Addicted or not? A new machine learning-assisted tool for the diagnosis of addiction-like behavior in individual rats

Background: The transition from controlled to compulsive drug use occurs in a small proportion of individuals characterizing substance use disorder (SUD). The "3-Criteria" model developed on the operationalization of key DSM diagnostic criteria of SUD has helped to shed light on behavioural and biological factors involved in these divergent trajectories. However, the classification strategy on which the model has hitherto relied puts as much weight on the cohort to which the individual belongs as on their own characteristics, thereby limiting its construct validity with regards to the individual-based diagnostic approach in humans. Methods: Large datasets resulting from the combination of behavioral data from several of our previous studies on addiction-like behavior for cocaine or alcohol were fed to a variety of machine learning algorithms (each consisting of an unsupervised clustering method combined with a supervised machine learning algorithm) in order to develop a classifier that identifies resilient and vulnerable rats with high precision and reproducibility irrespective of the cohort to which they belong. Results: A classifier based on K-median or K-mean clustering (for cocaine or alcohol, respectively) followed by Artificial Neural Networks emerged as the best tool reliably and accurately to predict if a single rat is vulnerable or resilient to addiction as operationalized in the 3-Criteria model. Thus, all the rats previously characterized as 0 or 3crit in individual cohorts were correctly labelled as Resilient or Vulnerable, respectively, by this classifier. Conclusion: The present machine learning-based classifier objectively labels single individuals as resilient or vulnerable to develop addiction-like behaviour in multisymptomatic preclinical models of cocaine or alcohol addiction in rats, thereby increasing their heuristic value with regards to the human situation.

THE HIGHER HUMANITIES AND SOCIAL-SCIENTIFIC EDUCATION IN A CRISIS - A NEW APPROACH OR A DEAD END? AN ATTEMPT TO UPDATE A “REPLICA“ OF HANS ROBERT JAUSS 'S IDEAS

The article develops two problem areas: The first substantiates the thesis that the basis of the “problems“ of the educational process in higher humanitarian education is not the Covid-19 pandemic crisis. This basis lies in the new historical (“human“) situation of the early 21st century. This situation requires the development of modern theoretical models in the humanities and social sciences and a new “propaedeutic“ model for their study. This new model must reject the traditions of “remembering“ and “reproducing“ a certain amount of information by students and provoke their active participation in the educational process. In addition, views on the “secondary“ and / or even the “death“ of humanitarian and social knowledge are asserted. That is why this study, especially at the university, is somehow isolated within the educational space. The second problematic area deals with the question of the essence, content and heuristic-propaedeutic possibilities of the reflexive synoptic paradigmatic approach. The position that the paradigmatic approach overcomes the extremes of the other two main approaches in the reflective methodology of scientific knowledge: philosophical-methodological historicism and contextualism is defended by uniting them in a new “synoptic“ “philosophical-contextual“ approach. This view does not allow to present the theory and history of humanitarian and social knowledge as the “chronology“ of its existence, nor only as a linear cumulative process of accumulation of ideas or a set of separate “contextual“ analytical texts, but as a “reconstruction“ which presents a theoretical model of the dialectical “becoming“ of the history and theory of humanitarian and social-scientific thought. This model is the means by which the methodological activity and heuristics of the “synoptic“ paradigmatic approach are “verified“, finding expression not only in the elaboration of the general explanatory scheme, but also in revealing the content of the separate theories, which gives huge opportunities for realization not of “reproducing“, but of “mental“, “creative“ research and educational process.

Should Skepticism Be Discredited?

In our day-to-day life and experiences, when one doubts or questions unusually, he is branded a skeptic and consequently resisted. Skeptics, over the years, are seen as people whose basic mood is that of doubt; those who deny absolutely that true knowledge is possible. Although this is not completely true of skepticism, the present work demonstrates, though arguably, that skepticism is more of a philosophical method of inquiry; an epistemological attitude towards knowledge but whose goal is indeed certainty, although it selects a serious doubt concerning all knowledge as the starting point of the inquiry into the possibility of true knowledge. It can rightly be said that the work displays the paradox of skepticism. The word ‘paradox’ originates from a Latin term paradoxum, which has a Greek association paradoxon, or paradoxos, signifying “conflicting with expectation.” Thus, the word paradox signifies a tenet or proposition contrary to received opinions. It is a statement or sentiment that is seemingly contradictory or opposed to common sense and yet, perhaps true in fact. The need for this work is necessitated by the fact that in the present age, it has become no longer the case that the best way to certainty is only by accepting entirely all that one is told, especially when such comes from a sage or a tradition. Obviously, we live in a dispensation where almost every human situation challenges the human rational faculty hence the tendency to change facts and hang-on to lies generates serious fever in every thinking mind. The result of this work therefore is that imperatively, the work demands that whoever wants knowledge should proceed through doubt. The method through which this work arrives at this conclusion is the analytic process of discussion and presentation.

Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

RATIONALITY AND RESPONSIBILITY: BENCHMARKS TO RE-EVALUATE THE LAW IN THE CONTEXT OF THE PANDEMIC CRISIS

Human and social vulnerability in the face of the pandemic once again raises the question of knowledge and of the two key dimensions of the individual (rationality and responsibility) framed in the various relationships they establish (with nature, with other individuals, with state institutions etc.). These become relationships of knowledge and awareness concerning the facts and laws of social-state organization. Being aware that the pandemic crisis left its mark on all areas of life, changing the nature of human relations, affecting the benchmarks of values, and requiring a review of the foundations of social organization, we believe it necessary to assess the current situation through a systemic approach aimed at identifying the benchmarks of the balance between individuality and sociality. Thanks to the assessment of the interdependencies between the individual and the social, the following objectives were addressed: to define the changes caused by the pandemic and analyze the social processes; to validate the decisions taken by the authorities from a logical, praxeological and axiological point of view; to emphasize the importance of norms and principles in the social organization; to determine the role of social actors in overcoming the crisis, and to assess how social relations have evolved under pandemic conditions. Therefore, the present article, applying an interdisciplinary methodology to the pandemic crisis, aims to evaluate, understand and raise awareness of the situation and its impact on the social and human situation, where solidarity, rationality, and human responsibility are being reassessed.

THE RHETORIC OF POLITICAL DISCOURSE: A SIMEO - PRAGMATIC APPROACH

The main step in this research assumes that political discourse should be treated as a convincing speech that pleads the different means of linguistic and non-linguistic argumentations to influence and induce the recipient, where we will discuss political discourse in terms of semiotic and pragmatics behaviors that take it out of a normal nature to a different coding. We will also see it as a new organization of semantic units at the heart of the culture incubating meanings, as accessing and reviving them, but it is done by digging into the memory of the political, and evoking - as much as possible - its cultural dimensions, which can only be done by activating the semantic power. From this perception, everything that is politicized can refer to a particular human situation that is culturally framed, through certain cultural conditions but with the need to know the semantic relationships that allow us to move from direct reporting cases to various possible inspirational and dynamic aspects.

Introduction

The debate between Luther and Erasmus was basically about to what degree, if any, a sinner can freely prepare him/herself for the reception of divine grace. When rejecting the bull of Pope Leo X, Luther had used an exaggerating deterministic or necessitarian theological language which alarmed Erasmus. Erasmus concentrated on the application of God’s grace into the human situation “from below”; Luther, on the contrary, focused on the theocentric nature of grace “from above.” Erasmus promoted the commonly accepted rational view of Late Medieval Catholic soteriology: “to those who do what they can God does not deny his grace,” God’s justice requires that he necessarily grant grace to anyone who freely prepares him/herself to receive it, while Luther spoke the language of Biblical realism: Although human will is free in relation to the natural world, the human being is captivated by the overwhelming power of unfaith, sin, and Satan, being incapable of changing his/her ultimate psychic orientation. In his criticism Luther rehabilitated Augustine’s teaching on the radical limits of human freedom and on the Pneumatological dynamism of divine grace, the view neglected in Medieval theology. Research on Luther’s The Bondage of the Will has not recognized the strong Pneumatological and Trinitarian accent of his theology. Instead, the contradiction between Luther and Erasmus has been explained in philosophical terms such as free will, determinism, necessity, and predestination; this has not revealed the true nature of the profoundly theological conflict between the two “forms of Christianity.” The work at hand makes critical comments on Luther research of the last hundred years and launches the task of a detailed and thorough systematic-theological analysis of the major treatise of Luther.

Making Diabetes Care Fit—Are We Making Progress?

The care of patients with diabetes requires plans of care that make intellectual, practical, and emotional sense to patients. For these plans to fit well, patients and clinicians must work together to develop a common understanding of the patient’s problematic human situation and co-create a plan of care that responds well to it. This process, which starts at the point of care, needs to continue at the point of life. There, patients work to fit the demands of their care plan along with the demands placed by their lives and loves. Thought in this way, diabetes care goes beyond the control of metabolic parameters and the achievement of glycemic control targets. Instead, it is a highly individualized endeavor that must arrive at a care plan that reflects the biology and biography of the patient, the best available research evidence, and the priorities and values of the patient and her community. It must also be feasible within the life of the patient, minimally disrupting those aspects of the patient life that are treasured and justify the pursuit of care in the first place. Patient-centered methods such as shared decision making and minimally disruptive medicine have joined technological advances, patient empowerment, self-management support, and expert patient communities to advance the fit of diabetes care both at the point of care and at the point of life.

Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psycho-Social Stress

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

The situation of the human in the XXI century: globalization challenges and European experience of responses

The paper analyzes the negative impact of technogenic civilization on the development of a human as integrity. The conceptual position of the research is the transdisciplinary idea that a human as integrity is one with all his/her conditions, with the whole world. Giving preference only to the external conditions of a human associated with technical progress led to his/her decline andself-destruction as integrity.The purpose of an investigation consists in showing the reasons of the destruction of human integrity today. Particular attention is paid to the analysis of the modern conditions of human existence associated with the processes of globalization and rapid, negative changes in all spheres of the life of a society in a state of total crisis. It is noted that such conditions chaotize the internal processes of a human, “split” him/her as integrity, destroy the harmonization with other people.Filled with doubts, lacking development prospects and goals, such a human, like the whole society, loses the future.It is concluded that today the human situation is critical. It is necessary to immediately reorient all spheres of life of the society towards human development, harmonization of all his/her essential aspects as integrity. Changes in the public policy, human rights legislation, education and science must be a priority. It is noted that the key role in overcoming the modern anthropological crisis belongs to scientists who, using the EU experience, are able to create a new scientific field for polylogy and the search for optimal ways out of the situation. The transdisciplinary approach, which is actively developed by European transdisciplinary schools and centers, is particularly productive. This approach overcomes the gap between the subject and the object of cognition, between man and the world, and forms a new worldview of man in a new society. Such possibilities of the transdisciplinary approach fully correspond to the tasks of modern universities.