Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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    International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations

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    Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL, has developed consensus recommendations for clinical procedures and future research on this disease. Patients with RT typically present with a rapid clinical decline, worsening B-symptoms, elevated lactate dehydrogenase, and/or rapidly enlarging lymphadenopathy. Workup should include a positron emission tomography–computed tomography scan for patients with suspected RT. An excisional biopsy should be taken from an accessible lesion, preferably with the highest fluorodeoxyglucose avidity, and analyzed for the presence of aggressive lymphoma. The molecular relationship to the original CLL clone(s) should be defined. Because no effective standard treatment for RT exists, patients should be treated in a clinical trial. Response of both RT and CLL should be assessed at an early time point, and survival end points should be prioritized in trial design. We hope that these recommendations can help to harmonize clinical and translational research and improve outcomes for patients with RT

    Development of biosensors based on cells for real - time environmental monitoring of estrogen and xenoestrogen dispersion and toxicity in water

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    The research focuses on the development of an innovative cell-based biosensor designed for real-time environmental monitoring of estrogenic and xenoestrogenic endocrine-disrupting chemicals (EEDCs) in water. Estrogens and related compounds, even at very low concentrations, pose serious ecological and health risks by interfering with hormonal signalling pathways. Existing analytical techniques, although sensitive and specific, are expensive, time-intensive, and unsuitable for on-site application. To address these limitations, a biosensing platform was engineered using calcium signalling as the core detection mechanism. Living cells were genetically modified to express aequorin, a bioluminescent calcium-sensitive protein, enabling the quantification of intracellular calcium levels. A silicon photomultiplier (SiPM) array was employed for precise detection of the emitted luminescence, and a robust calibration procedure ensured reliable correlation between signal intensity and calcium concentration. By integrating cellular biology, optical detection, and environmental toxicology, the thesis proposes a novel, sustainable, and portable solution for monitoring estrogenic contamination in aquatic environments, in line with recent EU directives on water quality and endocrine disruptor surveillance. The research also includes a six-month industrial placement at ChemiCare, where the candidate refined protocols for calcium signal detection and applied these tools in parallel studies of chemotherapy-induced peripheral neuropathy.The research focuses on the development of an innovative cell-based biosensor designed for real-time environmental monitoring of estrogenic and xenoestrogenic endocrine-disrupting chemicals (EEDCs) in water. Estrogens and related compounds, even at very low concentrations, pose serious ecological and health risks by interfering with hormonal signalling pathways. Existing analytical techniques, although sensitive and specific, are expensive, time-intensive, and unsuitable for on-site application. To address these limitations, a biosensing platform was engineered using calcium signalling as the core detection mechanism. Living cells were genetically modified to express aequorin, a bioluminescent calcium-sensitive protein, enabling the quantification of intracellular calcium levels. A silicon photomultiplier (SiPM) array was employed for precise detection of the emitted luminescence, and a robust calibration procedure ensured reliable correlation between signal intensity and calcium concentration. By integrating cellular biology, optical detection, and environmental toxicology, the thesis proposes a novel, sustainable, and portable solution for monitoring estrogenic contamination in aquatic environments, in line with recent EU directives on water quality and endocrine disruptor surveillance. The research also includes a six-month industrial placement at ChemiCare, where the candidate refined protocols for calcium signal detection and applied these tools in parallel studies of chemotherapy-induced peripheral neuropathy

    Koselleck e la Historik che non scrisse

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    Almost twenty years after the death of Reinhart Koselleck, scholarly interest in his work continues to grow, as evidenced by a wide range of recent critical literature. Stefan-Lud- wig Hoffmann’s recent volume, Der Riss in der Zeit, offers a comprehensive reading of Koselleck’s oeuvre and aims to reconstruct the Historik that was never written. Special attention is devoted to his wartime experience and imprisonment in the Soviet Union, as well as to his intellectual elaboration of Nazism. In the second half of his career, Koselleck favoured the short essay form to develop a conception of history grounded in the intersec- tion of lived experience, political theory, and epistemological reflection. The author criti- cally reconstructs Koselleck’s formative context and intellectual relationships (from Kühn to Schmitt), tracing the evolution of his thought from Kritik und Krise to the maturation of key concepts such as «temporal layers» (Zeitschichten) and «past future» (vergangene Zu- kunft). Hoffmann shows how Koselleck’s «experiential science» came to embrace hetero- dox sources and languages – from psychoanalysis to individual memory – without ever abandoning the rigour of historical method. The volume invites renewed reflection on Koselleck’s contemporary relevance as a critical interpreter of modernity, suggesting that his historiographical legacy, far from being exhausted, remains open to new readings

    Role of Ions in Solvated Amino Acids Raman Spectra

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    Raman spectroscopy is a highly informative technique that is routinely used to analyze the chemical bonds in molecules, such as peptides. However, while Raman spectra of aqueous single amino acids are well-characterized, proteins and peptides are usually found only in solutions in the presence of ions for stability or further analysis. The impact of ions on the Raman spectra of amino acids and subsequently on peptides and proteins has not been systematically studied. In this work, the impact of different metal ions on the Raman spectra of four significant amino acids (glutamate, tyrosine, cysteine, and serine) and N-methylacetamide (a model of a peptide bond) in aqueous solution was studied using density functional theory simulations and Raman spectroscopy experimental validation. The research focused on analyzing band shifts and variations in peak intensity when different cations commonly used in experiments (Li+, Na+, K+, Ag+, Au+, Cu+, and Cu2+) were present. Experimental evidence on Raman spectra variation of Glutamate in the presence of different concentrations of Cu2+ is also provided. Our results show that the ions stay close to the oxygen atoms in the amino acids tested. With regard to Raman spectra, we show Cu2+ promotes Raman resonance. We have characterized and tabulated the shifts in the characteristic Raman peaks of the amino acids in response to metal ions with the aim of providing a reference for interpreting Raman spectra of proteins and other biological materials

    Algorithms for Computing Very Large BWTs: a Short Survey

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    The Burrows-Wheeler Transform (BWT) is a fundamental string transformation that, although initially introduced for data compression, has been extensively utilized across various domains, including text indexing and pattern matching within large datasets. Although the BWT construction is linear, the constants make the task impractical for large datasets, and as highlighted by Ferragina et al. [Paolo Ferragina et al., 2012], "to use it, one must first build it!". Thus, the construction of the BWT remains a significant challenge. For these reasons, during the past three decades there has been a succession of new algorithms for its construction using techniques that work in external memory or that use text compression. In this survey, we revise some of the most important advancements and tools presented in the past years for computing large BWTs exploiting external memory or text compression approaches without using additional information about the data

    Il patrimonio UNESCO nel tempo e nello spazio: territorio, soggetti, esperienze

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    introduzione alla sessione IL PATRIMONIO UNESCO NEL TEMPO E NELLO SPAZIO: TERRITORIO, SOGGETTI, ESPERIENZE, del Convegno "Geografia e patrimonio

    The use of bone-modifying agents in early breast cancer: AIOM Guidelines update and perspectives

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    Breast cancer (BC) is the leading cause of cancer-related mortality among women, with early BC (EBC) comprising most cases. Advancements in neo(adjuvant) therapies have significantly improved outcomes, although they are often associated with cancer treatment-induced bone loss, which increases the risk of fractures and negatively impacts quality of life. Bone-modifying agents (BMAs), such as bisphosphonates and denosumab can mitigate this adverse effect. By reviewing and summarizing the most recent evidence published on BMAs use in EBC, an expert Italian Panel, composed of the authors of the Italian Association of Medical Oncology (AIOM) guidelines, offers an extended clinical interpretation and updated overview of key questions and recommendation, including the optimal timing of BMAs initiation, appropriate treatment duration, and the most effective agents for fracture risk reduction. Additionally, a critical and previously unaddressed topic is also discussed: BMAs impact on survival outcomes in EBC scenario. This paper offers practical insights into bone health management for EBC patients, explores the potential survival benefits offered by BMAs, and highlights differences among international guidelines regarding their recommended use

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