrogated upon knocking-down TIMP-1 in TAFs both in vitro and in vivo. Collectively, these results reveal that the high secretion of TIMP-1 in ADC-TAFs render them more responsive to nintedanib, whereas the low TIMP-1 secretion of SCC-TAFs may be a major contributor to the selective resistance of SCC patients to nintedanib. Moreover, our results identify TIMP-1 as a promising predictive biomarker of nintedanib responses. Citation Format: Paula Duch, Natalia Díaz-Valdivia, Marta Gabasa, Rafael Ikemori, Frank Hilberg, Noemí Reguart, Derek Radisky, Jordi Alcaraz. Aberrant TIMP-1 secretion by tumor-associated fibroblasts is a major contributor to the selective positive response to nintedanib in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2356.

Las danzas y músicas folklóricas han sido elementos eficaces para dar cuerpo a ideas de nación por medio de la creación de sujetos nacionales que las encarnan y recrean en su práctica, imaginarios y repertorios afectivos. El campo de las danzas tradicionales argentinas se encuentra formado por dos perspectivas: la “académico-tradicional” y la perspectiva “expresivo-vivencial”. Esta última postula una nueva tradición selectiva que posibilita otras narrativas en torno a la construcción de una identidad nacional, y la visibilización de otros cuerpos e imaginarios de género capaces de encarnarlos. Las danzas tradicionales se transforman en populares y se restauran como discursos sociales que hacen eco de otros conocimientos, memorias sociales y sentidos de la identidad. Este modo de concebirlas busca romper con la neutralidad étnica, la homogeneización cultural y la heterosexualidad estática que los modos académicos impusieron a las danzas folklóricas tradicionales.