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101 results on '"Ghelli A."'

1. 'La Specola' Museum in Florence: Environmental Monitoring and Building Energy Simulation

Author

Fabio Sciurpi, Leone Pierangioli, and Alessandro Ghelli

Subjects
Engineering, Architectural engineering, business.industry, Technical standard, 02 engineering and technology, Scientific literature, 021001 nanoscience & nanotechnology, 020303 mechanical engineering & transports, 0203 mechanical engineering, Environmental monitoring, HVAC, environmental monitoring, preventing conservation, historical buildings, dynamic simulation, energy model, 0210 nano-technology, business, Building energy simulation, Earth-Surface Processes
Abstract

Among the existing heritage, a specific case is represented by the museums, buildings which need to maintain specific internal environmental conditions for the purpose of preserving the artefacts. In Italy many important museums are in historical buildings that are characterized by inadequate thermal envelope and HVAC system. This paper regards "La Specola" Museum in Florence and analyzes the results obtained from one-year environmental monitoring, undertaken to evaluate the microclimatic conditions of the exposition rooms and showcases considering assessment criteria derived from technical standards and scientific literature. Aim of the research was to create a three-dimensional energy model of the building, calibrated according to commonly used error indexes, and to run a dynamic simulation of their energy behaviour validated by the measured values in the field. The creation of a calibrated energy model of the museum will be useful to evaluate in the future the effectiveness of different strategies (active or passive) for the museum refurbishment.

Published
2020

2. Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia

Author

Pierpaolo Correale, Andrea Ghelli Luserna di Rorà, Francesco Conforti, Gaetanina Golino, Caterina Riillo, Andrea Biondi, Massimo Martino, Giada Juli, Francesca Scionti, Pierfrancesco Tassone, Daniele Caracciolo, Emanuela Altomare, Gabriella Talarico, Eugénie Duroyon, Beatrice Belmonte, Nicoletta Polerà, Ludovic Lhermitte, Chiara Buracchi, Marco Rossi, Vahid Asnafi, Andrea Ballerini, Katia Grillone, Simona Sestito, Markus Hildinger, Greta Alampi, Cirino Botta, Maria Eugenia Gallo Cantafio, Maria Teresa Di Martino, Anna Maria Ferrari, Antonio Giordano, Mariamena Arbitrio, Pierosandro Tagliaferri, Licia Pensabene, Alessandro Gulino, Daniela Concolino, Giovanni Martinelli, Michelangelo Iannone, Claudio Tripodo, Giuseppe Gaipa, Caracciolo, Daniele, Riillo, Caterina, Ballerini, Andrea, Gaipa, Giuseppe, Lhermitte, Ludovic, Rossi, Marco, Botta, Cirino, Duroyon, Eugénie, Grillone, Katia, Gallo Cantafio, Maria Eugenia, Buracchi, Chiara, Alampi, Greta, Gulino, Alessandro, Belmonte, Beatrice, Conforti, Francesco, Golino, Gaetanina, Juli, Giada, Altomare, Emanuela, Polerà, Nicoletta, Scionti, Francesca, Arbitrio, Mariamena, Iannone, Michelangelo, Martino, Massimo, Correale, Pierpaolo, Talarico, Gabriella, Ghelli Luserna di Rorà, Andrea, Ferrari, Anna, Concolino, Daniela, Sestito, Simona, Pensabene, Licia, Giordano, Antonio, Hildinger, Marku, Di Martino, Maria Teresa, Martinelli, Giovanni, Tripodo, Claudio, Asnafi, Vahid, Biondi, Andrea, Tagliaferri, Pierosandro, Tassone, Pierfrancesco, Caracciolo, D, Riillo, C, Ballerini, A, Gaipa, G, Lhermitte, L, Rossi, M, Botta, C, Duroyon, E, Grillone, K, Cantafio, M, Buracchi, C, Alampi, G, Gulino, A, Belmonte, B, Conforti, F, Golino, G, Juli, G, Altomare, E, Polera, N, Scionti, F, Arbitrio, M, Iannone, M, Martino, M, Correale, P, Talarico, G, Di Rora, A, Ferrari, A, Concolino, D, Sestito, S, Pensabene, L, Giordano, A, Hildinger, M, Di Martino, M, Martinelli, G, Tripodo, C, Asnafi, V, Biondi, A, Tagliaferri, P, and Tassone, P

Subjects
Cytotoxicity, Immunologic, Cancer Research, T-Lymphocytes, Mice, SCID, afucosylated monoclonal antibody, Lymphocyte Activation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Epitopes, Jurkat Cells, Antineoplastic Agents, Immunological, Antibody Specificity, Mice, Inbred NOD, antigens, Antibodies, Bispecific, Tumor Microenvironment, Immunology and Allergy, antibodies, hematologic neoplasms, RC254-282, Antibody-dependent cell-mediated cytotoxicity, Leukosialin, bispecific T-cell engagers, medicine.diagnostic_test, biology, hematological malignancie, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.anatomical_structure, antibodie, Oncology, translational medical research, Molecular Medicine, Immunohistochemistry, Female, immunotherapy, Antibody, T-ALL, T-cell engagers, T-cell acute lymphoblastic leukemia, medicine.drug_class, T cell, Immunology, Settore MED/08 - Anatomia Patologica, Monoclonal antibody, Antibodies, Monoclonal, Humanized, Flow cytometry, T Acute Lymphoblastic Leukemia, antigen, Antigen, Phagocytosis, medicine, Animals, Humans, hematological malignancies, Cell Proliferation, Pharmacology, T-cell engager, business.industry, neoplasm, translational research, Basic Tumor Immunology, Xenograft Model Antitumor Assays, Cancer research, biology.protein, business, hematologic neoplasm
Abstract

BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.MethodsUMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal tissue microarrays (TMAs), and by flow cytometry on healthy peripheral blood/bone marrow-derived cells, on 10 different T-ALL cell lines, and on 110 T-ALL primary patient-derived cells. CD43-UMG1 binding site was defined through a peptide microarray scanning. ahuUMG1 was generated by Genetic Glyco-Engineering technology from a novel humanized mAb directed against UMG1 (huUMG1). BTCEs were generated as IgG1-(scFv)2 constructs with bivalent (2+2) or monovalent (2+1) CD3ε arms. Antibody dependent cellular cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and redirected T-cell cytotoxicity assays were analysed by flow cytometry. In vivo antitumor activity of ahUMG1 and UMG1-BTCEs was investigated in NSG mice against subcutaneous and orthotopic xenografts of human T-ALL.ResultsAmong 110 T-ALL patient-derived samples, 53 (48.1%) stained positive (24% of TI/TII, 82% of TIII and 42.8% of TIV). Importantly, no expression of UMG1-epitope was found in normal tissues/cells, excluding cortical thymocytes and a minority (2 log lower as compared with ahuUMG1, with significant mice survival advantage in different T-ALL models in vivo.ConclusionAltogether our findings, including the safe UMG1-epitope expression profile, provide a framework for the clinical development of these innovative immune-therapeutics for this still orphan disease.

Published
2021
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3. Loss of PALB2 predicts poor prognosis in acute myeloid leukemia and suggests novel therapeutic strategies targeting the DNA repair pathway

Author

Andrea Ghelli Luserna di Rorà, Maria Chiara Fontana, Giorgia Simonetti, Giovanni Marconi, Cristina Papayannidis, Antonella Padella, Nicoletta Testoni, Giovanni Martinelli, Torsten Haferlach, Anna Maria Ferrari, Gastone Castellani, Elisabetta Petracci, Eugenio Fonzi, Carmen Baldazzi, Padella A., Fontana M.C., Marconi G., Fonzi E., Petracci E., Ferrari A., Baldazzi C., Papayannidis C., Ghelli Luserna Di Rora A., Testoni N., Castellani G., Haferlach T., Martinelli G., and Simonetti G.

Subjects
Adult, Male, Poor prognosis, DNA Repair, PALB2, Synthetic lethality, Polymorphism, Single Nucleotide, lcsh:RC254-282, Acute myeloid leukaemia, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Text mining, hemic and lymphatic diseases, Correspondence, Cancer genomics, Medicine, Humans, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, business.industry, Myeloid leukemia, Hematology, DNA Repair Pathway, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, synthetic lethality, 3. Good health, Leukemia, Myeloid, Acute, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, business, Fanconi Anemia Complementation Group N Protein, Gene Deletion
Abstract

Dear Editor, Acute myeloid leukemia (AML) patients carrying complex karyotype or aneuploidies have a very poor prognosis, with a 5-year overall survival (OS)

Published
2021

4. Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin

Author

Davide Nappi, Francesco Lanza, Andrea Ghelli Luserna di Rorà, Antonella Padella, Maria Benedetta Giannini, Alessandra Sperotto, Marianna Norata, Claudio Cerchione, Giovanni Martinelli, Giorgia Simonetti, Michele Gottardi, Gerardo Musuraca, Gottardi, Michele, Simonetti, Giorgia, Sperotto, Alessandra, Nappi, Davide, Ghelli Luserna di Rorà, Andrea, Padella, Antonella, Norata, Marianna, Giannini, Maria Benedetta, Musuraca, Gerardo, Lanza, Francesco, Cerchione, Claudio, and Martinelli, Giovanni

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Gemtuzumab ozogamicin, Daunorubicin, CD33, Review, acute myeloid leukemia, Therapeutic targeting, Internal medicine, hemic and lymphatic diseases, Medicine, gemtuzumab ozogamicin, RC254-282, business.industry, Myeloid leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, biomarkers, Minimal residual disease, Multiple drug resistance, Cytarabine, biomarker, business, medicine.drug
Abstract

Simple Summary Gemtuzumab Ozogamicin (GO) is a drug approved for the treatment of acute myeloid leukemia (AML). It targets leukemic cells that express the CD33 molecule on their surface and brings the toxic agent calicheamicin inside the cell to kill it. Several studies have shown that AML patients can benefit of the addition of GO to chemotherapy during induction regimens, pre- and post-transplantation. Moreover, some disease features have been addressed or are under investigation for their capacity to predict response to GO, with the future aim of selecting AML patients that can mostly benefit of GO treatment. Abstract Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic and clinical heterogeneity and high mortality. Despite the recent introduction of novel pharmaceutical agents in hemato-oncology, few advancements have been made in AML for decades. In the last years, the therapeutic options have rapidly changed, with the approval of innovative compounds that provide new opportunities, together with new challenges for clinicians: among them, on 1 September, 2017 the Food and Drug Administration granted approval for Gemtuzumab Ozogamicin (GO) in combination with daunorubicin and cytarabine for the treatment of adult patients affected by newly diagnosed CD33+ AML. Benefits of GO-based regimens were also reported in the pre- and post-transplantation settings. Moreover, several biomarkers of GO response have been suggested, including expression of CD33 and multidrug resistance genes, cytogenetic and molecular profiles, minimal residual disease and stemness signatures. Among them, elevated CD33 expression on blast cells and non-adverse cytogenetic or molecular risk represent largely validated predictors of good response.

Published
2021

5. Combined Oral Fentanyl Citrate and Midazolam as Premedication for Bone Marrow Aspiration and Biopsy in Patients with Hematological Malignancies: A Randomized, Controlled and Patient-Blinded Clinical Trial

Author

Sara Bravaccini, Mattia Altini, Delia Cangini, Marco Picardi, Vincenzo Martinelli, Maria Benedetta Giannini, Giorgia Simonetti, Ilaria Santoriello, Cristiano Minucci, Davide Nappi, Andrea Ghelli Luserna di Rorà, Sonia Ronconi, Aniello Casoria, Claudio Cerchione, Giovanni Martinelli, Fabrizio Pane, Angela Gravetti, Ugo De Giorgi, Novella Pugliese, Cerchione, Claudio, Martinelli, Giovanni, Picardi, Marco, Pugliese, Novella, Nappi, Davide, Casoria, Aniello, Gravetti, Angela, Cangini, Delia, Giannini, Maria Benedetta, Ronconi, Sonia, Simonetti, Giorgia, Ghelli Luserna Di Rorà, Andrea, De Giorgi, Ugo, Altini, Mattia, Bravaccini, Sara, Santoriello, Ilaria, Minucci, Cristiano, Pane, Fabrizio, and Martinelli, Vincenzo

Subjects
anxiolysi, Lidocaine, lcsh:Medicine, Placebo, Article, Sedoanalgesia, anxiolysis, 03 medical and health sciences, 0302 clinical medicine, fentanyl citrate, Biopsy, medicine, Clinical endpoint, pain, 030212 general & internal medicine, medicine.diagnostic_test, business.industry, lcsh:R, analgesia, General Medicine, Clinical trial, 030220 oncology & carcinogenesis, Anesthesia, Midazolam, Premedication, business, bone marrow aspiration and biopsy, medicine.drug
Abstract

Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the routinely used local infiltration anesthesia (LIA) with lidocaine is unable to provide pain relief during the most uncomfortable phases. The primary endpoint of the present randomized, patient-blinded trial was to evaluate the efficacy of an opioid and benzodiazepine combination plus LIA (sedoanalgesia) in patients undergoing BMAB for hematological malignancies. The secondary endpoint was the safety of the procedure in an outpatient setting. Ancillary assessments were anticipatory anxiety related to pain recall in the event of re-biopsy, and adequacy of bone tissue harvested. Patients were randomly assigned to one of 2 arms to receive either sedoanalgesic placebo plus LIA (standard group) or oral fentanyl citrate 200 &mu, g plus oral midazolam 5 mg plus LIA (combo group) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numerical Rating Scale (NRS: 0&ndash, 10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b and T3) and evaluating the degree of discomfort at each time (T) in both groups. One hundred and sixteen patients were eligible for the study. At T2b (time of biopsy) and T3 (time after biopsy), a significantly lower perception of pain was registered in the combo group. Moreover, there were no significant sedoanalgesia-related side-effects. Finally, histological specimens were higher in quality in the combo group. Sedoanalgesia was highly effective in reducing pain during biopsy, diminished anticipatory anxiety in patients undergoing re-biopsy and led to fewer non-diagnostic specimens being harvested.

Published
2020

6. An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia

Author

Sonia Ronconi, Giovanni Martinelli, Giorgia Simonetti, Lucio Catalano, Nicoletta Marra, Sara Bravaccini, Marco Picardi, Ugo De Giorgi, Mauro De Nisco, Mattia Altini, Francesco Pagano, Novella Pugliese, Claudio Cerchione, Adele Bolognese, Silvana Pedatella, Andrea Ghelli Luserna di Rorà, Fabrizio Pane, Michele Manfra, Vincenzo Martinelli, Vita Dora Iula, Cerchione, Claudio, Martinelli, Giovanni, Pedatella, Silvana, De Nisco, Mauro, Pugliese, Novella, Manfra, Michele, Marra, Nicoletta, Ronconi, Sonia, De Giorgi, Ugo, Altini, Mattia, Simonetti, Giorgia, Di Rorà, Andrea Ghelli Luserna, Bravaccini, Sara, Catalano, Lucio, Dora Iula, Vita, Pagano, Francesco, Picardi, Marco, Bolognese, Adele, Pane, Fabrizio, and Martinelli, Vincenzo

Subjects
0301 basic medicine, Drug, Cancer Research, Antimetabolites, Antineoplastic, medicine.drug_class, media_common.quotation_subject, Drug Storage, Fungal contamination, Vial, Antimetabolite, Drug Costs, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Drug Stability, Cost Savings, Pharmaceutical Preparations, acute leukemia,cytarabine, supportive care, Medicine, Humans, Pharmacology (medical), acute leukemia, Patient compliance, Nuclear Magnetic Resonance, Biomolecular, Chromatography, High Pressure Liquid, media_common, Pharmacology, Acute leukemia, Clinical Report, business.industry, Cytarabine, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Solutions, supportive care, Leukemia, Myeloid, Acute, 030104 developmental biology, Oncology, Drug Package, 030220 oncology & carcinogenesis, Anesthesia, business, medicine.drug
Abstract

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

Published
2020

7. Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia

Author

Simona Righi, Valentina Robustelli, Sarah Parisi, Nicoletta Testoni, Maria Vittoria Verga Falzacappa, Chiara Sartor, Cristina Papayannidis, Maria Chiara Abbenante, Timothy J. Yen, Michele Cavo, Andrea Ghelli Luserna di Rorà, Chiara Ronchini, Serena De Matteis, Pier Giuseppe Pelicci, Enrica Imbrogno, Anna Maria Ferrari, Neil Beeharry, Giovanni Marconi, Maria Chiara Fontana, Giovanni Martinelli, Ilaria Iacobucci, Carmen Baldazzi, Elena Sabattini, Stefania Paolini, Ghelli Luserna Di Rorà, Andrea, Beeharry, Neil, Imbrogno, Enrica, Ferrari, Anna, Robustelli, Valentina, Righi, Simona, Sabattini, Elena, Verga Falzacappa, Maria Vittoria, Ronchini, Chiara, Testoni, Nicoletta, Baldazzi, Carmen, Papayannidis, Cristina, Abbenante, Maria Chiara, Marconi, Giovanni, Paolini, Stefania, Parisi, Sarah, Sartor, Chiara, Fontana, Maria Chiara, De Matteis, Serena, Iacobucci, Ilaria, Pelicci, Pier Giuseppe, Cavo, Michele, Yen, Timothy J, and Martinelli, Giovanni

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, T cell, Cell Cycle Proteins, Acute lymphoblastic leukemia, Peripheral blood mononuclear cell, lcsh:RC254-282, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Internal medicine, medicine, Humans, Clofarabine, Molecular Biology, G2/M checkpoint, Hematology, business.industry, lcsh:RC633-647.5, Research, Ponatinib, Nuclear Proteins, lcsh:Diseases of the blood and blood-forming organs, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Protein-Tyrosine Kinases, Chemo-sensitizer agent, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, WEE1 inhibitor, business, Bosutinib, Tyrosine kinase, medicine.drug
Abstract

Background Despite the recent progress that has been made in the understanding and treatment of acute lymphoblastic leukemia (ALL), the outcome is still dismal in adult ALL cases. Several studies in solid tumors identified high expression of WEE1 kinase as a poor prognostic factor and reported its role as a cancer-conserving oncogene that protects cancer cells from DNA damage. Therefore, the targeted inhibition of WEE1 kinase has emerged as a rational strategy to sensitize cancer cells to antineoplastic compounds, which we evaluate in this study. Methods The effectiveness of the selective WEE1 inhibitor AZD-1775 as a single agent and in combination with different antineoplastic agents in B and T cell precursor ALL (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B/T-ALL cell lines and confirmed in primary ALL blasts. Results We showed that WEE1 was highly expressed in adult primary ALL bone marrow and peripheral blood blasts (n = 58) compared to normal mononuclear cells isolated from the peripheral blood of healthy donors (p = 0.004). Thus, we hypothesized that WEE1 could be a rational target in ALL, and its inhibition could enhance the cytotoxicity of conventional therapies used for ALL. We evaluated the efficacy of AZD-1775 as a single agent and in combination with several antineoplastic agents, and we elucidated its mechanisms of action. AZD-1775 reduced cell viability in B/T-ALL cell lines by disrupting the G2/M checkpoint and inducing apoptosis. These findings were confirmed in human primary ALL bone marrow and peripheral blood blasts (n = 15). In both cell lines and primary leukemic cells, AZD-1775 significantly enhanced the efficacy of several tyrosine kinase inhibitors (TKIs) such as bosutinib, imatinib, and ponatinib, and of chemotherapeutic agents (clofarabine and doxorubicin) in terms of the reduction of cell viability, apoptosis induction, and inhibition of proliferation. Conclusions Our data suggest that WEE1 plays a role in ALL blast’s survival and is a bona fide target for therapeutic intervention. These data support the evaluation of the therapeutic potential of AZD-1775 as chemo-sensitizer agent for the treatment of B/T-ALL. Electronic supplementary material The online version of this article (10.1186/s13045-018-0641-1) contains supplementary material, which is available to authorized users.

Published
2018

8. Formaldehyde in Hospitals Induces Oxidative Stress: The Role of GSTT1 and GSTM1 Polymorphisms

Author

Giulia Squillacioti, Federica Ghelli, Marco Panizzolo, Alfredo Santovito, Valeria Bellisario, and Roberto Bono

Subjects
0301 basic medicine, malondialdehyde, Necrosis, Health, Toxicology and Mutagenesis, formaldehyde, 15-F2t-isoprostane, TNFα, GSTT1, GSTM1, occupational health, TP1-1185, Toxicology, medicine.disease_cause, Article, Andrology, 03 medical and health sciences, chemistry.chemical_compound, Exon, 0302 clinical medicine, medicine, Fixative, Chemical Health and Safety, business.industry, Chemical technology, Wild type, Malondialdehyde, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Toxicity, Tumor necrosis factor alpha, medicine.symptom, business, Oxidative stress
Abstract

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A &gt, G), and IL6 (−174, G &gt, C). Workers were ex post split into formalin-employers (57.3 μg/m3) and non-employers (13.5 μg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (&lt, 0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F2t-IsoP (p = 0.027) and MDA (p &lt, 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.

Published
2021

9. Clinical and genetic characteristics of late-onset Huntington's disease

Author

Oosterloo, Mayke, Bijlsma, Emilia K., van Kuijk, Sander MJ., Minkels, Floor, de Die-Smulders, Christine EM., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna-Rita, Biunno, Ida, Bonelli, Raphael M., Bronzova, Juliana, Burgunder, Jean-Marc, Dunnett, Stephen B., Ferreira, Joaquim J., Frich, Jan, Giuliano, Joe, Handley, Olivia J., Heiberg, Arvid, Illarioshkin, Sergey, Illmann, Torsten, Klempir, Jiri, Landwehrmeyer, G. Bernhard, Levey, Jamie, Mclean, Tim, Nielsen, Jørgen E., Koivisto, Susana Pro, Päivärinta, Markku, Pålhagen, Sven, Quarrell, Oliver, Ramos-Arroyo, Maria, Roos, Raymund A. C., Saft, Carsten, Sebastián, Ana Rojo, Tabrizi, Sarah J., Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström+, Jan, Zaremba, Jacek (formerly Rödig, Verena, Baake, Barth, Katrin, Garde, Monica Bascuñana, Becanovic, Kristina, Bernard, Tomáš, Betz, Sabrina, Bos, Reineke, Come, Adrien, Guedes, Leonor Correia, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Horta, Andrea, Hvalstedt, Carina, Held, Christine, Hussain, Hasina, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Münkel, Kristina, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren (formerly Heinonen), Niini, Salgueiro, Ana, Šašinková, Pavla, Seliverstov, Yury, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, van Walsem, Marleen R., Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Hecht, Karen, Herranhof, Brigitte, Holl (formerly Hödl), Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Lilek, Sabine, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Larcher, Barbara, Mahlknecht, Philipp, Müller, Christoph, Pinter, Bernadette, Poewe, Werner, Reiter, Eva-Magdalena, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Ladurner, Gunther, Lilek, Stefan, Sinadinosa, Daniela, Staffen, Wolfgang, Walleczek, Anna Maria, Linder, Christoph, Pirker, Walter, Liessens, Dirk, Calmeyn, Godelinde, Somers, Nele, Delvaux, Isabelle, Boogaerts, Andrea, Flamez, Anja, de Raedt, Sylvie, Alaerts, Nick, Slama, Hichem, Supiot, Frédéric, Constant, Eric, Gillardin, Anne-Françoise, Léonard, Marie-Claude, van de Wyngaerde, Françoise, Dupuis, Michel, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, van Reijen, Dimphna, Weckx, Petra, Kaiserova, Michaela, Šenkárová, Zuzana, Bezdíček, Ondřej, Klempíř, Jiří, Klempířová, Olga, Majerová-Ibarburu, Veronika, Nikolai, Tomáš, Roth, Jan, Stárková, Irena, Madsen, Louise Hasselstrøm, Møller, Anette Torvin, Hjermind, Lena, Jacobsen, Oda, Larsen, Ida Unmack, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Roos, Peter, Stockholm, Jette, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Lolk, Annette, Lundsgaard, Marianne, Wermuth, Lene, Andersson, Christian, Nyberg, Clara, Sundblom, Jimmy, Peippo, Maarit, Sipponen, Marjatta, Bruun, Anu, Hartikainen, Paivi, Mäkipää, Seija, Ollokainen, Mari, Åman, Jaana, Kärppä, Mikko, Ignatius, Jaakko, Jääskeläinen, Outi, Kajula, Outi, Moilanen, Jukka, Mustonen, Aki, Santala, Maire, Eklund, Pia, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Ojala, Marjut, Tähkäpää, Sirkku, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Bled, Déborah, Debruxelles, Sabrina, Duché, Charlotte, Fraisse, Sonia, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Couttier, Julien, Debilly, Bérengère, Delaigue, Christine, Derost, Philippe, Durif, Franck, Germain, Véronique, Legendre, Perrine, Loiseau, Sylvie, Marques, Ana, Ulla, Miguel, Vidal, Tiphaine, Badei, Farideh, Boissé, Marie-Françoise, Boudali, Lotfi, Cleret de Langavant, Laurent, Lemoine, Laurie, Morgado, Graca, Youssov, Katia, Annic, Agnès, Barthélémy, Recka, De Bruycker, Christelle, Cabaret, Maryline, Carette, Anne-Sophie, Carrière, Nicolas, Decorte, Eric, Defebvre, Luc, Delliaux, Marie, Delval, Arnaud, Depelchin, Alizé, Destee, Alain, Dewulf-Pasz, Nelly, Dondaine, Thibaut, Dugauquier, Florence, Dujardin, Kathy, Hopes, Lucie, Krystkowiak, Pierre, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Mutez, Eugénie, Peter, Mireille, Plomhause, Lucie, Sablonnière, Bernard, Simonin, Clémence, Tard, Céline, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Blin, Stéphanie, Chen, Simone, Masmoudi, Kamel, Morin, Gilles, Roussel, Martine, Tir, Mélissa, Schüler, Béatrice, Wannepain, Sandrine, Zouitina, Yassine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Guenam, Aicha, Mundler, Laura, Nguyen, Karine, Benaich, Sandra, Brice, Alexis, Boster, Sarah, Charles, Perrine, Durr, Alexandra, Ewenczyk, Claire, Francisque, Hélène, Jauffret, Céline, Justo, Damian, Kassar, Abdulrahman, Klebe, Stephan, Lesne, Fabien, Milani, Paolo, Monin, Marie-Lorraine, Monnier, Tiffany, Roze, Emmanuel, Tataru, Alina, Tchikviladzé, Maya, Bioux, Sandrine, Bliaux, Evangeline, Girard, Carole, Guyant-Maréchal, Lucie, Hannequin, Didier, Hannier, Véronique, Jourdain, Séverine, Maltête, David, Pouliquen, Dorothée, Anheim, Mathieu, Barun, Nadia, Lagha-Boukbiza, Ouhaid, Longato, Nadine, Marcel, Christophe, Phillipps, Clélie, Rudolf, Gabrielle, Steinmetz, Gisèle, Tranchant, Christine, Wagner, Caroline, Zimmermann, Marie-Agathe, Blondeau, Leily, Calvas, Fabienne, Cheriet, Samia, Delabaere, Helène, Demonet, Jean-François, Marquine, Laurent, Pariente, Jérémie, Pierre, Michèle, Pomies, Elsa, Rolland, Sandrine, Souyris, Corinne, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Beuth, Markus, Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike, Thiel, Silvia, Andrich, Jürgen, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kraus, Peter, Stamm, Christiane, Ganos, Christos, Stubbe, Lars, Tadic, Vera, Tübing, Jennifer, Lange, Herwig, Bosredon, Cecile, Hunger, Ulrike, Löhle, Matthias, Maass, Antonia, Ossig, Christiana, Schmidt, Simone, Storch, Alexander, Wolz, Annett, Wolz, Martin, Kohl, Zacharias, Kozay, Christina, Winkler, Jürgen, Bergmann, Ulrike, Böringer, Regina, Capetian, Philipp, Kammel, Gerit, Lambeck, Johann, Mächtel, Miriam, Meier, Simone, Rijntjes, Michel, Zucker, Birgit, Boelmans, Kai, Goerendt, Ines, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Ribbat+, Michael, Longinus, Bernhard, Möller, Carsten, Bürk, Katrin, Lüsebrink, Antje, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthias, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Vogel, Melanie, Weydt, Patrick, Musacchio, Thomas, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, Difruscolo, Olimpia, Franco, Giovanni, Nuzzi, Angela, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Calandra-Buonaura, Giovanna, Capellari, Sabina, Cortelli, Pietro, Gallassi, Roberto, Poda, Roberto, Scaglione, Cesa, Agosti, Chiara, Barlati, Sergio, Compostella, Silvia, Marchina, Eleonora, Padovani, Alessando, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bertini, Elisabetta, Bartoli, Caterina, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, Bandettini di Poggio, Monica, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Di Maria, Emilio, Tamburini, Tiziano, Albanese, Alberto, Castagliuolo, Simona, Castaldo, Anna, Di Donato, Stefano, Di Bella, Daniela, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Panzeri, Marta, Paridi, Dominga, Soliveri, Paola, Spagnolo, Francesca, Taroni, Franco, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Esposito, Chiara, Martino, Tiziana, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Vezza, Maurizio, Squitieri, Ferdinando, D'Alessio, Barbara, Lovo, Francesca, Bentivoglio, Anna Rita, Bove, Francesco, Catalli, Claudio, Di Giacopo, Raffaella, Fasano, Alfonso, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Loria, Giovanna, Modoni, Anna, Petracca, Martina, Piano, Carla, Chiara, Piccininni, Quaranta, Davide, Romano, Silvia, Soleti, Francesco, Solito, Marcella, Spadaro, Maria, Torlizzi, Flavia, Coarelli, Giulia, Ferraldeschi, Michela, Ristori, Giovanni, van Hout, Monique S. E., van Vugt, Jeroen P. P., Marit de Weert, A., Verhoeven, Marloes, Dekker, Meike, Klooster, Jesper, Leenders, Nico, van Oostrom, Joost, Kremer, Berry, Baake, Verena, van den Bogaard, Simon J. A., Dumas, Eve M., t Hart, Ellen P., Hogenboom, Marye, Jacobs, Milou, Jurgens, Caroline, Kampstra, Anne, Schoonderbeek, Anne, Witjes-Ané, Marie-Noëlle, Duits, Annelien, Waber, Mirella, Verstappen, Carla, Blinkenberg, Ellen Økland, Hauge, Erik, Tyvoll, Hilde, Aaserud, Olaf, Aanonsen, Nils Olaf, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan C., Gørvell, Per F., Haggag, Kathrine, Johannessen, Cecilie Haggag, Retterstøl, Lars, Røsby, Oddveig, Rummel, Jutta, Sikiric, Alma, Stokke, Bodil, van Walsem, Marleen, Wehus, Ragnhild, Arntsen, Vibeke, Bjørnevoll, Inga, Sando, Sigrid Botne, Haug, Marte Gjøl, Størseth, Hanna Haugan, Østern, Rune, Paulsen, Julie, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska – Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anna Bryl, Jacek Anioła, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol (formerly Kalbarczyk), Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski+, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zaremba, Jacek, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Almeida, Manuel, Calado, Ana, Dias, Margarida, Morgado, Joana, Semedo, Cristina, Coelho, Miguel, Magalhães, Andreia, Mendes, Tiago, Neutel, Dulce, Rodrigues, Filipe, Valadas, Anabela, Costa, Cristina, Cardoso, Helena, Santos, Mariana, Cação, Gonçalo, Cavaco, Sara, Damásio, Joana, Fernandes, Joana, Gonçalves, Alexandra, Loureiro, Rui, Moreira, Inês, Magalhães, Marina, Salgado, Paula, Andrade, Carlos, Costa, Andreia, Garrett, Carolina, Gago, Miguel, Guimarães, Joana, Massano, João, Meireles, Joana, Monteiro, Ana, Khasanova, Diana, Zalyalova, Zuleykha, Klyushnikov, Sergey, Sidorova, Olga, Smirnov, Oleg, Antonova, Victoria, Kopishinskaya, Svetlana, Korotysh, Maria, Magzhanov, Rim, Saifullina, Elena, Kurbatov, Sergey, Solis, Pilar, Herrera, Carmen Durán, Moreno, Patrocinio Garcia, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Classen, Serge Jaumà, Dedichá, Nadia Rodríguez, Buongiorno, María Teresa, María, Andrés de la Cerda Santa, Muñoz, Esteban, Santacruz, Pilar, Barbera, Miquel Aguilar, Pardo, Sonia Arribas, Guia, Dolors Badenes, Calzado, Noemi, Hernanz, Laura Casas, Tartari Díaz-Zorita, Juan Pablo, Catena, Judit López, Ferrer, Pilar Quiléz, Carruesco, Gemma Tome, Robert, Misericordia Floriach, Viladrich, Cèlia Mareca, Roca, Elvira, Ruiz Idiago, Jesús Miguel, Riballo, Antonio Villa, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Bojarsky, Jaime Kulisevsky, Pagonabarraga, Javier, Perez, Jesus Perez, Ribosa, Roser, Villa, Carolina, Acera Gil, Maria Angeles, Corrales, Koldo Berganzo, Gomez Esteban, Juan Carlos, González, Amaia, Merino, Beatriz Tijero, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Sánchez, Jesús, Romero, Sandra Gutierrez, Arbelo, José Matías, Malo de Molina, Rocío, Martín, Idaira, Periañez, Juan Manuel, Udaeta, Beatriz, Alonso-Frech, Fernando, Loarte, María del Valle, Barrero, Francisco, Morales, Blas, Frades, Belén, Villanueva, Marina Ávila, Zea Sevilla, Maria Ascension, Fenollar, María del Mar, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Ventura, Marta Fatás, Caldentey, Juan García, Ribas, Guillermo García, García de Yébenes, Justo, López-Sendón Moreno, José Luis, Barral, Verónica Mañanes, Feliz, Cici, García Ruíz, Pedro José, García, Ana, López, Rosa Guerrero, Bárcenas, Antonio Herranz, Martínez-Descals, Asunción, Pueyo, Angel Martínez, Martin, Veronica Puertas, Martínez, Noelia Rodríguez, Montojo, Teresa, Sainz Artiga, María José, Sánchez, Vicenta, Alarcón, María Dolores, Almagro, Carmen Antúnez, Diéguez, Esther, Fortuna, Lorenza, Legaz, Agustina, Manzanares, Salvadora, Muñoz, Juan Marín, Antequera Torres, María Martirio, Perea, Fuensanta Noguera, Vivancos, Laura, González, Sonia, Guisasola, Luis Menéndez, Prieto, Marta Para, Ribacoba, René, Salvador, Carlos, Lozano, Pablo Sánchez, Ramirez, Inés Legarda, Benito, Dolors Moragues, Arques, Penelope Navas, Lopera, Monica Rodriguez, Pastor, Barbara Vives, Gaston, Itziar, Garcia-Amigot, Fermin, Martinez-Jaurrieta, Maria Dolores, Ramos-Arroyo, Maria Antonia, Adarmes, Astrid, Bernal-Escudero, Maravilla, Carrillo, Fátima, Jesús, Silvia, Mir, Pablo, Vargas-González, Laura, Hermoso, Fátima Damas, García Moreno, José Manuel, Jaramillo, Javier Abril, Lucena, Carolina Mendez, Pacheco Cortegana, Eva María, Peña, José Chacón, Redondo, Luis, Sánchez, Violeta Sánchez, Fernandez, Cristina Melgar, Romero Lemos, María Dolores, Mata, Maite Paredes, Casado, Rocío Villagrán, Bosca, Maria, Burguera, Juan Andres, Brugada, Francisco Castera, Millán Salvador, Jose Maria, Vilaplana, Carmen Peiró, Solís, Pilar, Figuerola, Begoña Jeweinat, Palanca, Paloma Millan, Diago, Elena Bellosta, López del Val, Javier, Martinez, Laura Martinez, López, Elena, Høsterey-Ugander, Ulrika, Fredlund, Gunnel, Constantinescu, Radu, Lewin, Kajsa, Neleborn-Lingefjärd, Liselotte, Berglund, Maria, Berglund, Peter, Linnsand, Petra, Petersén, Åsa, Reimer, Jan, Widner, Håkan, Esmaeilzadeh, Mouna, Tedroff, Joakim, Winnberg, Elisabeth, Benaminov, Stanislav, Björnsson, Elisabeth, Merrick, Daniel, Paucar, Martin, Svenningsson, Per, Wallden, Tina, Berglund, Måns, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Ekwall, Camilla, Göller, Marie-Lousie, Johansson, Anders, Niemelä, Valter, Nyholm, Dag, Wiklund, Leif, Koehli, Jessica, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Zaugg, Sabine Weber, Esposito, Federica, Good, Jean-Marc, Paus, Karin, Vingerhoets, Francois, Wider+, Christian, Jung, Hans H., Petersen, Jens A., Ligon-Auer, Maria, Mihaylova, Violeta, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A., Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Harrower, Timothy, Vernon, Nathan, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza (Keylock), Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Haig-Brown, Diane, Craven, Janet, Pallett, Andrew, Simpson, Steve, Weekes, Rebecca, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Barker, Roger A., O'Keefe, Deidre, Gerrtiz (nee Di Pietro), Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Goudie, David, Buchanan, Lindsay, Mcfadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Carrie, Ho, Mcgill, Marie, Porteous, Mary, Pearson, Pauline, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Neumann, Christian, Patterson, Kirsten, Thomson, David, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Brown, Pauline, Burrows, Liz, Fletcher, Amy, Harding, Alison, Harrison, Kaye, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Rowett, Liz, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Gosling (nee Brown), Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thomas, Wild, Edward, Ackermann, Oda, Duport, Sophie, Scott, Adrienne, Stoy, Nicholas, Vaughn, Jenny, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen (formerly Ritchie), Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Lois, Singh, Baldev, Wood, Josh, Knight, Caroline, O'Neill, Mari, Purkayastha, Debasish Das, Nemeth, Andrea H., Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, Donovan, John O., Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Burn, John, Bailey, Wendy, Coleman, Caroline, Majeed, Tahir, Verstraelen (Ritchie), Nicola, Barrett, Wendy, Aileen, Ho, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Taylor, Cat, Tidswell, Katherine, Kipps, Christopher, Mackinnon, Lesley, Agarwal, Veena, Hayward, Elaine, Gunner, Kerry, Harris, Kayla, Anderson, Mary, Heywood, Melanie, Keys, Liane, Smalley, Sarah, El-Nimr, George, Duffell, Allison, Wood, Sue, Kennedy (nee Smith), Karen, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Tan, Louis, Lau, Puay Ngoh, Pica, Emmanuel, Roos, Raymund AC., Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: KIO Kemta (9), Epidemiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, Klinische Genetica, MUMC+: DA KG Polikliniek (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
Male, HD, 0301 basic medicine, Pediatrics, Neurology, Huntingtin Protein/genetics, FEATURES, Disease, Neuropsychological Tests, 0302 clinical medicine, Cognitive Dysfunction/psychology, Medicine, Family history, Postural Balance, Huntington Disease/genetics, Huntingtin Protein, education.field_of_study, Chorea/physiopathology, Huntington's disease, Sensation Disorders/physiopathology, Middle Aged, Dystonia, Settore MED/26 - NEUROLOGIA, Huntington Disease, neurodegenerative disorders, Sensation Disorders, Disease Progression, Female, medicine.symptom, Adult, medicine.medical_specialty, Population, Age of onset, Late-onset Huntington's disease, Geriatrics and Gerontology, Neurology (clinical), 03 medical and health sciences, AGE, Chorea, Humans, Cognitive Dysfunction, education, Dystonia/physiopathology, Gait Disorders, Neurologic/physiopathology, Gait Disorders, Neurologic, business.industry, medicine.disease, Gait, 030104 developmental biology, Trinucleotide Repeat Expansion, business, 030217 neurology & neurosurgery, Balance problems
Abstract

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P

Published
2019

10. The role of phase I, phase II, and DNA-repair gene polymorphisms in the damage induced by formaldehyde in pathologists

Author

Valeria Bellisario, Roberto Bono, Enrico Cocchi, Martina Buglisi, Alfredo Santovito, Giulia Squillacioti, and Federica Ghelli

Subjects
Adult, Male, 0301 basic medicine, DNA Repair, Science, CYP2C19, medicine.disease_cause, Article, 03 medical and health sciences, Exon, XRCC1, GSTP1, 0302 clinical medicine, Formaldehyde, Genetics, Humans, Medicine, Allele, Gene, Carcinogen, Polymorphism, Genetic, Multidisciplinary, business.industry, Middle Aged, Molecular biology, 030104 developmental biology, Risk factors, 030220 oncology & carcinogenesis, Female, business, Health occupations, Biomarkers, Genotoxicity
Abstract

Formaldehyde (FA) is a human carcinogen used as formalin in hospital laboratories. We evaluated its association with human chromosomal aberrations (CAs) and the risk/protective role played by several genetic polymorphisms in this relationship, on a cohort of 57 exposed pathologists vs 48 controls. All subjects were assessed for CAs on peripheral blood lymphocytes and genotyped for the most common cancer-associated gene polymorphisms which could be related with the genotoxic outcome: CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 (G>A), IL10 − 1082 (G>A), IL10 − 819 (C>T) and IL6 − 174 (G>C). Air-FA concentration was assessed through personal samplers. The comparison between pathologists and controls showed a significantly higher CAs frequency in pathologists. Significant positive correlations were found between CAs frequency and air-FA concentration while significant associations were found between variation in CAs frequency and the mutated allele for CYP1A1 exon 7 (A>G), CYP2C19*2 (G>A), GSTT1-positive, GSTM1-positive and XRCC1 (G399A). Our study confirms the role of FA as genotoxicity inductor, even in workers chronically exposed to low air-FA levels and reveals the role played by some genetic polymorphisms in this association, highlighting the importance of individual susceptibility biomarkers assessment in occupational health studies.

Published
2021

11. Oxidative stress induction in woodworkers occupationally exposed to wood dust and formaldehyde

Author

Elena Grignani, Valeria Bellisario, Martina Buglisi, Enrico Bergamaschi, Roberto Bono, Giulia Squillacioti, Giacomo Garzaro, and Federica Ghelli

Subjects
0301 basic medicine, Oxidative Stress Induction, Epidemiology, Population, Formaldehyde, Physiology, Urine, Toxicology, Positive correlation, lcsh:RC963-969, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicine, education, education.field_of_study, business.industry, Research, Confounding, Public Health, Environmental and Occupational Health, Biomonitoring, Wood dust, Occupational hygiene, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, lcsh:Industrial medicine. Industrial hygiene, Occupational exposure, Occupational hygiene, Cotinine, business, Safety Research, Wood dust
Abstract

Background Many workers are exposed to wood dust (WD) and formaldehyde (FA), whose carcinogenic activity is supposed to be oxidative stress-mediated. This study aims to assess to what extent the occupational exposure to WD and FA, albeit within regulatory limits, could result in OS induction in a woodworkers’ population. Methods The sample population consisted of 127 woodworkers from 4 factories and 111 unexposed controls. Individual exposure was assessed by personal air-samplers. Each participant enrolled in the study filled out a questionnaire and provided a urinary sample to quantify OS biomarkers, namely 15-F2t-IsoProstane (15-F2t-IsoP) and 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dGuo). The main confounding factor for OS, i.e. tobacco smoking exposure, was assessed by measuring cotinine in urine samples. Results Woodworkers were exposed to significantly higher amounts of WD and FA as compared to controls (p 2t-IsoP showed statistically significant higher values in woodworkers compared to controls (p = 0.004). A significant, positive correlation was observed between 15-F2t-IsoP and 8-oxo-dGuo (p = 0.005), cotinine (p = 0.05), FA (p p = 0.01); 8-oxo-dGuo was significantly correlated with cotinine (p = 0.001) and WD (p = 0.004). In addition, WD and FA were significantly correlated each other (p Conclusions The study confirms that WD and FA may induce OS in woodworkers, and highlights that even the compliance with occupational exposure limits can result in measurable biological outcomes.

Published
2021

12. An Empirical Study on the 'Usage of Not' in Real-World JSON Schema Documents

Author

Stefanie Scherzinger, Mohamed Amine Baazizi, Giorgio Ghelli, Dario Colazzo, and Carlo Sartiani

Subjects
Computer science, business.industry, Conceptual modeling, Decision problem, computer.software_genre, JSON, Empirical study, JSON Schema, Logical connective, Data modeling, Empirical research, Software, Negation, Schema (psychology), Artificial intelligence, business, computer, Natural language processing, computer.programming_language
Abstract

We study the usage of negation in JSON Schema data modeling. Negation is a logical operator rarely present in type systems and schema description languages, since it complicates decision problems: many software tools, but also formal frameworks for working with JSON Schema, do not fully support negation. This motivates us to study whether negation is actually used in practice, for which aims, and whether it could—in principle—be replaced by simpler operators. We have collected a large corpus of 80k open source JSON Schema documents from GitHub. We perform a systematic analysis, quantify usage patterns of negation, and also qualitatively analyze schemas. We show that negation is indeed used, albeit infrequently, following a stable set of patterns.

Published
2021

13. Asthma-like symptoms and oxidative stress in adults from the GEIRD Cohort

Author

Valeria Bellisario, Roberto Bono, Giuseppe Verlato, Giulia Squillacioti, Federica Ghelli, and Pavilio Piccioni

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cohort, medicine, General Earth and Planetary Sciences, medicine.disease, medicine.disease_cause, business, Oxidative stress, General Environmental Science, Asthma
Published
2021

14. 15-F2t-Isoprostane during the lifespan: from children to middle age

Author

Roberto Bono, Valeria Bellisario, Federica Ghelli, Giulia Squillacioti, and Paola Dalmasso

Subjects
15-F2t-isoprostane, business.industry, General Earth and Planetary Sciences, Medicine, Physiology, business, Middle age, General Environmental Science
Published
2021

16. Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia

Author

Maddalena Raffini, Samantha Bruno, Maria Chiara Fontana, Martina Pazzaglia, Anna Maria Ferrari, Valentina Robustelli, Simona Soverini, Andrea Ghelli Luserna di Rorà, Maria Teresa Bochicchio, Claudia Venturi, Giovanna Prisinzano, Cristina Papayannidis, Lorenza Bandini, Emanuela Ottaviani, Giovanni Marconi, Eugenia Franchini, Chiara Sartor, Giovanni Martinelli, Maria Chiara Abbenante, Antonella Padella, Giorgia Simonetti, Bruno S., Bochicchio M.T., Franchini E., Padella A., Marconi G., Ghelli Luserna Di Rora A., Venturi C., Raffini M., Prisinzano G., Ferrari A., Bandini L., Robustelli V., Pazzaglia M., Fontana M.C., Sartor C., Abbenante M.C., Papayannidis C., Soverini S., Ottaviani E., Simonetti G., and Martinelli G.

Subjects
Acute Myeloid Leukemia, 0301 basic medicine, Genetics, Article Subject, business.industry, Myeloid leukemia, Methylation, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Stop codon, 3. Good health, Frameshift mutation, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, Oncology, CpG site, 030220 oncology & carcinogenesis, DNA methylation, embryonic structures, Missense mutation, Medicine, business, Research Article
Abstract

Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795∗; NM_022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM_022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586_2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862_Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse.

Published
2019
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17. CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia

Author

Paolo Silimbani, Alessandro Cafaro, Delia Cangini, Giorgia Simonetti, Claudio Cerchione, Giovanni Martinelli, Andrea Ghelli Luserna di Rorà, Maria Benedetta Giannini, and Carla Masini

Subjects
Oncology, Antimetabolites, Antineoplastic, medicine.medical_specialty, Myeloid, Anthracycline, Daunorubicin, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Secondary Acute Myeloid Leukemia, Clinical Trials as Topic, business.industry, Age Factors, Cytarabine, Myeloid leukemia, General Medicine, Middle Aged, Clinical trial, Leukemia, Myeloid, Acute, Regimen, medicine.anatomical_structure, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Liposomes, Mutation, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Over the last few years, we assisted to an increasing knowledge about acute myeloid leukemia (AML) pathobiology. However, outcomes remain unsatisfactory particularly for adult patients over 60 years old. Not surprisingly several cases of therapy-related AML (tAML) and secondary AML, both characterized by poorer prognosis, are more common in older population. For several decades initial therapy for AML remained unchanged and typically treatment consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the so-called "7+3" standard regimen. The efforts made by the researchers to improve this standard schedule, have led to only modest improvement in the response rate (RR) but no change in overall survival (OS), until the recent evolution seen with new target specific mutation therapies. In 2017, a new liposomal-encapsulated formulation with daunorubicin and cytarabine (CPX-351) was approved by the US Food and Drug Administration for the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). Based on the findings that ratiometric delivery may be more effective than administration of either drug at their maximum tolerated dose (MTD), CPX-351 was designed to deliver a fixed 5:1 molar ratio of the two molecules historically used in the standard "7+3" regimen, cytarabine and daunorubicin respectively. CPX-351 did show improvements of overall survival compared to traditional "7+3" in newly diagnosed secondary and therapy-related AML in adult patients. However, questions remain regarding how to select across AML patient subgroups to maximize the clinical benefit. Possible future directions include evaluating CPX-351 dose intensification, combining this liposomal formulation with targeted therapies and not least important a better understanding about the mechanism of improved responses in tAML and AML-MRC, two entities recognized to be less chemo-sensitive than other hematologic malignancies. In summary, CPX-351 offers finally something new in the landscape of AML therapy. Herein we will review the rationale behind this new drug product development, the main pharmacological characteristics, and discuss the results of clinical trials that led to its FDA approval at first and by EMA in 2018.

Published
2020

18. Tagraxofusp and anti-CD123 in blastic plasmacytoid dendritic cell neoplasm: a new hope

Author

Delia Cangini, Paolo Silimbani, Maria Benedetta Giannini, Carla Masini, Giovanni Martinelli, Andrea Ghelli Luserna di Rorà, Alessandro Cafaro, Giorgia Simonetti, and Claudio Cerchione

Subjects
Oncology, medicine.medical_specialty, Recombinant Fusion Proteins, Drug Evaluation, Preclinical, Interleukin-3 Receptor alpha Subunit, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Precision Medicine, Adverse effect, Child, Drug Approval, Transaminases, Aged, Drug Labeling, Diphtheria toxin, biology, business.industry, Interleukin, General Medicine, Dendritic Cells, Precision medicine, Prognosis, Thrombocytopenia, Clinical trial, 030220 oncology & carcinogenesis, Hematologic Neoplasms, biology.protein, 030211 gastroenterology & hepatology, Interleukin-3 receptor, Stem cell, Antibody, business, Capillary Leak Syndrome
Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.

Published
2020

19. Gemtuzumab ozogamicin in acute myeloid leukemia: past, present and future

Author

Delia Cangini, Antonella Padella, Claudio Cerchione, Alessandra Sperotto, Maria Benedetta Giannini, Giovanni Martinelli, Giorgia Simonetti, Andrea Ghelli Luserna di Rorà, and Michele Gottardi

Subjects
Oncology, Myeloid, medicine.medical_treatment, CD33, Sialic Acid Binding Ig-like Lectin 3, Drug Evaluation, Preclinical, Drug resistance, Hematopoietic stem cell transplantation, Arsenicals, Mice, 0302 clinical medicine, Antineoplastic Agents, Immunological, Leukemia, Promyelocytic, Acute, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Multicenter Studies as Topic, Drug Approval, media_common, Clinical Trials as Topic, Cytarabine, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, General Medicine, Middle Aged, Gemtuzumab, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Calicheamicins, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.drug, Drug, medicine.medical_specialty, Gemtuzumab ozogamicin, media_common.quotation_subject, Antineoplastic Agents, Tretinoin, 03 medical and health sciences, Chlorides, Internal medicine, medicine, Animals, Humans, Aged, business.industry, Daunorubicin, medicine.disease, Drug Resistance, Neoplasm, business
Abstract

After being in the therapeutic wilderness for several decades, acute myeloid leukemia has been recently thrust into the limelight with a series of drug approvals. Technical refinements in production, genetic manipulation and chemical modification of monoclonal antibodies led to growing interest in antibodies-based treatment strategies. Much of the focus of these efforts in acute myeloid leukemia has been on CD33 as a target. On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin for treatment of relapsed or refractory CD33sup+/supacute myeloid leukemia. This signals a new chapter in the long and unusual story of gemtuzumab ozogamicin, which was the first antibody-drug conjugate approved for human use by the Food and Drug Administration. In this review we have analyzed the history of this drug which, among several mishaps, is experiencing a second youth and still represents a field to be further explored.

Published
2020

20. A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target

Author

Andrea Ghelli Luserna di Rorà, Giorgia Simonetti, Claudio Cerchione, and Giovanni Martinelli

Subjects
0301 basic medicine, Cancer Research, Cell cycle checkpoint, Cell Cycle Proteins, Review, 0302 clinical medicine, PKMYT1, Neoplasms, WEE1 family kinases, biology, Drug Synergism, Tumor suppressor, Chemoradiotherapy, Hematology, lcsh:Diseases of the blood and blood-forming organs, Protein-Tyrosine Kinases, Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasm Proteins, Wee1, Oncology, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Disease Progression, Signal Transduction, DNA Replication, Pseudo-oncogene, DNA repair, DNA damage, Mitosis, Antineoplastic Agents, Pyrimidinones, Protein Serine-Threonine Kinases, lcsh:RC254-282, Genomic Instability, 03 medical and health sciences, medicine, Humans, WEE1, Protein Kinase Inhibitors, Molecular Biology, business.industry, lcsh:RC633-647.5, Tumor Suppressor Proteins, Membrane Proteins, Cancer, Oncogenes, medicine.disease, 030104 developmental biology, Drug Resistance, Neoplasm, Mutation, Cancer cell, biology.protein, Cancer research, Pyrazoles, business
Abstract

The inhibition of the DNA damage response (DDR) pathway in the treatment of cancer has recently gained interest, and different DDR inhibitors have been developed. Among them, the most promising ones target the WEE1 kinase family, which has a crucial role in cell cycle regulation and DNA damage identification and repair in both nonmalignant and cancer cells. This review recapitulates and discusses the most recent findings on the biological function of WEE1/PKMYT1 during the cell cycle and in the DNA damage repair, with a focus on their dual role as tumor suppressors in nonmalignant cells and pseudo-oncogenes in cancer cells. We here report the available data on the molecular and functional alterations of WEE1/PKMYT1 kinases in both hematological and solid tumors. Moreover, we summarize the preclinical information on 36 chemo/radiotherapy agents, and in particular their effect on cell cycle checkpoints and on the cellular WEE1/PKMYT1-dependent response. Finally, this review outlines the most important pre-clinical and clinical data available on the efficacy of WEE1/PKMYT1 inhibitors in monotherapy and in combination with chemo/radiotherapy agents or with other selective inhibitors currently used or under evaluation for the treatment of cancer patients.

Published
2020

21. Improving working conditions and job satisfaction in healthcare. A study concept design on a participatory organizational level intervention in psychosocial risks management

Author

Monica Ghelli, Benedetta Persechino, Matteo Ronchetti, Ivan Marzocchi, Karina Nielsen, Cristina Di Tecco, and Sergio Iavicoli

Subjects
occupational safety and health, Health, Toxicology and Mutagenesis, Applied psychology, job satisfaction, psychosocial risks, work-related stress, working conditions, lcsh:Medicine, Occupational safety and health, Article, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), Surveys and Questionnaires, 0502 economics and business, Health care, Humans, Baseline (configuration management), Occupational Health, Risk Management, business.industry, 05 social sciences, lcsh:R, Public Health, Environmental and Occupational Health, Work Engagement, 030210 environmental & occupational health, Hospitals, Test (assessment), Italy, Research Design, Job satisfaction, business, Psychology, Psychosocial, 050203 business & management, Line management
Abstract

This paper contributes to the literature on organizational interventions on occupational health by presenting a concept study design to test the efficacy of a Participatory Organizational-level Intervention to improve working conditions and job satisfaction in Healthcare. The Participatory Organizational-level Intervention is developed using the Italian methodology to assess and manage psychosocial risks tailored to Healthcare. We added an additional step: evaluation, aiming to examine how the intervention works, what worked for whom and in which circumstances. This ongoing study is conducted in collaboration with two large Italian hospitals (more than 7000 employees). The study design comprises a quasi-experimental approach consisting of five phases and surveys distributed pre- and post-intervention aiming to capture improvements in working conditions and job satisfaction. Moreover, to evaluate the efficacy of the Intervention in terms of process and content, we use a realist evaluation to test Context-Mechanisms-Outcome (CMO) configurations. We collect contextual factors at baseline and during and post-intervention process data on the key principles of line manager support and employees participation. This study is expected to provide insights on methods and strategies to improve working conditions and employees&rsquo, job satisfaction and on national policies in the occupational health framework.

Published
2020

22. Fluid dynamics characterization and thrombogenicity assessment of a levitating centrifugal pump with different impeller designs

Author

Marco Santus, Gianfranco Beniamino Fiore, Paolo Fontanili, Alberto Redaelli, Nicola Ghelli, Simone Vesentini, Marco Corbelli, and Silvia Bozzi

Subjects
Materials science, 0206 medical engineering, Biomedical Engineering, Biophysics, Thrombogenicity, 02 engineering and technology, Computational fluid dynamics, law.invention, 03 medical and health sciences, Impeller, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, law, Fluid dynamics, Cardiopulmonary bypass, Humans, Computer Simulation, Platelet activation, Levitating centrifugal pumps, business.industry, Extracorporeal circulation, Mechanics, Equipment Design, Centrifugal pump, 020601 biomedical engineering, Hydrodynamics, Heart-Assist Devices, Stress, Mechanical, ECMO, business, 030217 neurology & neurosurgery
Abstract

Technical guidelines nowadays recommend and regulate the use Computational Fluid Dynamics (CFD) to assess the performance of medical devices. CFD coupled to blood damage models has emerged as a powerful tool to evaluate the hemocompatibility of blood recirculating devices. The present study is aimed at evaluating the hydrodynamic performance and the thrombogenic potential of two prototypes of magnetically levitating centrifugal pumps. The two devices differ in the impeller configuration - 6-blades vs. 12-blades - and have been designed to be used in Cardiopulmonary Bypass (CPB) circuits during open heart surgery and in Extracorporeal Membrane Oxygenation (ECMO) to support patients with severe cardiac or respiratory failure. The pumps have been modelled using Direct Numerical Simulation coupled to Lagrangian analysis to predict platelet activation due to abnormal shear stress histories. Numerical results have been compared with experimental data in terms of head generation for different working points. Results show that the 6-blades pump has i) smaller stagnation areas, ii) lower stress levels and iii) higher strain rate, resulting in a lower thrombogenic potential, whereas the 12-blade impeller guarantees a more stable performance at high flow rates, suggesting its preferential use for more demanding applications, such as CPB.

Published
2020

23. Cytogenetic effects among workers exposed to formaldehyde. The possible role of some polymorphisms

Author

Alfredo Santovito, Martina Buglisi, Federica Ghelli, Valeria Bellisario, Roberto Bono, and Enrico Cocchi

Subjects
chemistry.chemical_compound, chemistry, business.industry, Immunology, Public Health, Environmental and Occupational Health, Formaldehyde, Medicine, business
Abstract

Background Formaldehyde (FA) is a human carcinogen. It is commonly used in diluted form as formalin. The purpose of this work was to evaluate the frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as a consequence of the exposure to FA in a hospital setting, taking into account the role of some polymorphisms in developing genotoxic damage. Methods CAs and SCEs assays were performed on peripheral blood lymphocytes of 57 pathologists enrolled in Turin hospitals (Italy) and 48 unexposed enrolled as controls. All subjects were genotyped for CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα -308 (G>A), IL10 -1082 (G>A), IL10 -819 (C>T) and IL6 -174 (G>C) gene polymorphisms. Due to the little number of recessive homozygotes, we compared the dominant genotype with the combined group of heterozygotes and recessive homozygotes. Results Among pathologists, the mean value of personal air-FA was 64.2 µg/m3, mean significantly higher (p = 0.000) than controls (19.1 µg/m3). Similarly, pathologists showed significantly higher values of SCEs (p = 0.009) and CAs (p = 0.000) with respect to controls. In the same group, CYP2C19*2 (p = 0.011), XRCC1 (G399A) (p = 0.007), and IL10 (-1082) (p = 0.042) gene polymorphisms influenced the CAS levels, as well as those of CYP1A1 exon 7 (p = 0.010), XPD A751C (p = 0.002), XPC C499T (p = 0.040), and IL10 (-819) (p = 0.005) the levels of SCEs. In control group, CAs resulted significantly lower in CYP1A1 exon 7 dominant homozygotes (p = 0.001). Conclusions Our study confirms the role of FA as an inductor of genotoxicity, even when, daily, workers are exposed to low FA levels. Some genetic polymorphisms seem to have an influence in modulating the effect of FA exposure, highlighting, in occupational health studies, the role of the individual susceptibility. Key messages FA exposure is confirmed to be a genotoxicity inductor even at low concentrations. Some genetic polymorphisms seem to have a role in the modulation of FA exposure-related damage.

Published
2020

24. Axitinib in Ponatinib-Resistant B-Cell Acute Lymphoblastic Leukemia Harboring a T315L Mutation

Author

Andrea Ghelli Luserna di Rorà, Roberto Guariglia, Giovanni Martinelli, Maria Benedetta Giannini, Bianca Serio, Carmine Selleri, Anna Maria Ferrari, Valentina Giudice, and Giorgia Simonetti

Subjects
Oncology, medicine.medical_specialty, axitinib, Salvage therapy, Case Report, acute lymphoblastic leukemia, Philadelphia chromosome, Catalysis, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, ponatinib, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, ABL, business.industry, Organic Chemistry, Ponatinib, General Medicine, medicine.disease, Computer Science Applications, Clinical trial, Axitinib, chemistry, lcsh:Biology (General), lcsh:QD1-999, 030220 oncology & carcinogenesis, Adult Acute Lymphoblastic Leukemia, TKI inhibitor, business, Tyrosine kinase, 030215 immunology, medicine.drug
Abstract

Adult acute lymphoblastic leukemia (ALL) with BCR-ABL1 rearrangement (Philadelphia chromosome, Ph) is a hematological aggressive disease with a fatal outcome in more than 50% of cases. Tyrosine kinase inhibitors (TKIs) targeting the activity of BCR-ABL1 protein have improved the prognosis; however, relapses are frequent because of acquired somatic mutations in the BCR-ABL1 kinase domain causing resistance to first, second and third generation TKIs. Axitinib has shown in vitro and ex vivo activity in blocking ABL1; however, clinical trials exploring its efficacy in ALL are missing. Here, we presented a 77-year-old male with a diagnosis of Ph positive ALL resistant to ponatinib and carrying a rare threonine to leucine (T315L) mutation on BCR-ABL1 gene. The patient was treated with axitinib at 5 mg/twice daily as salvage therapy showing an immediate although transient benefit with an overall survival of 9.3 months. Further dose-finding and randomized clinical trials are required to assess the real efficacy of axitinib for adult Ph positive ALL resistant to third generation TKIs.

Published
2020

25. Formaldehyde, Oxidative Stress, and FeNO in Traffic Police Officers Working in Two Cities of Northern Italy

Author

Giulia Squillacioti, Elena Grignani, Angelo Corsico, Roberto Bono, Amelia Grosso, Federica Ghelli, Valeria Bellisario, and Pavilio Piccioni

Subjects
Male, Health, Toxicology and Mutagenesis, Formaldehyde, lcsh:Medicine, Outdoor workers, 010501 environmental sciences, Dinoprost, Nitric Oxide, medicine.disease_cause, 01 natural sciences, Article, 03 medical and health sciences, chemistry.chemical_compound, Traffic police, Occupational Exposure, Environmental health, medicine, Humans, FeNO, traffic police officers, Cities, Risk factor, Cotinine, 030304 developmental biology, 0105 earth and related environmental sciences, Air Pollutants, 0303 health sciences, business.industry, lcsh:R, public health, Public Health, Environmental and Occupational Health, Police, Northern italy, Oxidative Stress, Breath Tests, Italy, chemistry, Exhaled nitric oxide, formaldehyde, Female, business, Oxidative stress, 15-F2t-isoprostane
Abstract

Personal air formaldehyde (air-FA) was measured as risk factor of airways inflammation and oxidative stress (SO) induction. Overall, 154 police officers were enrolled from two differently urbanised Italian cities, Turin and Pavia. Urinary F2t-isoprostane (15-F2t-IsoP), a prostaglandin-like compound, was quantified as a biomarker of general OS in vivo and fractional exhaled nitric oxide (FeNO) was measured for monitoring local inflammatory processes. Urinary cotinine was quantified as a biomarker of tobacco smoking exposure. Traffic police officers living in Turin showed an increased level of log air-FA (p &lt, 0.001), equal to +53.6% (p &lt, 0.001). Log air-(FA) mean values were 3.38 (C.I. 95% 3.33&ndash, 3.43) and 2.84 (C.I. 95% 2.77&ndash, 2.92) in Turin and Pavia, respectively. Log (air-FA) was higher in &ldquo, outdoor workers&rdquo, (3.18, C.I. 95% 3.13&ndash, 3.24, p = 0.035) compared to &ldquo, indoor workers&rdquo, showing an increase of +9.3%, even controlling for sex and city. The analyses on 15-F2t-IsoP and FeNO, both adjusted for log air-FA, highlighted that OS and inflammation were higher (+66.8%, p &lt, 0.001 and +75%, p &lt, 0.001, respectively) in Turin traffic police officers compared to those from Pavia. Our findings suggest that even low exposures to traffic-related emissions and urbanisation may influence both general oxidative stress levels and local inflammation.

Published
2020

26. Challenges in Checking JSON Schema Containment over Evolving Real-World Schemas

Author

Stefanie Scherzinger, Giorgio Ghelli, Carlo Sartiani, Mohamed Amine Baazizi, Dario Colazzo, and Michael Fruth

Subjects
JSON Schema containment, Computer science, business.industry, Empirical study, JSON, First generation, Open research, Software, Empirical research, Schema (psychology), ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Software engineering, business, computer, computer.programming_language
Abstract

JSON Schema is maturing into the de-facto schema language for JSON documents. When JSON Schema declarations evolve, the question arises how the new schema will deal with JSON documents that still adhere to the legacy schema. This is particularly crucial in the maintenance of software APIs. In this paper, we present the results of our empirical study of the first generation of tools for checking JSON Schema containment which we apply to a diverse collection of over 230 real-world schemas and their altogether 1k historic versions. We assess two such special-purpose tools w.r.t. their applicability to real-world schemas and identify weak spots. Based on this analysis, we enumerate specific open research challenges that are based on real-world problems.

Published
2020

27. Formaldehyde in hospitals can still represent a risk factor. Oxidative stress and GSTT1 polymorphism

Author

Alfredo Santovito, Roberto Bono, Valeria Bellisario, Federica Ghelli, and Martina Buglisi

Subjects
chemistry.chemical_compound, chemistry, business.industry, Immunology, Public Health, Environmental and Occupational Health, Formaldehyde, Medicine, business, medicine.disease_cause, Oxidative stress
Abstract

Background Nurses employed in operating theatres and pathologists are workers professionally exposed to some environmental xenobiotics, such as drugs and formaldehyde (FA). Through experimental and epidemiological studies, both acute and chronic inhalation of FA has been associated with various health effects, including toxicity in the respiratory tract and cancer. The purpose of this study was to evaluate the relationship between occupational exposure to FA and the intensity of oxidative stress (OS). Methods 87 female hospital workers were enrolled in a Turin hospital in Italy. Each subject filled a questionnaire and provided biological samples to measure OS biomarkers: 15-F2t-Isoprostane, malondialdehyde (MDA) and total glutathione content (GSX) in urine and inflammatory mediators and receptors (sIL-6R, VEGF-R2, TNFR1, TNFa, FGF2, CD30, CD27) in blood. All individuals were genotyped for CYP1A1, GSTT1, GSTM1, TNFa, and IL-6 polymorphisms. A personal passive air sampler, worn for a working shift (8h), assessed personal FA exposure. Results Subjects exposed to FA (27%) resulted to have a significant higher amount of 15-F2t-Isop (p = 0.000), MDA (p = 0.000), GSX (p = 0.001) compared with non-exposed workers. FA concentration was positively correlated with prevalence of reported respiratory symptoms (p = 0.004), 15-F2t-Isop (p = 0.044), GSX (p = 0.000), MDA (p = 0.000), FGF2 (p = 0.000), CD27 (p = 0.000) and negatively with sIL-6R (p = 0.001), VEGF-R2 (p = 0.000). A significant reduction was found in GSTT1 positive subjects concerning MDA levels (p = 0.000). The same relationship was found in the control group (b=-2.25; C.I. 0.21 - 0.516; p = 0.06). Conclusions FA exposure is confirmed to be an OS inductor and to be correlated with inflammatory response, highlighting how daily occupational exposure to this air pollutant can result in measurable biological outcomes. Key messages Daily occupational exposure to FA results in a disruption of oxidative status and inflammatory profile. GSTT1 gene polymorphism is able to influence the MDA levels in the control group.

Published
2020

28. The psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects: A systematic review of published studies

Author

Claudia Branchi, Antonella Granieri, Alessandro Marinaccio, Michela Bonafede, Monica Ghelli, Fanny Guglielmucci, Marisa Corfiati, Valentina Rosa, and Sergio Iavicoli

Subjects
Male, Mesothelioma, Lung Neoplasms, review, Behavioural sciences, Cochrane Library, medicine.disease_cause, Asbestos, stress, 03 medical and health sciences, Social support, 0302 clinical medicine, Quality of life (healthcare), Occupational Exposure, Adaptation, Psychological, medicine, Humans, 030212 general & internal medicine, Depression (differential diagnoses), asbestos, mesothelioma, psychological, Public Health, Environmental and Occupational Health, Depression, business.industry, Environmental and Occupational Health, Mesothelioma, Malignant, Social Support, medicine.disease, Mental health, 030220 oncology & carcinogenesis, Quality of Life, Female, Public Health, business, Stress, Psychological, Clinical psychology
Abstract

Background The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people. Methods Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines. Results We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects. Conclusions This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties.

Published
2018

29. Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients

Author

Serena De Matteis, Giovanni Martinelli, Giulia Abbati, Tania Rossi, Roberta Napolitano, Gerardo Musuraca, Daniele Calistri, Chiara Molinari, Pier Paolo Fattori, Andrea Ghelli Luserna di Rorà, Massimiliano Bonafè, Alessandro Lucchesi, Martina Ghetti, Antonio Cuneo, Gian Matteo Rigolin, De Matteis, Serena, Molinari, Chiara, Abbati, Giulia, Rossi, Tania, Napolitano, Roberta, Ghetti, Martina, Di Rorà, Andrea Ghelli Luserna, Musuraca, Gerardo, Lucchesi, Alessandro, Rigolin, Gian Matteo, Cuneo, Antonio, Calistri, Daniele, Fattori, Pier Paolo, Bonafè, Massimiliano, and Martinelli, Giovanni

Subjects
Genetics and Molecular Biology (all), Male, Chronic lymphocytic leukemia, lcsh:Medicine, Adaptive Immunity, Biochemistry, Interleukin-23, T-Lymphocytes, Regulatory, 0302 clinical medicine, Candida albicans, Aged, 80 and over, medicine.diagnostic_test, Gene Expression Regulation, Leukemic, CLL, Effector-like Tregs, Plasticity, Tregs, Biochemistry, Genetics and Molecular Biology (all), General Medicine, Middle Aged, Acquired immune system, Phenotype, Treg, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Effector-like Treg, Cytokines, Female, Immunosuppressive Agents, T cell, chemical and pharmacologic phenomena, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, NO, Flow cytometry, 03 medical and health sciences, Interferon-gamma, Immune system, medicine, Humans, Aged, Innate immune system, business.industry, Research, Gene Expression Profiling, lcsh:R, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Immunity, Innate, Lymphocyte Subsets, Immunology, business, 030215 immunology
Abstract

Background In chronic lymphocytic leukemia (CLL) disease onset and progression are influenced by the behavior of specific CD4+ T cell subsets, such as T regulatory cells (Tregs). Here, we focused on the phenotypic and functional characterization of Tregs in CLL patients to improve our understanding of the putative mechanism by which these cells combine immunosuppressive and effector-like properties. Methods Peripheral blood mononuclear cells were isolated from newly diagnosed CLL patients (n = 25) and healthy volunteers (n = 25). The phenotypic and functional characterization of Tregs and their subsets was assessed by flow cytometry. In vitro analysis of TH1, TH2, TH17 and Tregs cytokines was evaluated by IFN-γ, IL-4, IL-17A and IL-10 secretion assays. The transcriptional profiling of 84 genes panel was evaluated by RT2 Profiler PCR Array. Statistical analysis was carried out using exact non parametric Mann–Whitney U test. Results In all CLL samples, we found a significant increase in the frequency of IL-10-secreting Tregs and Tregs subsets, a significant rise of TH2 IL-4+ and TH17 IL-17A+ cells, and a higher percentage of IFN-γ/IL-10 and IL-4/IL-10 double-releasing CD4+ T cells. In addition, we also observed the up-regulation of innate immunity genes and the down-regulation of adaptive immunity ones. Conclusions Our data show that Tregs switch towards an effector-like phenotype in CLL patients. This multifaceted behavior is accompanied by an altered cytokine profiling and transcriptional program of immune genes, leading to a dysfunction in immune response in the peripheral blood environment of CLL patients. Electronic supplementary material The online version of this article (10.1186/s12967-018-1545-0) contains supplementary material, which is available to authorized users.

Published
2018

30. La strutturazione del servizio di accoglienza in dialisi: effetti dell'attività di accoglienza in dialisi 2014–2016

Author

Elisabetta Ghelli, Tiziana Rabiti, Gabriele Giacomelli, Sabrina Bonini, David Caiani, Simone Bacherini, Ilaria Ricci, Lorenzo Burgio, Angela Mencattelli, Antonella Biagi, Antonella Berti, and Alessandra Sarti

Subjects
lcsh:Internal medicine, business.industry, medicine.medical_treatment, Nursing research, media_common.quotation_subject, Hospitality, Group culture, Relational tools, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Patient care, Nursing, Perception, Data quality, medicine, Pharmacology (medical), lcsh:RC31-1245, Psychology, Set (psychology), business, Dialysis, media_common
Abstract

A nursing research project including a series of qualitative surveys was set up to investigate how a care-team culture of hospitality and the use of some relational tools could, through a structured approach, have positive effects on patients starting the dialysis treatment pathway. A structured hospitality approach addressed to new-entry patients seems to activate important prerequisites for patient care perception. The research showed that the lack of a personally addressed hospitality approach would not be limited to neutral effects but might have harmful effects on patients' self-care attitude as well, producing different patient outcomes, both clinically and in their interaction with the dialysis setting. The will to stimulate self-empowerment and self-esteem seems to be clearly perceived and appreciated by the patients, and this was confirmed by the collected quality data. The evidence emerging from this study tells us that a care-team culture oriented towards valuing hospitality, which in this case had been implemented in various organizational steps and ways, may have positive effects on care outcomes – not only for the individual patient but also the care-team members – by activating a high satisfaction rebound.

Published
2017

31. Effects of a structured hospitality approach in dialysis

Author

Lorenzo Burgio, Antonella Berti, Alessandra Sarti, Gabriele Giacomelli, Antonella Biagi, Ilaria Ricci, Angela Mencattelli, Sabrina Bonini, David Caiani, Simone Bacherini, Elisabetta Ghelli, and Tiziana Rabiti

Subjects
Structure (mathematical logic), Set (abstract data type), Medical education, Hospitality, business.industry, Nursing research, Group culture, General Medicine, Dialysis (biochemistry), business, Psychology
Abstract

A nursing research project including a series of qualitative surveys was set up to investigate how a care-team culture of hospitality and the use of some relational tools could, through a structure...

Published
2017

32. Chromothripsis in acute myeloid leukemia: Biological features and impact on survival

Author

Michele Cavo, Zdenek Racil, Viviana Guadagnuolo, Antonella Padella, Maria Chiara Fontana, Michael Steurer, Michael Doubek, Emanuela Ottaviani, Nicoletta Testoni, Giovanni Marconi, Marco Manfrini, Torsten Haferlach, Carmen Baldazzi, Stefania Paolini, Simona Soverini, Andrea Ghelli Luserna di Rorà, Vincenza Solli, Robert Kralovics, Anna Maria Ferrari, Eugenio Fonzi, Cristina Papayannidis, Eugenia Franchini, Giovanni Martinelli, Lukáš Semerád, Ilaria Iacobucci, Jelena D. Milosevic Feenstra, Giorgia Simonetti, Fontana, Maria Chiara, Marconi, Giovanni, Feenstra, Jelena D. Milosevic, Fonzi, Eugenio, Papayannidis, Cristina, Ghelli Luserna Di Rorá, Andrea, Padella, Antonella, Solli, Vincenza, Franchini, Eugenia, Ottaviani, Emanuela, Ferrari, Anna, Baldazzi, Carmen, Testoni, Nicoletta, Iacobucci, Ilaria, Soverini, Simona, Haferlach, Torsten, Guadagnuolo, Viviana, Semerad, Luka, Doubek, Michael, Steurer, Michael, Racil, Zdenek, Paolini, Stefania, Manfrini, Marco, Cavo, Michele, Simonetti, Giorgia, Kralovics, Robert, and Martinelli, Giovanni

Subjects
0301 basic medicine, Genome instability, Oncology, Adult, Male, medicine.medical_specialty, NPM1, Cancer Research, Adolescent, Ring chromosome, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Young Adult, Internal medicine, Chromosome instability, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Ring Chromosomes, In Situ Hybridization, Fluorescence, Aged, Proportional Hazards Models, Aged, 80 and over, Chromothripsis, Hematology, business.industry, Myeloid leukemia, Adult Acute Myeloid Leukemia, Middle Aged, Prognosis, 3. Good health, Chromosome Banding, Leukemia, Myeloid, Acute, 030104 developmental biology, Treatment Outcome, Anesthesiology and Pain Medicine, Mutation, Female, business, Nucleophosmin
Abstract

Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix??) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p???=???0.002), ELN high risk (HR) (p?????0.001), lower white blood cell (WBC) count (p???=???0.040), TP53 loss, and/or mutations (p???

Published
2017

33. Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia

Author

Neil Beeharry, Chiara Sartor, Valentina Robustelli, Martina Ghetti, Matteo Bocconcelli, Enrica Imbrogno, Roberta Napolitano, Anna Maria Ferrari, Cristina Papayannidis, Giovanni Marconi, Stefania Paolini, Carolina Terragna, Andrea Ghelli Luserna di Rorà, Samantha Bruno, Giorgia Simonetti, Gabriella Chirumbolo, Timothy J. Yen, Giovanni Martinelli, Di Rora A.G.L., Bocconcelli M., Ferrari A., Terragna C., Bruno S., Imbrogno E., Beeharry N., Robustelli V., Ghetti M., Napolitano R., Chirumbolo G., Marconi G., Papayannidis C., Paolini S., Sartor C., Simonetti G., Yen T.J., and Martinelli G.

Subjects
0301 basic medicine, Cancer Research, T cell, Synthetic lethality, acute lymphoblastic leukemia, wee1, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, chk1, synergism, Medicine, Viability assay, CHEK1, Clonogenic assay, Cytotoxicity, business.industry, Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, dna damage response, 030104 developmental biology, medicine.anatomical_structure, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, business
Abstract

Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of the cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability of the cell cycle and induces cell death in rapidly proliferating cells. Exploiting this finding for a possible therapeutic approach has showed efficacy in various solid and hematologic tumors, though not specifically tested in acute lymphoblastic leukemia. Methods: The efficacy of the combination between WEE1 and CHK1 inhibitors in B and T cell precursor acute lymphoblastic leukemia (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the therapeutic strategy was tested in terms of cytotoxicity, induction of apoptosis, and changes in cell cycle profile and protein expression using B/T-ALL cell lines. In addition, the efficacy of the drug combination was studied in primary B-ALL blasts using clonogenic assays. Results: This study reports, for the first time, the efficacy of the concomitant inhibition of CHK1/CHK2 and WEE1 in ALL cell lines and primary leukemic B-ALL cells using two selective inhibitors: PF-0047736 (CHK1/CHK2 inhibitor) and AZD-1775 (WEE1 inhibitor). We showed strong synergism in the reduction of cell viability, proliferation and induction of apoptosis. The efficacy of the combination was related to the induction of early S-phase arrest and to the induction of DNA damage, ultimately triggering cell death. We reported evidence that the efficacy of the combination treatment is independent from the activation of the p53-p21 pathway. Moreover, gene expression analysis on B-ALL primary samples showed that Chek1 and Wee1 are significantly co-expressed in samples at diagnosis (Pearson r = 0.5770, p = 0.0001) and relapse (Pearson r= 0.8919, p = 0.0001). Finally, the efficacy of the combination was confirmed by the reduction in clonogenic survival of primary leukemic B-ALL cells. Conclusion: Our findings suggest that the combination of CHK1 and WEE1 inhibitors may be a promising therapeutic strategy to be tested in clinical trials for adult ALL.

Published
2019

34. Identification of symbol digit modality test score extremes in Huntington's disease

Author

Braisch, U, Muche, R, Rothenbacher, D, Landwehrmeyer, GB, Long, JD, Bentivoglio, AR, Biunno, I, Bonelli, RM, Dunnett, SB, Illmann, T, Levey, J, Ramos-Arroyo, M, Nielsen, JE, Paivarinta, M, Sebastian, AR, Tabrizi, SJ, Vandenberghe, W, Uhrova, T, Come, A, Garde, MB, Betz, S, Capodarca, S, Wildson, SC, da Silva, V, Di Renzo, M, Finisterra, M, Genoves, C, Gilling, M, Handley, OJ, Hvalstedt, C, Koppers, K, Lamanna, C, Laura, M, Descals, AM, Monza, D, Mutze, L, Oehmen, M, Padieu, H, Paterski, L, Koivisto, SP, Rindal, B, Roren, N, Sasinkova, P, Seliverstov, Y, Timewell, E, Cubillo, PT, van Walsem, MR, Witjes-Ane, MN, Yudina, E, Zielonka, E, Zinzi, P, Braunwarth, EM, Brugger, F, Buratti, L, Hametner, EM, Hepperger, C, Holas, C, Hotter, A, Hussl, A, Larcher, B, Mahlknecht, P, Muller, C, Pinter, B, Poewe, W, Seppi, K, Sprenger, F, Wenning, G, Dupuis, M, Minet, C, Ribai, P, Van Paemel, D, Verellen-Dumoulin, C, Klempir, J, Majerova, V, Roth, J, Babiloni, B, Debruxelles, S, Duche, C, Goizet, C, Jameau, L, Lafoucriere, D, Spampinato, U, Bachoud-Levi, AC, Boisse, MF, de Langavant, LC, Lemoine, L, Morgado, G, Youssov, K, Annic, A, Barthelemy, R, De Bruycker, C, Cabaret, M, Carette, AS, Carriere, N, Decorte, E, Defebvre, L, Delliaux, M, Delval, A, Depelchin, A, Destee, A, Dewulf-Pasz, N, Dondaine, T, Dugauquier, F, Dujardin, K, Lemaire, MH, Manouvrier, S, Peter, M, Plomhause, L, Sablonniere, B, Simonin, C, Tard, C, Thibault-Tanchou, S, Vuillaume, I, Bellonet, M, Benoit, A, Blin, S, Courtin, F, Duru, C, Fasquel, V, Godefroy, O, Krystkowiak, P, Mantaux, B, Roussel, M, Tir, M, Schuler, B, Wannepain, S, Azulay, JP, Chabot, C, Delfini, M, Eusebio, A, Fluchere, F, Grosjean, H, Mundler, L, Nowak, M, Bioux, S, Bliaux, E, Girard, C, Guyant-Marechal, L, Hannequin, D, Hannier, V, Jourdain, S, Maltete, D, Pouliquen, D, Blondeau, L, Calvas, F, Cheriet, S, Delabaere, H, Demonet, JF, Pariente, J, Pierre, M, Beuth, M, Gelderblom, H, Priller, J, Pruss, H, Spruth, E, Thiel, S, Ellrichmannberlin, G, Herrmann, L, Hoffmann, R, Kaminski, B, Saft, C, Bosredon, C, Hunger, U, Lohle, M, Maass, A, Ossig, C, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Kohl, Z, Kozay, C, Ullah, J, Winkler, J, Bergmann, U, Boringer, R, Capetian, P, Kammel, G, Lambeck, J, Meier, S, Rijntjes, M, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Heinicke, W, Hidding, U, Munchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Francis, F, Gayde-Stephan, S, Gorzolla, H, Kramer, B, Minschke, R, Schrader, C, Tacik, P, Longinus, B, Lusebrink, A, Muhlau, M, Peinemann, A, Stadtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bechtel, N, Beckmann, H, Bohlen, S, Gopfert, N, Holzner, E, Lange, H, Reilmann, R, Rohm, S, Rumpf, S, Sass, C, Schepers, S, Weber, N, Barth, K, Buck, A, Connemann, J, Ecker, D, Geitner, C, Held, C, Kesse, A, Landwehrmeyer, B, Lezius, F, Lewerenz, J, Nepper, S, Niess, A, Orth, M, Schneider, A, Schwenk, D, Sussmuth, S, Trautmann, S, Weydt, P, Klebe, S, Musacchio, T, Leypold, C, Noth, K, Cormio, C, de Tommaso, M, Franco, G, Sciruicchio, V, Serpino, C, Calandra-Buonaura, G, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Sambati, L, Scaglione, C, Maserati, MS, Agosti, C, Barlati, S, Compostella, S, Marchina, E, Padovani, A, Bertini, E, Ghelli, E, Ginestroni, A, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, AM, Sorbi, S, Abbruzzese, G, di Poggio, MB, Ferrandes, G, Mandich, P, Marchese, R, Tamburini, T, Baake, V, van den Bogaard, SJA, Bos, R, Dumas, EM, t'Hart, EP, Kampstra, A, Roos, RAC, Schoonderbeek, A, Aaserud, O, Bjorgo, K, Borgeod, N, Dramstad, E, Fannemel, M, Frich, JC, Gorvell, PF, Heiberg, A, Lorentzen, E, Retterstol, L, Rosby, O, Sikiric, A, Stokke, B, van Walsem, M, Wehus, R, Bjornevoll, I, Sando, SB, Haug, MG, Storseth, HH, Arntsen, V, Dziadkiewicz, A, Konkel, A, Narozanska, E, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Arkuszewski, M, Blaszczyk, M, Boczarska-Jedynak, M, Ciach-Wysocka, E, Gorzkowska, A, Nska-Myga, BJ, Kaczmarczyk, A, Klodowska-Duda, G, Opala, G, Stompel, D, Banaszkiewicz, K, Bocwinska, D, Bojakowska-Jaremek, K, Dec, M, Grabska, N, Krawczyk, GM, Kubowicz, E, Malec-Litwinowicz, M, Rudzinska, M, Stenwak, A, Szczudlik, A, Szczygiel, E, Wojcik, M, Wasielewska, A, Bryl, JAA, Ciesielska, A, Klimberg, A, Marcinkowski, J, Samara, H, Sempolowicz, J, Sniewski, BW, Zielonka, D, Gogol, A, Janik, P, Jamrozik, Z, Kaminska, A, Kwiecinski, H, Antczak, J, Jachinska, K, Krysa, W, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz-Jarosz, H, Stepniak, I, Sulek, A, Witkowski, G, Zaremba, J, Zdzienicka, E, Ziora-Jakutowicz, K, Januario, C, Julio, F, Guedes, LC, Coelho, M, Finisterra, AM, Ferreira, JJ, Mestre, T, Mendes, T, Rosa, MM, Valadas, A, Kopishinskaya, S, Korotysh, M, Herrera, CD, Moreno, PG, Bas, J, Busquets, N, Calopa, M, Classen, SJ, Dedicha, NR, Buongiorno, MT, Maria, ADS, Munoz, E, Santacruz, P, Barbera, MA, Pardo, SA, Guia, DB, Calzado, N, Hernanz, LC, Diaz-Zorita, JPT, Catena, JL, Ferrer, PQ, Carruesco, GT, Robert, MF, Viladrich, CM, Roca, E, Idiago, JMR, Riballo, AV, Campolongo, A, de Bobadilla, RF, Bojarsky, JK, Martinez-Horta, S, Pagonabarraga, J, Perez, JP, Ribosa, R, Villa, C, Gil, MAA, Corrales, KB, Esteban, JCG, Gonzalez, A, Merino, BT, Cubo, E, Polo, CG, Mariscal, N, Romero, SG, Arbelo, JM, de Molina, RM, Martin, I, Perianez, JM, Udaeta, B, Alonso-Frech, F, Frades, B, Villanueva, MA, Sevilla, MAZ, Frech, FA, Fenollar, MD, Garcia, RGR, Villanueva, C, Bascunana, M, Ventura, MF, Ribas, GG, de Yebenes, JG, Moreno, JLLS, Barral, VM, Ruiz, PJG, Garcia, A, Lopez, RG, Barcenas, AH, Martinez-Descals, A, Martin, VP, Martinez, NR, Artiga, MJS, Sanchez, V, Pueyo, A, Gonzalez, S, Guisasola, LM, Ribacoba, MPPR, Salvador, C, Lozano, PS, Caldentey, JG, Ramirez, IL, Arques, PN, Lopera, MR, Pastor, BV, Gaston, I, Garcia-Amigot, F, Martinez-Jaurrieta, MD, Ramos-Arroyo, MA, Carrillo, F, Redondo, MTC, Mir, P, Gonzalez, LV, Moreno, JMG, Lucena, CM, Pena, JC, Redondo, L, Sanchez, VS, Fernandez, CM, Mata, MP, Lemos, MDR, Bosca, M, Burguera, JA, Vilaplana, FCBCP, Solis, P, Figuerola, BJ, Palanca, PM, Berglund, P, Constantinescu, R, Fredlund, G, Hosterey-Ugander, U, Linnsand, P, Neleborn-Lingefjard, L, Wahlstrom, J, Palhagen, S, Svenningsson, P, Paucar, M, Wallden, T, Ekwall, C, Goller, ML, Sundblom, J, Stebler, Y, Kaelin, A, Romero, I, Schupbach, M, Zaugg, SW, Jung, H, Petersen, J, Auer, M, Mihaylova, V, Vernon, N, Akhtar, S, Crooks, J, Curtis, A, de Souza, J, Piedad, J, Rickards, H, Wright, J, Pallett, A, Coulthard, E, Gethin, L, Hayward, B, Sieradzan, K, Wright, A, Busse, M, Butcher, C, Dunnett, S, Clenaghan, C, Hunt, S, Jones, L, Jones, U, Khalil, H, Minster, S, Owen, M, Price, K, Townhill, J, Rosser, A, Edwards, M, Ho, C, McGill, M, Porteous, M, Pearson, P, Harrower, T, Irvine, S, Brockie, P, Foster, J, Johns, N, McKenzie, S, Rothery, J, Thomas, G, Yates, S, Deith, C, Ireland, J, Ritchie, S, Andrew, A, Frost, J, Noad, R, Cosgrove, J, Gallantree, D, Hamer, S, Hobson, E, Jamieson, S, Kraus, A, Longthorpe, M, Markova, I, Musgrave, H, Peacy, C, Raman, A, Rowett, L, Toscano, J, Wild, S, Yardumian, P, Clayton, C, Dipple, H, Freire-Patino, D, Hallam, C, Middleton, J, Alusi, S, Davies, R, Foy, K, Gerrans, E, Leggett, H, Pate, L, Anjum, U, Coebergh, J, Eddy, C, McEntagart, M, Patton, M, Peterson, M, Rose, S, Andrews, T, Brown, S, Bruno, S, Doherty, K, Golding, C, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Bek, J, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Johnson, L, Jones, M, Krishnamoorthy, A, Murphy, H, Oughton, E, Partington-Jones, L, Rogers, D, Sollom, A, Snowden, J, Stopford, C, Thompson, J, Tinkler, P, Trender-Gerhard, I, Verstraelen, N, Westmoreland, L, Cass, G, Davidson, L, Davison, J, Fullerton, N, Holmes, K, Komati, S, McDonnell, S, Mohammed, Z, Morgan, K, Savage, L, Singh, B, Wood, J, Chu, E, Knight, C, O'Neill, M, Das Purkayastha, D, Nemeth, AH, Siuda, G, Valentine, R, Dixon, K, Armstrong, R, Harrison, D, Hughes, M, Large, S, Donovan, JO, Palmer, A, Parkinson, A, Soltysiak, B, Timings, L, Williams, J, Burn, J, Weekes, R, Craven, J, Bailey, W, Coleman, C, Haig-Brown, D, Simpson, S, Hare, M, Majeed, T, Bandmann, O, Bradbury, A, Fairtlough, H, Fillingham, K, Foustanos, I, Gill, P, Kazoka, M, Nevitt, L, Peppa, N, Quarrell, O, Taylor, C, Tidswell, K, O'Donovan, K, Agarwal, V, Anderson, M, Gunner, K, Harris, K, Hayward, E, Heywood, M, Keys, L, Kipps, C, MacKinnon, L, Smalley, S, Gowers, L, Powell, K, Bethwaite, P, Edwards, R, Fuller, K, Phillips, M, Tan, L, Burgunder, JM, Lau, PN, Pica, E, Shoulson, I, Gusella, JG, Antonijevic, I, vankammen, D, Foroud, T, Warner, J, Giuliano, J, Vetter, L, Marshall, F, Marder, K, Frucht, S, Moskowitz, C, Clouse, R, Wasserman, P, Shannon, K, Jaglin, J, Jankovic, J, Palao, A, Harrison, M, Singer, C, Quesada, M, Hersch, S, Rosas, D, Tanev, K, Malarick, K, Colcher, A, Sanchez-Ramos, J, Kostyk, S, Paulsen, J, Perlmutter, J, Tabbal, S, Ross, C, Dorsey, R, Nucifora, F, Dubinsky, R, Dubinsky, H, Suchowersky, O, Klimek, ML, Jones, R, Morgan, J, Mohlo, E, Kang, U, Agarwal, P, Factor, S, Jennings, D, Higgins, D, Adams, J, Frank, S, Saint-Hilaire, M, Diggin, M, Furtado, S, Walker, F, O'Neill, C, Quaid, K, LeDoux, M, Raymond, L, Leavitt, B, Decolongon, J, Perlman, S, Peavy, G, Goldstein, J, Kumar, R, McCusker, E, Griffith, J, Loy, C, Wheelock, V, Tempkin, T, Martin, A, Nance, M, Mallonee, W, Suter, G, Revilla, F, Gartner, M, Drazinic, C, Fitzpatrick, MJ, Panisset, M, Duff, K, Scott, B, Weiner, W, Robottom, B, Chiu, E, Yastrubetskaya, O, Churchyard, A, Greenamyre, TJ, Oakes, D, Beck, C, Robertson, S, Eaton, K, Lindsay, P, Deuel, L, MacDonald, M, Hickey, C, Muratori, L, Leserman, A, Doucette, N, Uc, E, Rodnitzky, R, Vik, S, Davis, R, Dietrich, S, Segro, V, Erickson, D, Hunt, V, Lucarelli, N, Broyles, J, Delarosa, J, Louis, E, Panegyres, P, Schmidt, A, Barton, S, Sperin, E, Testa, C, Thiede, F, Zauber, SE, McInnis, R, Welsh, C, Wesson, M, Coleman, A, and European Commission

Subjects
Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, COHORT, Cox hazard model, quantile regression, REGISTRY, symbol digit modalities test, Genotype, Neuropsychological Tests, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, Huntington's disease, Rating scale, mental disorders, medicine, Humans, Verbal fluency test, Longitudinal Studies, Genetics (clinical), Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, Proportional hazards model, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, nervous system diseases, Psychiatry and Mental health, Huntington Disease, Phenotype, Test score, Cohort, Disease Progression, Female, Observational study, business, 030217 neurology & neurosurgery, Stroop effect, Clinical psychology
Abstract

REGISTRY Investigators of the European Huntington's Disease Network and COHORT Investigators of the Huntington Study Group., Studying individuals with extreme phenotypes could facilitate the understanding of disease modification by genetic or environmental factors. Our aim was to identify Huntington's disease (HD) patients with extreme symbol digit modality test (SDMT) scores. We first examined in HD the contribution of cognitive measures of the Unified Huntington's Disease Rating Scale (UHDRS) in predicting clinical endpoints. The language-independent SDMT was used to identify patients performing very well or very poorly relative to their CAG and age cohort. We used data from REGISTRY and COHORT observational study participants (5,603 HD participants with CAG repeats above 39 with 13,868 visits) and of 1,006 healthy volunteers (with 2,241 visits), included to identify natural aging and education effects on cognitive measures. Separate Cox proportional hazards models with CAG, age at study entry, education, sex, UHDRS total motor score and cognitive (SDMT, verbal fluency, Stroop tests) scores as covariates were used to predict clinical endpoints. Quantile regression for longitudinal language-independent SDMT data was used for boundary (2.5% and 97.5% quantiles) estimation and extreme score analyses stratified by age, education, and CAG repeat length. Ten percent of HD participants had an extreme SDMT phenotype for at least one visit. In contrast, only about 3% of participants were consistent SDMT extremes at two or more visits. The thresholds for the one-visit and two-visit extremes can be used to classify existing and new individuals. The identification of these phenotype extremes can be useful in the search for disease modifiers., This work was in part funded by a grant from the EuropeanCommission under the 7th framework programme (RD-Connect, grantagreement number 305444).

Published
2019

35. Assessing objective and verifiable indicators associated with work-related stress: Validation of a structured checklist for the assessment and management of work-related stress

Author

Claudio Barbaranelli, Matteo Ronchetti, Valerio Ghezzi, Benedetta Persechino, Monica Ghelli, Roberta Fida, Sergio Iavicoli, and Cristina Di Tecco

Subjects
Applied psychology, multi-method approach, lcsh:BF1-990, Context (language use), Sample (statistics), Workers' compensation, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, 0502 economics and business, Health care, Criterion validity, Psychology, General Psychology, Original Research, business.industry, 05 social sciences, risk assessment, formative indicators, 030210 environmental & occupational health, checklist, work-related stress, Checklist, lcsh:Psychology, Risk assessment, business, 050203 business & management
Abstract

Risk assessment represents an essential part of any successful intervention in health and safety at work. The most prominent European methodologies propose multi-method approaches for identifying the risks associated with work-related stress. Nevertheless, the most widely used method is the self-administered questionnaire. By adapting the UK Management Standards approach, the Italian National Workers Compensation Authority (INAIL) developed a checklist for the assessment of objective and verifiable indicators of work-related stress. This checklist is filled in by a steering group composed of homogenous groups of workers. Through a web-platform developed by INAIL, a considerable amount of data over the last 5 years has been collected throughout Italy. The aims of this study are to examine the psychometric properties as well as the practical validity of the checklist in a wide sample of Italian companies. The sample comprised 5,301 homogeneous groups of workers nested within 1,631 organizations. The checklist measures two main areas: (1) the organizational indicators of work-related stress (sentinel events) and (2) four and six factors related respectively to content and context of work. Multilevel and multivariate analyses revealed that the checklist shows adequate factor structure and criterion validity. Results also demonstrate that small companies and the public and healthcare sector show higher risk levels. These results support the use of the checklist as a structured and generalizable tool for assessing and monitoring the risks associated with work-related stress.

Published
2018

36. The Combination of the PARP Inhibitor Rucaparib and 5FU Is an Effective Strategy for Treating Acute Leukemias

Author

Giovanni Martinelli, Andrea Ghelli Luserna di Rorà, Klaus-Michael Debatin, Francesco Bertolini, Chiara Ronchini, Lüder Hinrich Meyer, P G Pelicci, Mario Faretta, Ilaria Iacobucci, Stefania Orecchioni, Maria Vittoria Verga Falzacappa, Falzacappa, Maria Vittoria Verga, Ronchini, Chiara, Faretta, Mario, Iacobucci, Ilaria, Ghelli Luserna Di Rorà, Andrea, Martinelli, Giovanni, Meyer, Lüder Hinrich, Debatin, Klaus-Michael, Orecchioni, Stefania, Bertolini, Francesco, and Pelicci, Pier Giuseppe

Subjects
DNA Replication, Male, Antimetabolites, Antineoplastic, Cancer Research, Xenograft Model Antitumor Assay, Indoles, DNA Repair, Cell Survival, DNA repair, DNA damage, Poly ADP ribose polymerase, Apoptosis, Poly(ADP-ribose) Polymerase Inhibitors, Pharmacology, Poly(ADP-ribose) Polymerase Inhibitor, Mice, chemistry.chemical_compound, Cell Line, Tumor, Animals, Humans, Medicine, Neoplasm, Rucaparib, Leukemia, Animal, business.industry, Medicine (all), Apoptosi, Myeloid leukemia, Drug Synergism, medicine.disease, Xenograft Model Antitumor Assays, Disease Models, Animal, Oncology, chemistry, Indole, Drug Resistance, Neoplasm, PARP inhibitor, Female, Fluorouracil, business, Human, DNA Damage
Abstract

The existing treatments to cure acute leukemias seem to be nonspecific and suboptimal for most patients, drawing attention to the need of new therapeutic strategies. In the last decade the anticancer potential of poly ADP-ribose polymerase (PARP) inhibitors became apparent and now several PARP inhibitors are being developed to treat various malignancies. So far, the usage of PARP inhibitors has been mainly focused on the treatment of solid tumors and not too much about their efficacy on leukemias is known. In this study we test, for the first time on leukemic cells, a combined therapy that associates the conventional chemotherapeutic agent fluorouracil (5FU), used as a source of DNA damage, and a PARP inhibitor, rucaparib. We demonstrate the efficacy and the specificity of this combined therapy in killing both acute myeloid leukemia and acute lymphoid leukemia cells in vitro and in vivo. We clearly show that the inhibition of DNA repair induced by rucaparib is synthetic lethal with the DNA damage caused by 5FU in leukemic cells. Therefore, we propose a new therapeutic strategy able to enhance the cytotoxic effect of DNA-damaging agents in leukemia cells via inhibiting the repair of damaged DNA. Mol Cancer Ther; 14(4); 889–98. ©2015 AACR.

Published
2015

37. CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Author

Barbara Loteta, Tiziana Moscato, Michela Ceccolini, Sonia Ronconi, Iolanda Vincelli, Massimo Martino, Giorgia Simonetti, Giovanni Martinelli, Caterina Alati, Massimiliano Mazza, Andrea Ghelli Luserna di Rorà, Virginia Naso, Filippo Antonio Canale, Gaetana Porto, Claudio Cerchione, Gerardo Musuraca, and Fabio Nicolini

Subjects
0301 basic medicine, Oncology, Cart, relapsed multiple myeloma, refractory myeloma, Cancer Research, medicine.medical_specialty, CAR T, Review, Disease, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, neurologic toxicity, Adverse effect, RC254-282, Multiple myeloma, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cytokine release syndrome, medicine.disease, Chimeric antigen receptor, BCMA, multiple myeloma, Cytokine release syndrome, 030104 developmental biology, 030220 oncology & carcinogenesis, Treatment strategy, business
Abstract

Simple Summary Available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CAR T therapy is safety. Cytokine release syndrome (CRS) and neurologic toxicity are well-described adverse effects. In MM trials, most CRS events tended to be grade 1 or 2. Another critical point is the extended timeline of the manufacturing process and that only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise. Abstract Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.

Published
2021

38. Prognostic significance of alterations of pathways regulating autophagy in acute myeloid leukemia

Author

Giovanni Marconi, Maria Chiara Fontana, Cristina Papayannidis, Antonella Padella, Silvia Lo Monaco, Maria Chiara Abbenante, Chiara Sartor, Luca Bertamini, Jacopo Nanni, Andrea Ghelli Luserna di Rorà, Valentina Robustelli, Elena Tenti, Eugenio Fonzi, Giorgia Simonetti, Emanuela Ottaviani, Carmen Baldazzi, Nicoletta Testoni, Giovanni Martinelli, Marconi, Giovanni, Fontana, MARIA CHIARA, Papayannidis, Cristina, Padella, Antonella, LO MONACO, Silvia, Abbenante, Mariachiara, Sartor, Chiara, Bertamini, Luca, Nanni, Jacopo, GHELLI LUSERNA DI RORÀ, Andrea, Robustelli, Valentina, Tenti, Elena, Fonzi, Eugenio, Simonetti, Giorgia, Ottaviani, Emanuela, Baldazzi, Carmen, Testoni, Nicoletta, and Martinelli, Giovanni

Subjects
0301 basic medicine, Cancer Research, Leukemia, business.industry, Mechanism (biology), Autophagy, Cancer, Myeloid leukemia, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, Medicine, Treatment resistance, business
Abstract

7038 Background: Nowadays, science is debating if autophagy in cancer can lead to therapy resistance or it can favor apoptosis. Autophagy pathways are involved pro-apoptotic mechanism, or they can improve stresses survival eliminating damaged mitochondria and proteins. Levels and activity of pro-apoptotic and anti-apoptotic proteins (eg. bcl-2 and p53), high levels of cAMP, and a pink/park complex could play as fulcrum on this lever. Our study aims to define the role of autophagy in AML. Methods: We analyzed 148 consecutive non M3 AML with Affymetrix SNP array. We screened all patients for TP53, FLT3, NMP1 mutations. Patients was treated with intensive induction chemotherapy regimens. Survival data were collected prospectively, with a median follow-up of 18 months. Results: Autophagy alteration (gene group 1: ULK1 CHR11; ULK1 CHR17; BECN1; ATG14; AMBRA1; UVRAG; ATG9A; ATG9B; PIK3C3; PIK3R4) was related to lower Complete Remission rate (CR%) after induction in univariate (p < .001) and multivariable regression model with age, karyotype, secondary AML, TP53 mutation (p = .014); autophagy alteration shown to confer worst Overal Survival (OS) (p < .001) and was significantly associated with complex karyotype and TP53 mutation (p < .001). We detected significant differences in term of survival independently both in gain and loss in group 1 genes (p < .001). Alterations in genes in cAMP pathway (group 2: SESN1; PRKAA1 CHR 3; PRKAB1: PRKAA1 CHR 1: PRKAG1 CHR11; PRKAG1 CHR 7; PRKAG3; PRKAB1) and in genes that could be related to a switch from a physiological role of autophagy to a resiliency mechanism (group 3: CCND1; BCL2; PINK1; PARK2; TP53; MDM1; MDM4) showed to confer worst OS (p < .001 in both groups); Alteration in group 2 and group 3 were related to lower CR% after induction (p < .001 in both groups). Whole Exome Sequencing on 56 patients in our set did not found any significant mutation in genes we analyzed with the exception of TP53. Conclusions: Alterations in autophagy regulator genes are associated with poor prognosis and therapy resistance. A loss in autophagy could block apoptosis, a gain could confer cell resiliency. Acknowledgements: ELN, AIL, AIRC, Progetto Regione-Università 2010-12,FP7 NGS-PTL, HARMONY

Published
2017

39. Deficient necroptosis pathway as a negative prognostic factor in acute myeloid leukemia

Author

Antonella Padella, Sarah Parisi, Carmen Baldazzi, Eugenio Fonzi, Nicoletta Testoni, Giovanni Marconi, Maria Chiara Fontana, Valentina Robustelli, Cristina Papayannidis, Luca Bertamini, Anna Maria Ferrari, Andrea Ghelli Luserna di Rorà, Silvia Lo Monaco, Jacopo Nanni, Eugenia Franchini, Giovanni Martinelli, Emanuela Ottaviani, Stefania Paolini, Maria Chiara Abbenante, Giorgia Simonetti, LO MONACO, Silvia, Marconi, Giovanni, Fontana, MARIA CHIARA, Papayannidis, Cristina, Fonzi, Eugenio, Baldazzi, Carmen, Testoni, Nicoletta, Ottaviani, Emanuela, Franchini, Eugenia, Ferrari, Anna, Simonetti, Giorgia, Padella, Antonella, GHELLI LUSERNA DI RORÀ, Andrea, Robustelli, Valentina, Paolini, Stefania, Abbenante, Mariachiara, Parisi, Sarah, Nanni, Jacopo, Bertamini, Luca, and Martinelli, Giovanni

Subjects
Cancer Research, Prognostic factor, Tumor biology, business.industry, Necroptosis, Myeloid leukemia, Necrotic cell, Oncology, Interferon, Transcription (biology), medicine, Cancer research, Receptor, business, Gene, medicine.drug
Abstract

11611 Background: Necroptosis is a type of necrotic cell death involving several genes transcription and activation of molecular mechanisms as death receptors, interferon, toll-like receptors, intracellular RNA and DNA sensors.The process is leading by the family of receptor-interacting protein kinase ( RIPK3, RIPK2, RIPK1) and the MLKL substrate. Losses of RIPK3 or MLKL, as well as deficiency in apoptosis, could allow tumor cells to escape the immunomediated cells death (ICD). Methods: We performed SNP Arrays (Cytoscan HD and SNP 6.0, Affymetrix) on a cohort of 300 non-M3 AML patients at diagnosis and we analyzed the Overall Survival (OS) of our patients with deficiency on necroptosis pathways. Survival was analyzed with Kaplan-Mayer method and Log-Rank test. We further analyze the relevance of different prognostic factors by the use of COX-Hazard Ratio statistical analysis. Results: We find that 18 patients presented a loss of RIPK1 or MLKL (nobody presented losses in RIPK3/RIPK2) and 13/18 patients were older than 65 years old. The Overall Survival (OS) of patients with alterations in these genes is significantly lower than control group, with a median OS of 3 vs 6 month respectively (p

Published
2017

40. A Fuzzy Logic-Based Retrofit System for Enabling Smart Energy-Efficient Electric Cookers

Author

Hani Hagras, Alessandro Ghelli, and Ghadah Aldabbagh

Subjects
Water heating, business.industry, Computer science, Applied Mathematics, Cooker, Fuzzy logic, Automotive engineering, Computational Theory and Mathematics, Safe operation, Artificial Intelligence, Control and Systems Engineering, Electricity, business, Efficient energy use
Abstract

In recent years, our homes have been equipped with smarter and more energy-efficient electric appliances, such as smart fridges, washing machines, TVs, etc. However, it seems that cookers seem to have been left aside during this trend although, for example, in U.K., electric cookers consume up to 20% of the evening peak electricity consumption. In addition, over half of the accidental house fires are due to cooking and cooking appliances. One of the reasons for the lack of smart energy-efficient electric cookers is the complexity of performing energy-efficient control for the various cooking techniques. This paper presents a fuzzy logic-based system, which can be cheaply retrofitted in existing electric cookers to convert them to semiautonomous, energy efficient, and safe smart electric cookers. The proposed system can control the cooker heating plate to allow the semiautonomous safe operation of the most common cooking techniques including boiling, stir/shallow-frying, deep-frying, and warming. In addition, the developed system can identify when human intervention is necessary and when dangerous situations happen or are imminent. We will present several real-world experiments, which were performed in the University of Essex intelligent apartment (iSpace) with various users where the proposed system operated a cooker semiautonomously in various cooking modes, and it was shown that when compared with the human manual operation, the proposed system realized an average energy saving of 21.42%, 34.43%, and 20.29% for the boiling, stir/shallow-frying, and deep-frying cooking techniques, respectively. In addition, the realized smart cooker has shown unique safety features not present in the existing commercial cookers.

Published
2015

41. G02 Decision-making in predictive testing in huntington’s disease

Author

Benedetta Nacmias, S. Latorraca, Sandro Sorbi, Camilla Ferrari, E Ghelli, Silvia Piacentini, Francesco Rotella, Silvia Bagnoli, Eleonora Volpi, Eleonora Mascherini, Federica Terenzi, and Claudio Bartolozzi

Subjects
Protocol (science), medicine.diagnostic_test, business.industry, Neurological examination, Disease, medicine.disease, Test (assessment), Psychological evaluation, Huntington's disease, medicine, Family history, business, Predictive testing, Clinical psychology
Abstract

Objective The protocol for genetic test in at-risk individuals for Huntington Disease provides a neurological examination and a psychiatric evaluation before to begin the psychological counseling, that provides to engage the client in at least two or more psychological session aimed to support the decision-making process. The present study investigated the at-risk subjects’ decision to engage psychological counselling and to carry out genetic test. Materials The collected data were obtained through the recruitment of people with HD and their families within the European Huntington’s Disease Network (EHDN). Using the EHDN Registry, data on clinical signs and symptoms of HD are collected together with the family history of the disease and the data obtained by neurocognitive tests and self-report questionnaires. Methods One hundred and three individuals at risk for Huntington Disease have been included in the study, obtained from clinical data collected from 2007 and 2017 at the HD Center in Careggi Teaching Hospital. Data were manually retrieved from clinical records and included in a database for analyses. Results Forty-four (42.7%) subjects, out of 103 at-risk individuals, decided to start the protocol and engaged on psychological counselling about decision making for genetic test. Thirty-one (70.4%) subjects, out of 44 subjects who undertook the protocol, decided to carry out genetic test,while thirteen (30.6%) subjects decided to temporarily stop the psychological counselling. Within our sample, 18 females (58%) have undergone genetic test, among them 13 (72,2%) were in reproductive period (average age of 29,4 years). Discussion The study examined changes in decision-making for and against the predictive genetic test for Huntington’s disease during psychological counselling. Our data highlight that a high proportion of subjects changed the initial decision of having the genetic test after psychological counselling, preferring uncertainty to the chance of a negative result.

Published
2018

42. 1676b The management of psychosocial risks 9 years after the implementation of the european framework agreement on work-related stress in italy: a monitoring study

Author

C Di Tecco, Benedetta Persechino, Monica Ghelli, Matteo Ronchetti, and Sergio Iavicoli

Subjects
Documentation, Process management, Work (electrical), Psychological intervention, Overtime, Workers' compensation, Business, Psychosocial, Occupational safety and health, Framework agreement
Abstract

In 2008, Italy implemented the 2004 European Framework Agreement on work-related stress into the national legal framework on health and safety at work (L.D. 81/08). Then, the Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, currently part of the Italian Workers Compensation Authority (INAIL), offered to companies a methodology for the assessment and management of risks associated with work-related stress as a participative proposal based on an evidence-based approach and validated tools. The INAILs methodology comes from the adaptation of the HSE’s Management Standards approach and integrates findings of the most prominent national existing experiences and the legal requirements as well. INAIL offered also a web platform, consisting of an operational web interface where companies can have free access to the online tools and find useful documentation to support companies with a web interface as well as to create a structured repository where assessment data from companies are constantly collected. The INAIL methodology resulted in being the most used methodology by Italian companies and data collected through the web platform were useful in the view of optimising and standardising the tools over time. Recent findings showed the state of art of Italian enterprises in managing psychosocial risks resulting from a project financed by the Ministry of Health, involving INAIL as principal investigators, regional prevention units and two universities. This project aimed to offer a monitoring and intervention plan for the optimisation of the assessment and management of psychosocial risks at work in the view of contributing to the evaluation of the policy interventions’ effectiveness. A further study showed the growing level of awareness and the impact of policies on psychosocial risks and work-related stress in Italy using EU-OSHA’s European survey of enterprises on new and emerging risks (ESENER) data. Italian companies have shown a radical change in the management of psychosocial risks overtime and Italy has gone from being a country not prioritising these risks enough to one of the most active European countries in this area.

Published
2018

43. 1338 Addressing psychosocial risk factor in the healthcare sector: the update of inail methodology with new assessment tools

Author

C Di Tecco, C Consiglio, C Balducci, Matteo Ronchetti, Sergio Iavicoli, Monica Ghelli, and B Persechino

Subjects
business.industry, Applied psychology, Health care, Job satisfaction, Context (language use), Risk factor (computing), Psychology, Emotional exhaustion, business, Psychosocial, Focus group, Checklist
Abstract

Introduction Psychosocial Risk Factors was been a long-standing concerns of the healthcare sector. Several studies have shown that healthcare professionals are at an increased risk of work-related stress compared with other professionals. In Italy, according to the INSULA Survey findings, the healthcare sector was ranked first in terms of exposure to work-related stress risk. Therefore, specific approaches are needed to implement the assessment and management of psychosocial risk factors in this area. Methods Starting from an existing methodology for the assessment and management of work related stress risk, that include a checklist (consisting of organisational indicators and work content and context factor) and a validated questionnaire (for the analysis of employees’ perceptions related to seven organisational risk factors), we have identified specific topics for the health sector. Specifically, a detailed literature review has been carried out, followed by two focus groups with OSH professionals and experts of health sector, in order to identify what specific topics should be included. Subsequently, new tools were tested, involving 4 hospitals (more than 3000 workers). Results Regarding the checklist, we have added: seven organisational indicators (eg. patients aggressions, precarious workers, ward mortality ratio) and seven work content and context factors (eg. shift work, organisational changes, procedures for managing conflicts). Among the additional scales of the questionnaire, those that reported better correlations with the pre-existing ones are: work-family conflict, emotional burden, poor team integration, and defensive attitude. Additionally, four outcome variables were added: work satisfaction, turnover Intentions, emotional exhaustion and relational burnout. Discussion Within the framework of a research project funded by the Italian Ministry of Health, the Inail methodology has been integrated with new tools in order to provide a customised path for the healthcare sector. This proposal will be made available through an online platform for data collection and analysis.

Published
2018

44. Greenness effect on oxidative stress and respiratory flows in children

Author

Bono R, Bellisario, Squillacioti G, Ghelli F, Piccioni P, and Borgogno Mondino E

Subjects
Global and Planetary Change, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Medicine, Physiology, Respiratory system, business, medicine.disease_cause, Pollution, Oxidative stress
Published
2019

45. PS931 ADULT TRIPLE NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA FUSION DETECTION: CHALLENGING AIM FOR PH- ALTERNATIVE THERAPIES

Author

Giulia Ferrari, Alessandra Santoro, Michela Tebaldi, Giovanni Martinelli, Daniel Remondini, A. Ghelli Luserna Di Rora, Valentina Robustelli, Giovanni Marconi, Nicoletta Testoni, Antonella Padella, Carmen Baldazzi, Samanta Salvi, Anna Maria Ferrari, Daniele Calistri, Stefania Paolini, Giovanni Pasquini, Enrica Imbrogno, Eugenio Fonzi, Maria Teresa Bochicchio, Jesús M. Hernández-Rivas, Cristina Papayannidis, Gastone Castellani, and Silvia Vitali

Subjects
business.industry, Lymphoblastic Leukemia, Cancer research, Medicine, Hematology, business, Triple negative
Published
2019

46. An Ambient Intelligent and Energy Efficient Food Preparation System Using Linear General Type-2 Fuzzy Logic Based Computing with Words Framework [Application Notes]

Author

Ghadah Aldabbagh, Daniyal M. Alghazzawi, Hani Hagras, Aysenur Bilgin, and Alessandro Ghelli

Subjects
Ambient intelligence, Computer science, business.industry, Fuzzy set, Interval (mathematics), Energy consumption, Machine learning, computer.software_genre, Fuzzy logic, Theoretical Computer Science, Artificial Intelligence, Human–computer interaction, Home automation, Artificial intelligence, business, computer, Energy (signal processing), Efficient energy use
Abstract

Ambient Intelligence (AmI) is a multidisciplinary paradigm, which positively alters the relationship between humans and technology. Concerning home environments, the functions of AmI vision include home automation, communication, entertainment, working and learning. In the area of communication, AmI still needs better mechanisms for human-computer communication. A natural human-computer interaction necessitates having systems capable of modelling words and computing with them. For this purpose, the paradigm of Computing With Words (CWWs) can be employed to mimic human-like communication in Ambient Intelligent Environments (AIEs). This paper demonstrates the extendibility of Linear General Type-2 (LGT2) Fuzzy Logic based CWWs Framework to create an advanced real-world application, which integrates a semi-autonomous, safe and energy efficient electric hob. The motivation of this work is twofold: 1) there is a need to develop transparent human-computer communication rather than embedding obtrusive tablets and computing equipment throughout our surroundings, and 2) one of the most hazardous and energy consuming household devices, the electric hob, does not have competent levels of intelligence and energy efficiency. The proposed Ambient Intelligent Food Preparation System (AIFPS) can increase user comfort, facilitate food preparation, minimize energy consumption and be a useful tool for the elderly and people with major disabilities including vision impairment. The results of real-world experiments with various lay users in the intelligent flat (iSpace) show the success of AIFPS in providing up to 55.43% improved natural interaction (compared to Interval Type-2 based CWWs Framework) while achieving semi-autonomous, safe and energy efficient cooking that can save energy between 11.5% and 35.2%.

Published
2015

47. Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts

Author

Giovanni Rombolà, Benedetta Nacmias, Riccardo Saccardi, Letizia Lombardini, Anna Laura Putignano, Berardino Porfirio, Silvia Bagnoli, Pasquale Gallina, Gabriella B. Vannelli, E Ghelli, Benedetta Mazzanti, Nicola Di Lorenzo, Sandra Bucciantini, and Marco Paganini

Subjects
Male, Pathology, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Biomedical Engineering, lcsh:Medicine, Disease, Fetus, Huntington's disease, HLA Antigens, Isoantibodies, Humans, Medicine, Hla antibodies, Transplantation, biology, business.industry, lcsh:R, Cell Biology, Allografts, medicine.disease, Corpus Striatum, Huntington Disease, Human fetal, Immunology, biology.protein, Female, Antibody, business, Allotransplantation
Abstract

Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0–49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

Published
2015

48. Clinical manifestations of intermediate allele carriers in Huntington disease

Author

Cubo E., Ramos-Arroyo M. A., Martinez-Horta S., Martinez-Descalls A., Calvo S., Gil-Polo CAnne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael M Bonelli, Jean-Marc Burgunder, Stephen B Dunnett, Joaquim J Ferreira, Olivia J Handley, Arvid Heiberg, Torsten Illmann, G Bernhard Landwehrmeyer, Jamie Levey, Maria Ramos-Arroyo, Jørgen E Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A C Roos, Ana Rojo Sebastián, Sarah J Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Adrien Come, Leonor Correia Guedes, Ana Maria Finisterra, Monica Bascuñana Garde, Reineke Bos, Sabrina Betz, Jenny Callaghan, Selene Capodarca, Sébastien Charpentier, Wildson Vieira da Silva, Martina Di Renzo, Daniel Ecker, Ruth Fullam, Camille Genoves, Mette Gilling, Carina Hvalstedt, Christine Held, Andrea Horta-Barba, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saul Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Helene Padieu, Laurent Paterski, Nadia Peppa, Beate Rindal, Dawn Rogers, Niini Røren, Pavla Šašinková, Yuri Seliverstov, Catherine Taylor, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Marleen R van Walsem, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Elizaveta Yudina, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Cécile Minet, Pascale Ribaï, Dominique Van Paemel, Lena Hjermind, Oda Jacobsen, Suzanne Lindquist, Jørgen Nielsen, Lisbeth Regeur, Jette Stockholm, Ida Unmack Larsen, Christina Vangsted-Hansen, Tua Vinther-Jensen, Pia Eklund, Heli Hiivola, Hannele Hypponen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Julie Prouzet, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Anne-Catherine Bachoud-Lévi, Farideh Badei, Lotfi Boudali, Catherine Bourdet, Laurent Cléret, Maryline Couette, Cécile Focseneanu, Laurie Lemoine, Graça Morgado, Mehdi Sebaiti, Claire Thiriez, Laetitia Vervoitte, Katia Youssov, Jean-Philippe Azulay, Christelle Chabot, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Christine Garreau, Aicha Ghenam, Hélène Grosjean, Laura Mundler, Marielle Nowak, Roland Raseta, Maïté Bertrand, Fabienne Calvas, Samia Cheriet, Laurent Marquine, Michèle Pierre, Jérémie Pariente, Sandrine Rolland, Alice Seris, Valérie Vaquie, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J Werner, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Carsten Saft, Kai Boelmans, Christos Ganos, Ines Goerendt, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Michael Orth, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Flverly Francis, Sabine Gayde-Stephan, Heike Gorzolla, Bianca Kramer, Rebecca Minschke, Christoph Schrader, Pawel Tacik, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Nicole Göpfert, Eva Hölzner, Herwig Lange, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Nathalia Weber, Michael Bachmeier, Matthias Dose, Nina Hofstetter, Ralf Marquard, Alzbeta Mühlbäck, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süssmuth, Sonja Trautmann, Patrick Weydt, Stephan Klebe, Thomas Musacchio, Christine Leypold, Kerstin Nöth, Claudia Cormio, Marina de Tommaso, Anna Rita Dellomonaco, Olimpia Difruscolo, Giovanni Franco, Vittorio Sciruicchio, Claudia Serpino, Michela Figorilli, Francesco Marrosu, Antonella Muroni, Valeria Piras, Melisa Vacca, Caterina Bartoli, Elisabetta Bertini, Fernanda Fortunato, Elena Ghelli, Andrea Ginestroni, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giuseppe De Michele, Luigi Di Maio, Carlo Rinaldi, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Pierpaolo Sorrentino, Elena Salvatore, Tecla Tucci, Milena Cannella, Valentina Codella, Francesca De Gregorio, Annunziata De Nicola, Francesca Elifani, Tiziana Martino, Francesca Lovo, Irene Mazzante, Martina Petrollini, Maria Simonelli, Ferdinando Squitieri, Maurizio Vezza, Barbara D'Alessio, Chiara Esposito, Giulia Coarelli, Michela Ferraldeschi, Marina Frontali, Gioia Jacopini, Giovanni Ristori, Silvia Romano, Monique S E van Hout, Jeroen P P van Vugt, A Marit de Weert, Marloes Verhoeven, Simon J A van den Bogaard, Eve M Dumas, Ellen P 't Hart, Milou Jacobs, Anne Kampstra, Anne Schoonderbeek, Nils Olav Aanonsen, Olaf Aaserud, Liv Barnett, Kathrine Bjørgo, Nancy Borgerød, Elisabeth Dramstad, Madeleine Fannemel, Jan Frich, Helen Gundersen, Per Gørvell, Kathrine Haggag, Cecilie Haggag Johannessen, Lars Retterstøl, Oddveig Rosby, Jutta Rummel, Alma Sikiric, Olga Solberg, Marleen van Walsem, Ragnhild Wehus, Artur Dziadkiewicz, Agnieszka Konkel, Ewa Narożańska, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Michał Arkuszewski, Magdalena Błaszczyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasińska-Myga, Aleksandra Kaczmarczyk, Gabriela Kłodowska-Duda, Grzegorz Opala, Monika Rudzińska, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Boćwińska, Kamila Bojakowska-Jaremek, Małgorzata Dec, Natalia Grabska, Malgorzata Krawczyk, Ewelina Kubowicz, Michalina Malec-Litwinowicz, Agata Stenwak, Andrzej Szczudlik, Elżbieta Szczygieł, Magdalena Wójcik, Anna Wasielewska, Jacek Anioła Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempołowicz, Bartłomiej Wiśniewski, Anna Gogol, Piotr Janik, Zygmunt Jamrozik, Anna Kaminska, Hubert Kwiecinski, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stępniak, Anna Sułek, Elzbieta Zdzienicka, Karolina Ziora-Jakutowicz, Cristina Januário, Filipa Júlio, Ana Salgueiro, Miguel Coelho, Tiago Mendes, Mário Miguel Rosa, Anabela Valadas, Cristina Semedo, Ana Calado, Joana Morgado, Margarida Dias, Manuel Almeida, Carmen Durán Herrera, Patrocinio Garcia Moreno, Jordi Bas, Núria Busquets, Matilde Calopa, Serge Jaumà Classen, Nadia Rodríguez Dedichá, Miquel Aguilar Barbera, Sonia Arribas Pardo, Dolors Badenes Guia, Noemi Calzado, Laura Casas Hernanz, Juan Pablo Tartari Díaz-Zorita, Judit López Catena, Pilar Quiléz Ferrer, Gemma Tome Carruesco, Misericordia Floriach Robert, Cèlia Mareca Viladrich, Elvira Roca, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Antonia Campolongo, Ramon Fernandez de Bobadilla, Jaime Kulisevsky Bojarsky, Javier Pagonabarraga, Jesus Perez Perez, Carolina Villa, Maria Angeles Acera Gil, Koldo Berganzo Corrales, Juan Carlos Gomez Esteban, Amaia González, Beatriz Tijero Merino, Esther Cubo, Natividad Mariscal, Sandra Gutierrez Romero, José Matías Arbelo, Rocío Malo de Molina, Idaira Martín, Juan Manuel Periañez, Beatriz Udaeta, Fernando Alonso-Frech, Belén Frades, Marina Ávila Villanueva, Maria Ascension Zea Sevilla, Fernando Alonso Frech, María Del Mar Fenollar, Rocío García-Ramos García, Clara Villanueva, Mónica Bascuñana, Marta Fatás Ventura, Juan García Caldentey, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Verónica Mañanes Barral, Cici Feliz Feliz, Pedro José García Ruíz, Ana García, Rosa Guerrero López, Antonio Herranz Bárcenas, Asunción Martínez-Descals, Angel Martínez Pueyo, Veronica Puertas Martin, Noelia Rodríguez Martínez, María José Sainz Artiga, Vicenta Sánchez, Javier Del Val Fernandez, Carmen Antúnez Almagro, Salvadora Manzanares, Juan Marín Muñoz, María Martirio Antequera Torres, Fuensanta Noguera Perea, Laura Vivancos Moreau, Sonia González, Luis Menéndez Guisasola, Carlos Salvador, René Ribacoba, Pablo Sánchez Lozano, Marta Para Prieto, Aránzazu Gorospe, Inés Legarda Ramirez, Penelope Navas Arques, Monica Rodriguez Lopera, Barbara Vives Pastor, Itziar Gaston, Maria Antonia Ramos-Arroyo, Maria Dolores Martinez-Jaurrieta, José Manuel García Moreno, Carolina Mendez Lucena, José Chacón Peña, Fátima Damas Hermoso, Eva Pacheco Cortegana, Luis Redondo, Cristina Melgar Fernandez, Maite Paredes Mata, Maria Dolores Romero Lemos, Maria Bosca, Juan Andres Burguera, Francisco Castera Brugada Carmen Peiró Vilaplana, Elena Bellosta Diago, Javier López Del Val, Laura Martinez Martinez, Elena López, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Liselotte Neleborn-Lingefjärd, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Lorna Downie, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughn, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Monica Busse, Cynthia Butcher, Stephen Dunnett, Catherine Clenaghan, Sarah Hunt, Lesley Jones, Una Jones, Hanan Khalil, Michael Owen, Kathleen Price, Anne Rosser, Peter Brockie, Jillian Foster, Nicola Johns, Sue McKenzie, Jean Rothery, Gareth Thomas, Shona Yates, Alyson Andrew, Julie Frost, Rupert Noad, Jeremy Cosgrove, Deena Gallantree, Stephanie Hamer, Emma Hobson, Stuart Jamieson, Alison Kraus, Mandy Longthorpe, Ivana Markova, Hannah Musgrave, Caroline Peacy, Ashok Raman, Liz Rowett, Jean Toscano, Sue Wild, Carole Clayton, Pam Yardumian, Heather Dipple, Dawn Freire- Patino, Caroline Hallam, Julia Middleton, Uruj Anjum, Jan Coebergh, Charlotte Eddy, Nayana Lahiri, Meriel McEntagart, Michael Patton, Maria Peterson, Sarah Rose, Thomasin Andrews, Stefanie Brown, Stefania Bruno, Elvina Chu, Karen Doherty, Charlotte Golding, Salman Haider, Davina Hensman, Monica Lewis, Marianne Novak, Aakta Patel, Joy Read, Nicola Robertson, Elisabeth Rosser, Sarah Tabrizi, Rachel Taylor, Thomas Warner, Edward Wild, Natalie Arran, Judith Bek, David Craufurd, Marianne Hare, Liz Howard, Susan Huson, Liz Johnson, Mary Jones, Ashok Krishnamoorthy, Helen Murphy, Emma Oughton, Lucy Partington-Jones, Andrea Sollom, Julie Snowden, Cheryl Stopford, Jennifer Thompson, Iris Trender-Gerhard, Nichola Verstraelen, Leann Westmoreland, Ginette Cass, Lynn Davidson, Jill Davison, Neil Fullerton, Katrina Holmes, Suresh Komati, Sharon McDonnell, Zeid Mohammed, Karen Morgan, Lois Savage, Baldev Singh, Josh Wood, Andrea H Nemeth, Gill Siuda, Ruth Valentine, Kathryn Dixon, Richard Armstrong, David Harrison, Max Hughes, Sandra Large, John O Donovan, Amy Palmer, Andrew Parkinson, Beverley Soltysiak, Leanne Timings, Josh Williams, Oliver Bandmann, Alyson Bradbury, Helen Fairtlough, Kay Fillingham, Isabella Foustanos, Paul Gill, Mbombe Kazoka, Kirsty O'Donovan, Louise Nevitt, Oliver Quarrell, Cat Taylor, Katherine Tidswell, Lesley Gowers, Kingsley Powell, Pamela Bethwaite, Rachel Edwards, Kathleen Fuller, Michelle Phillips, Univ Angers, Okina, E., Cubo, M. A., Ramos-Arroyo, S., Martinez-Horta, A., Martinez-Descall, S., Calvo, CAnne-Catherine Bachoud-Lévi, Gil-Polo, Rita Bentivoglio, Anna, Biunno, Ida, M Bonelli, Raphael, Burgunder, Jean-Marc, B Dunnett, Stephen, J Ferreira, Joaquim, J Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Bernhard Landwehrmeyer, G, Levey, Jamie, Ramos-Arroyo, Maria, E Nielsen, Jørgen, Pro Koivisto, Susana, Päivärinta, Markku, C Roos, Raymund A, Rojo Sebastián, Ana, J Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Come, Adrien, Correia Guedes, Leonor, Maria Finisterra, Ana, Bascuñana Garde, Monica, Bos, Reineke, Betz, Sabrina, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Hvalstedt, Carina, Held, Christine, Horta-Barba, Andrea, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Martínez Descals, Asunción, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren, Niini, Šašinková, Pavla, Seliverstov, Yuri, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Trigo Cubillo, Patricia, R van Walsem, Marleen, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, Hjermind, Lena, Jacobsen, Oda, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Stockholm, Jette, Unmack Larsen, Ida, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Eklund, Pia, Hiivola, Heli, Hypponen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau Marie Bost, Dominique, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duché, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Bachoud-Lévi, Anne-Catherine, Badei, Farideh, Boudali, Lotfi, Bourdet, Catherine, Cléret, Laurent, Couette, Maryline, Focseneanu, Cécile, Lemoine, Laurie, Morgado, Graça, Sebaiti, Mehdi, Thiriez, Claire, Vervoitte, Laetitia, Youssov, Katia, Azulay, Jean-Philippe, Chabot, Christelle, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Garreau, Christine, Ghenam, Aicha, Grosjean, Hélène, Mundler, Laura, Nowak, Marielle, Raseta, Roland, Bertrand, Maïté, Calvas, Fabienne, Cheriet, Samia, Marquine, Laurent, Pierre, Michèle, Pariente, Jérémie, Rolland, Sandrine, Seris, Alice, Vaquie, Valérie, Michael Kosinski, Christoph, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johanne, Schlangen, Christiane, J Werner, Corneliu, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Saft, Carsten, Boelmans, Kai, Ganos, Christo, Goerendt, Ine, Heinicke, Walburgi, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Stubbe, Lar, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Lange, Herwig, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthia, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Klebe, Stephan, Musacchio, Thoma, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, de Tommaso, Marina, Rita Dellomonaco, Anna, Difruscolo, Olimpia, Franco, Giovanni, Sciruicchio, Vittorio, Serpino, Claudia, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bartoli, Caterina, Bertini, Elisabetta, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Maria Romoli, Anna, Sorbi, Sandro, DE MICHELE, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, CINZIA VALERIA, Sorrentino, Pierpaolo, Salvatore, Elena, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Martino, Tiziana, Lovo, Francesca, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Squitieri, Ferdinando, Vezza, Maurizio, D'Alessio, Barbara, Esposito, Chiara, Coarelli, Giulia, Ferraldeschi, Michela, Frontali, Marina, Jacopini, Gioia, Ristori, Giovanni, Romano, Silvia, E van Hout, Monique S, P van Vugt, Jeroen P, Marit de Weert, A, Verhoeven, Marloe, A van den Bogaard, Simon J, M Dumas, Eve, P 't Hart, Ellen, Jacobs, Milou, Kampstra, Anne, Schoonderbeek, Anne, Olav Aanonsen, Nil, Aaserud, Olaf, Barnett, Liv, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan, Gundersen, Helen, Gørvell, Per, Haggag, Kathrine, Haggag Johannessen, Cecilie, Retterstøl, Lar, Rosby, Oddveig, Rummel, Jutta, Sikiric, Alma, Solberg, Olga, van Walsem, Marleen, Wehus, Ragnhild, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska-Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anioła Anna Bryl, Jacek, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol, Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Salgueiro, Ana, Coelho, Miguel, Mendes, Tiago, Miguel Rosa, Mário, Valadas, Anabela, Semedo, Cristina, Calado, Ana, Morgado, Joana, Dias, Margarida, Almeida, Manuel, Durán Herrera, Carmen, Garcia Moreno, Patrocinio, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Jaumà Classen, Serge, Rodríguez Dedichá, Nadia, Aguilar Barbera, Miquel, Arribas Pardo, Sonia, Badenes Guia, Dolor, Calzado, Noemi, Casas Hernanz, Laura, Pablo Tartari Díaz-Zorita, Juan, López Catena, Judit, Quiléz Ferrer, Pilar, Tome Carruesco, Gemma, Floriach Robert, Misericordia, Mareca Viladrich, Cèlia, Roca, Elvira, Miguel Ruiz Idiago, Jesú, Villa Riballo, Antonio, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Kulisevsky Bojarsky, Jaime, Pagonabarraga, Javier, Perez Perez, Jesu, Villa, Carolina, Angeles Acera Gil, Maria, Berganzo Corrales, Koldo, Carlos Gomez Esteban, Juan, González, Amaia, Tijero Merino, Beatriz, Cubo, Esther, Mariscal, Natividad, Gutierrez Romero, Sandra, Matías Arbelo, José, Malo de Molina, Rocío, Martín, Idaira, Manuel Periañez, Juan, Udaeta, Beatriz, Alonso-Frech, Fernando, Frades, Belén, Ávila Villanueva, Marina, Ascension Zea Sevilla, Maria, Alonso Frech, Fernando, Del Mar Fenollar, María, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Fatás Ventura, Marta, García Caldentey, Juan, García Ribas, Guillermo, García de Yébenes, Justo, Luis López-Sendón Moreno, José, Mañanes Barral, Verónica, Feliz Feliz, Cici, José García Ruíz, Pedro, García, Ana, Guerrero López, Rosa, Herranz Bárcenas, Antonio, Martínez-Descals, Asunción, Martínez Pueyo, Angel, Puertas Martin, Veronica, Rodríguez Martínez, Noelia, José Sainz Artiga, María, Sánchez, Vicenta, Del Val Fernandez, Javier, Antúnez Almagro, Carmen, Manzanares, Salvadora, Marín Muñoz, Juan, Martirio Antequera Torres, María, Noguera Perea, Fuensanta, Vivancos Moreau, Laura, González, Sonia, Menéndez Guisasola, Lui, Salvador, Carlo, Ribacoba, René, Sánchez Lozano, Pablo, Para Prieto, Marta, Gorospe, Aránzazu, Legarda Ramirez, Iné, Navas Arques, Penelope, Rodriguez Lopera, Monica, Vives Pastor, Barbara, Gaston, Itziar, Antonia Ramos-Arroyo, Maria, Dolores Martinez-Jaurrieta, Maria, Manuel García Moreno, José, Mendez Lucena, Carolina, Chacón Peña, José, Damas Hermoso, Fátima, Pacheco Cortegana, Eva, Redondo, Lui, Melgar Fernandez, Cristina, Paredes Mata, Maite, Dolores Romero Lemos, Maria, Bosca, Maria, Andres Burguera, Juan, Castera Brugada Carmen Peiró Vilaplana, Francisco, Bellosta Diago, Elena, López Del Val, Javier, Martinez Martinez, Laura, López, Elena, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Weber Zaugg, Sabine, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, A Simpson, Sheila, Summers, Fiona, Ure, Alexandra, Vaughn, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hamer, Stephanie, Hobson, Emma, Jamieson, Stuart, Kraus, Alison, Longthorpe, Mandy, Markova, Ivana, Musgrave, Hannah, Peacy, Caroline, Raman, Ashok, Rowett, Liz, Toscano, Jean, Wild, Sue, Clayton, Carole, Yardumian, Pam, Dipple, Heather, Freire- Patino, Dawn, Hallam, Caroline, Middleton, Julia, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Brown, Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Golding, Charlotte, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Read, Joy, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Loi, Singh, Baldev, Wood, Josh, H Nemeth, Andrea, Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, O Donovan, John, Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Quarrell, Oliver, Taylor, Cat, Tidswell, Katherine, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Cubo, E., Ramos-Arroyo, M. A., Martinez-Horta, S., Martinez-Descalls, A., Russo, C. V., Calvo, S., Gil-Polo, C., Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Ramos-Arroyo, María A., Martínez-Descalls, Asunción, Calvo, Sara, and Gil-Polo, Cecilia

Subjects
0301 basic medicine, Registrie, Adult, Male, medicine.medical_specialty, Aging, Heterozygote, Genetic counseling, Motor Disorders, Disease, Severity of Illness Index, 03 medical and health sciences, Cognition Disorder, 0302 clinical medicine, Trinucleotide Repeats, Internal medicine, medicine, Humans, Registries, Allele, Motor Disorder, Alleles, Huntingtin Protein, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Medicine (all), Trinucleotide Repeat, Cognition, Genetic Status, Middle Aged, Phenotype, Europe, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Huntington Disease, Case-Control Studies, Cohort, medicine (all), neurology (clinical), controlled clinical trial (topic), Quality of Life, Female, Neurology (clinical), business, Case-Control Studie, Cognition Disorders, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Human
Abstract

International audience; OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with RESULTS: Of 12,190 participants, 657 (5.38%) with CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

Published
2016

49. Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia

Author

Andrea Ghelli Luserna di Rorà, Maria Chiara Abbenante, Sarah Parisi, Enrico Derenzini, Chiara Sartor, Cristina Papayannidis, Stefania Paolini, Viviana Guadagnuolo, Anna Maria Ferrari, Enrica Imbrogno, Valentina Robustelli, Ilaria Iacobucci, Giovanni Martinelli, GHELLI LUSERNA DI RORÀ, Andrea, Iacobucci, Ilaria, Imbrogno, Enrica, Papayannidis, Cristina, Derenzini, Enrico, Ferrari, Anna, Guadagnuolo, Viviana, Robustelli, Valentina, Parisi, Sarah, Sartor, Chiara, Abbenante, Maria Chiara, Paolini, Stefania, and Martinelli, Giovanni

Subjects
0301 basic medicine, Dasatinib, Apoptosis, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, DNA damage response, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Clofarabine, Hematology, Adenine Nucleotides, Cell Cycle, Drug Synergism, Cell cycle, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Pyrazines, Imatinib Mesylate, medicine.drug, Research Paper, medicine.medical_specialty, Cell Survival, CHK1, Antineoplastic Agents, acute lymphoblastic leukemia, 03 medical and health sciences, Internal medicine, Cell Line, Tumor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, chemo-sensitizer agent, Humans, CHEK1, Propidium iodide, Protein Kinase Inhibitors, business.industry, Imatinib, Checkpoint Kinase 2, 030104 developmental biology, chemistry, Immunology, Checkpoint Kinase 1, Cancer research, Adult Acute Lymphoblastic Leukemia, Pyrazoles, Arabinonucleosides, business
Abstract

// Andrea Ghelli Luserna Di Rora 1 , Ilaria Iacobucci 1, * , Enrica Imbrogno 1 , Cristina Papayannidis 1 , Enrico Derenzini 1 , Anna Ferrari 1 , Viviana Guadagnuolo 1 , Valentina Robustelli 1 , Sarah Parisi 1 , Chiara Sartor 1 , Maria Chiara Abbenante 1 , Stefania Paolini 1 , Giovanni Martinelli 1, * 1 Institute of Hematology “L. e A. Seragnoli”, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy * Co-corresponding authors Correspondence to: Ilaria Iacobucci, email: ilaria.iacobucci2@unibo.it Giovanni Martinelli, email: giovanni.martinelli2@unibo.it Keywords: CHK1, cell cycle, acute lymphoblastic leukemia, DNA damage response, chemo-sensitizer agent Received: February 12, 2016 Accepted: June 30, 2016 Published: July 11, 2016 ABSTRACT During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of γH2A.X protein expression and by the activation of different apoptotic markers (Parp-1 and pro-Caspase3 cleavage). Furthermore, the inhibition of Chk1 changed the cell cycle profile. In order to evaluate the chemo-sensitizer activity of the compound, different cell lines were treated for 24 and 48 hours with prexasertib in combination with other drugs (imatinib, dasatinib and clofarabine). The results from cell line models were strengthened in primary leukemic blasts isolated from peripheral blood of adult acute lymphoblastic leukemia patients. In this study we highlighted the mechanism of action and the effectiveness of prexasertib as single agent or in combination with other conventional drugs like imatinib, dasatinib and clofarabine in the treatment of B-/T-ALL.

Published
2016

50. Survival and outcome data observed in 98 patients affected by acute myeloid leukemia undergoing chemotherapy consolidation courses treatment followed by autologous bone marrow transplantation (auto-BMT)

Author

Giovanni Marconi, Andrea Ghelli Luserna di Rorà, Federico Mosna, Cristina Tecchio, Emanuela Ottaviani, Viviana Guadagnuolo, Giuseppe Visani, Marco Manfrini, Michele Gottardi, Elena Tenti, Giorgia Simonetti, Andrea Piccin, Filippo Gherlinzoni, Maria Chiara Fontana, Debora Capelli, Cristina Papayannidis, Francesco Rodeghiero, Piero Galieni, Eugenia Franchini, Giovanni Martinelli, Marconi, Giovanni, Papayannidis, Cristina, Mosna, Federico, Gottardi, Michele, Tenti, Elena, Franchini, Eugenia, GHELLI LUSERNA DI RORÀ, Andrea, Ottaviani, Emanuela, Fontana, MARIA CHIARA, Simonetti, Giorgia, Guadagnuolo, Viviana, Manfrini, Marco, Capelli, Debora, Galieni, Piero, Piccin, Andrea, Visani, Giuseppe, Rodeghiero, Francesco, Tecchio, Cristina, Gherlinzoni, Filippo, and Martinelli, Giovanni

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Consolidation (soil), business.industry, Marrow transplantation, medicine.medical_treatment, chemioterapia, trapianto autologo, Myeloid leukemia, Autologous bone, Surgery, Standard Risk, hemic and lymphatic diseases, Internal medicine, Medicine, Outcome data, business
Abstract

e18520Background: In a specific subset of patients, Auto-BMT may represent a good therapeutic option. It is used worldwide in consolidation of both low risk, and standard risk AML without an availa...

Published
2016

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