On the Drafts of the Poem "Mr Cogito and the Imagination"

The article subjects to analysis selected motifs from Zbigniew Herbert’s poem “Mr. Cogito and the Imagination” based on the draft copies of the work that are stored in the poet’s archive. An analysis of the manuscripts, which reveals a different, hidden aspect of the final text, allows for the investigation of what was omitted in the process of creation, such as the motif of Daedal and the reference to the Upanishads, and traces the development of the significant themes of the poem: a concept of identity and the notion of tautology

Pracownia pisarska - o brulionach Zbigniewa Herberta

A writer’s manuscripts reveal the text in statu nascendi. They represent the space in which textual identity is constructed, and reveal specific moments of interaction between the writer’s biography and the text. Herbert’s drafts and notes are a space of dialogue with himself and tradition, they contain notes on his reading and shed light on the palimpsestic dimension of the poet’s work. A key phenomenon in the dynamic of writing are the deletions, which can tell us much about the subject and his aesthetic choices. To study the drafts is to broaden the field of interpretation, to pose new questions, to multiply doubts and to unveil the face of Herbert’s work. Fornari draws on French theories of genetic criticism to present these problems with reference to specific examples from the materials in the Zbigniew Herbert archive at the National Library of Poland

Pracownia pisarska - o brulionach Zbigniewa Herberta

A writer’s manuscripts reveal the text in statu nascendi. They represent the space in which textual identity is constructed, and reveal specific moments of interaction between the writer’s biography and the text. Herbert’s drafts and notes are a space of dialogue with himself and tradition, they contain notes on his reading and shed light on the palimpsestic dimension of the poet’s work. A key phenomenon in the dynamic of writing are the deletions, which can tell us much about the subject and his aesthetic choices. To study the drafts is to broaden the field of interpretation, to pose new questions, to multiply doubts and to unveil the face of Herbert’s work. Fornari draws on French theories of genetic criticism to present these problems with reference to specific examples from the materials in the Zbigniew Herbert archive at the National Library of Poland

TP53/MicroRNA interplay in hepatocellular carcinoma

The role of microRNAs as oncogenes and tumor suppressor genes has emerged in several cancers, including hepatocellular carcinoma (HCC). The pivotal tumor suppressive role of p53-axis is indicated by the presence of inactivating mutations in TP53 gene in nearly all cancers. A close interaction between these two players, as well as the establishment of complex p53/miRNAs loops demonstrated the strong contribution of p53-effector miRNAs in enhancing the p53-mediated tumor suppression program. On the other hand, the direct and indirect targeting of p53, as well as the regulation of its stability and activity by specific microRNAs, underlie the importance of the fine-tuning of p53 pathway, affecting the cell fate of damaged/transformed cells. The promising results of miRNAs-based therapeutic approaches in preclinical studies and their entrance in clinical trials demonstrate the feasibility of this strategy in several diseases, including cancer. Molecularly targeted drugs approved so far for HCC treatment show intrinsic or acquired resistances with disease progression in many cases, therefore the identification of effective and non-toxic agents for the treatment of HCC is actually an unmet clinical need. The knowledge of p53/miRNA inter-relations in HCC may provide useful elements for the identification of novel combined approaches in the context of the \u201cpersonalized-medicine\u201d era

MicroRNAs at the Crossroad between Immunoediting and Oncogenic Drivers in Hepatocellular Carcinoma

Treatments aimed to reverse the tumor-induced immune tolerance represent a promising approach for advanced hepatocellular carcinoma (HCC). Notwithstanding, primary nonresponse, early, and late disease reactivation still represent major clinical challenges. Here, we focused on microRNAs (miRNAs) acting both as modulators of cancer cell hallmarks and immune system response. We outlined the bidirectional function that some oncogenic miRNAs play in the differentiation and program activation of the immune system development and, at the same time, in the progression of HCC. Indeed, the multifaceted spectrum of miRNA targets allows the modulation of both immune-associated factors and oncogenic or tumor suppressor drivers at the same time. Understanding the molecular changes contributing to disease onset, progression, and resistance to treatments might help to identify possible novel biomarkers for selecting patient subgroups, and to design combined tailored treatments to potentiate antitumor approaches. Preliminary findings seem to argue in favor of a bidirectional function of some miRNAs, which enact an effective modulation of molecular pathways driving oncogenic and immune-skipping phenotypes associated with cancer aggressiveness. The identification of these miRNAs and the characterization of their 'dual' role might help to unravel novel biomarkers identifying those patients more likely to respond to immune checkpoint inhibitors and to identify possible therapeutic targets with both antitumor and immunomodulatory functions. In the present review, we will focus on the restricted panel of miRNAs playing a bidirectional role in HCC, influencing oncogenic and immune-related pathways at once. Even though this field is still poorly investigated in HCC, it might represent a source of candidate molecules acting as both biomarkers and therapeutic targets in the setting of immune-based treatments

Bias in food intake reporting in children and adolescents with type 1 diabetes: the role of body size, age and gender

An assessment of total daily energy intake is helpful in planning the overall treatment of children with type 1 diabetes (T1D). However, energy intake misreporting may hinder nutritional intervention.Aims: To assess the plausibility of energy intake reporting and the potential role of gender, body mass index (BMI) z-score (z-BMI), disease duration and insulin requirement in energy intake misreporting in a sample of children and adolescents with T1D.Methods: The study included 58 children and adolescents aged 8–16 yr with T1D. Anthropometry, blood pressure and glycated hemoglobin (HbA1c) were measured. Subjects were instructed to wear a SenseWear Pro Armband (SWA) for 3 consecutive days, including a weekend day and to fill out with their parents a weighed dietary record for the same days. Predicted energy expenditure (pEE) was calculated by age and gender specific equations, including gender, age, weight, height and physical activity level (assessed by SWA). The percent reported energy intake (rEI)/pEE ratio was used as an estimate of the plausibility of dietary reporting.Results: Misreporting of food intake, especially under-reporting, was common in children and adolescents with T1D: more than one-third of participants were classified as under- reporters and 10% as over-reporters. Age, z-BMI and male gender were associated with the risk of under-reporting (model R2 = 0.5). Waist circumference was negatively associated with the risk of over-reporting (model R2 = 0.25).Conclusions: Children and adolescents with T1D frequently under-report their food intake. Age, gender and z-BMI contribute to identify potential under-reporters

Multi-level model for the investigation of oncoantigen- driven vaccination effect

BACKGROUND: Cancer stem cell theory suggests that cancers are derived by a population of cells named Cancer Stem Cells (CSCs) that are involved in the growth and in the progression of tumors, and lead to a hierarchical structure characterized by differentiated cell population. This cell heterogeneity affects the choice of cancer therapies, since many current cancer treatments have limited or no impact at all on CSC population, while they reveal a positive effect on the differentiated cell populations. RESULTS: In this paper we investigated the effect of vaccination on a cancer hierarchical structure through a multi-level model representing both population and molecular aspects. The population level is modeled by a system of Ordinary Differential Equations (ODEs) describing the cancer population's dynamics. The molecular level is modeled using the Petri Net (PN) formalism to detail part of the proliferation pathway. Moreover, we propose a new methodology which exploits the temporal behavior derived from the molecular level to parameterize the ODE system modeling populations. Using this multi-level model we studied the ErbB2-driven vaccination effect in breast cancer. CONCLUSIONS: We propose a multi-level model that describes the inter-dependencies between population and genetic levels, and that can be efficiently used to estimate the efficacy of drug and vaccine therapies in cancer models, given the availability of molecular data on the cancer driving force

A mathematical-biological joint effort to investigate the tumor-initiating ability of cancer stem cells.

The involvement of Cancer Stem Cells (CSCs) in tumor progression and tumor recurrence is one of the most studied subjects in current cancer research. The CSC hypothesis states that cancer cell populations are characterized by a hierarchical structure that affects cancer progression. Due to the complex dynamics involving CSCs and the other cancer cell subpopulations, a robust theory explaining their action has not been established yet. Some indications can be obtained by combining mathematical modeling and experimental data to understand tumor dynamics and to generate new experimental hypotheses. Here, we present a model describing the initial phase of ErbB2(+) mammary cancer progression, which arises from a joint effort combing mathematical modeling and cancer biology. The proposed model represents a new approach to investigate the CSC-driven tumorigenesis and to analyze the relations among crucial events involving cancer cell subpopulations. Using in vivo and in vitro data we tuned the model to reproduce the initial dynamics of cancer growth, and we used its solution to characterize observed cancer progression with respect to mutual CSC and progenitor cell variation. The model was also used to investigate which association occurs among cell phenotypes when specific cell markers are considered. Finally, we found various correlations among model parameters which cannot be directly inferred from the available biological data and these dependencies were used to characterize the dynamics of cancer subpopulations during the initial phase of ErbB2+ mammary cancer progression