El problema del viajante: recorridos hamiltonianos

En el contexto de una convicción que sostenemos desde hace varios años y a partir de distintas investigaciones que hemos realizado con el fin de evaluar la viabilidad de introducir algunos conceptos de grafos en distintos niveles educativos, nos volvemos a plantear cuáles y cuántos de ellos son adecuados para llevar a las aulas de primaria y secundaria. Este trabajo, en particular, se refiere a los grafos hamiltonianos, como el mismo es un problema aún abierto no lo habíamos trabajado específicamente en estos niveles. Este trabajo tiene como objetivo presentar las actividades llevadas a cabo con niños de distintas edades, las que consideramos permiten a los alumnos construir el concepto de recorrido hamiltoniano con el fin de identificar edades mínimas para cada propuesta y a partir de esto es posible dar una cierta graduación de los contenidos en cada uno de los niveles

Effects of different steam injection conditions on cappuccino's nutritional profile

The quality parameters of cappuccinos prepared with pasteurized milk or ultra-high-temperature milk steam-injected at different temperatures by a professional coffee machine have been assessed. In particular, the protein profile, the content of vitamins and lactose, the lipid peroxidation process, and the involvement of milk proteins in the foam formation were evaluated. The nutritional quality of milk seems not affected by the steam injection treatment carried out at a temperature of 60–65 °C, but at higher temperatures a decrement of lactoperoxidase, vitamin B6 and folic acid was observed. The milk used in cappuccino preparation is very important: pasteurized milk can form a more consistent and lasting foam with respect to ultra-high-temperature milk because of the presence of β-lactoglobulin and lactoferrin, both playing an important role in the foam formation and stability. This work would provide additional information to the coffee industry for the preparation of high nutritional and organoleptic quality cappuccinos

Valorizzare il patrimonio culturale attraverso il pubblico dominio. Il Pubblico dominio open festival di Torino come caso di studio

The Urban Library Project on Public Domain is the result of a good practice of interinstitutional cooperation which was ratified by a specific convention between the ‘library systems’ of the University of Turin, the Polytechnic of Turin, the Turin Public Libraries and the Foundation “Teatro Nuovo”. This project aims at promoting and disseminating the concept of public domain to highlight its social, cultural and economic importance. By promoting the knowledge and enrichment of cultural heritage, it is possible to design a ‘public domain supply chain’ which can exploit different cultural and social actions. In its early stage, this project offered people a number of educational and entertaining events which were related to the works of the authors who gradually entered into Public Domain.The public domain #open festival was organized for the first time in Italy in 2016 with the aim of extending the range of action of previous experiences. In 5 days a total amount of almost 50 special events (conferences, meetings, workshops, exhibitions, shows, theatrical readings, etc.) related to art, photography, music, literature, theater, cinema and more were offered. This festival was like a party; a large container where everyone was able to learn the meaning and the different facets of public domain (and the cultures related to openness) by appreciating its ethical and economic value in any field of human knowledge.This contribution wants to be an opportunity to reflect on public domain and open cultures and stimulate interest on them beyond the temporal dimension of a festival.Il Progetto bibliotecario urbano sul pubblico dominio è frutto di una buona pratica di cooperazione interistituzionale tra ‘sistemi bibliotecari’ dell’Università di Torino, del Politecnico di Torino, delle Biblioteche Civiche Torinesi con la Fondazione Teatro Nuovo, ratificata da una convenzione dedicata. Il progetto intende promuovere e diffondere il concetto di pubblico dominio, sottolinearne l’importanza sociale, culturale ed economica, e disegnare una possibile ‘filiera del pubblico dominio’, finalizzata a promuovere la conoscenza e la valorizzazione del patrimonio culturale, declinata in molteplici azioni culturali e sociali; nella sua fase iniziale si è articolato in una serie di eventi divulgativi, formativi e di intrattenimento, legati alle opere degli autori che via via entravano a far parte del Pubblico Dominio.Il Pubblico dominio #open festival, realizzato per la prima volta in Italia nel 2016, è partito da quest’esperienza per ampliarne il raggio d’azione. Sono stati 5 giorni di conferenze, incontri, laboratori, mostre, spettacoli, letture teatrali per un totale di quasi 50 eventi speciali che hanno investito i diversi ambiti dell’arte, della fotografia, della musica, della letteratura, del teatro, del cinema e molto altro! Una festa, un grande contenitore dove tutti hanno potuto apprendere il significato e le diverse sfaccettature del pubblico dominio (e delle culture legate all’open), apprezzarne la valenza etica ed economica in ogni campo della conoscenza umana.Il contributo attuale si propone di essere un’occasione di riflessione, seppur ad una certa distanza temporale dall’evento, per arrivare a progettare una nuova edizione del festival, in forma rinnovata ed ampliata e al tempo stesso ha l’ambizione di stimolare l’interesse sulle tematiche legate al pubblico dominio e alle culture open, oltre la dimensione temporale del festival

Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma

In recent years, BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi), together with immune checkpoint inhibitors (ICIs), have changed the therapeutic strategy of cutaneous melanoma, both in adjuvant and metastatic settings. These inhibitors have significantly improved the clinical outcome for patients with melanoma, including in both BRAF-mutated and BRAF-wild type disease. Some preclinical and clinical studies have revealed that BRAFi and MEKi are able to influence T- and B-cell activation, and to modulate immune system activation within the tumor microenvironment. Dabrafenib and trametinib have been shown to enhance the expression of melanoma antigens on BRAF-mutated cells, and to favor both a cytotoxic and immune response against melanoma cells. Thereby, the present study described a case series of five women treated with BRAFi and MEKi, in both adjuvant and metastatic settings, that experienced potential immune-related adverse events. In particular, these patients exhibited sarcoidosis, mesenteric panniculitis, lymphocytic colitis and neuropathy of phrenic nerve. Considering that T and B cells are responsible for immune-related adverse events, as observed in patients treated with ICIs, the present study suggested a possible role of BRAFi and MEKi as triggers of immune system activation and subsequent immune-related toxicities

The Landscape of ALK-Rearranged Non-Small Cell Lung Cancer: A Comprehensive Review of Clinicopathologic, Genomic Characteristics, and Therapeutic Perspectives

During the last decade, the identification of oncogenic driver mutations and the introduction of tyrosine kinase inhibitors (TKIs) in daily clinical practice have substantially revamped the therapeutic approach of oncogene-addicted, non-small cell lung cancer (NSCLC). Rearrangements in the anaplastic lymphoma kinase (ALK) gene are detected in around 3–5% of all NSCLC patients. Following the promising results of Crizotinib, a first-generation ALK inhibitor (ALK-i), other second-generation and more recently third-generation TKIs have been developed and are currently a landmark in NSCLC treatment, leading to a significant improvement in patients prognosis. As clinical trials have already demonstrated high efficacy of each ALK-i, both in terms of systemic and intracranial disease control, comparative studies between second and third generation ALK-i are still lacking, and primary or secondary ALK-i resistance inevitably limit their efficacy. Resistance to ALK-i can be due to ALK-dependent or ALK-independent mechanisms, including the activation of bypass signaling pathways and histological transformation: these findings may play an important role in the future to select patients’ subsequent therapy. This review aims to provide an overview of underlying molecular alterations of ALK-i resistance and point out promising role of liquid biopsy in predicting tumor response and monitoring resistance mutations. The purpose of this review is also to summarize current approval for ALK-rearranged NSCLC patients, to help clinicians in making decisions on therapeutic sequence, and to deepen the role of clinicopathological and genomic characteristics influencing patients’ prognosis during treatment with ALK-i

Tumor burden as possible biomarker of outcome in advanced NSCLC patients treated with immunotherapy: a single center, retrospective, real-world analysis

none11Aim: The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients. Methods: Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Results: Median age was 70 years and most patients (86.2%) had a good performance status (PS-Eastern Cooperative Oncology Group 4 were negative prognostic factors (P < 0.0001). Conclusions: This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.restrictedEdoardo Lenci; Giulia Marcantognini; Valeria Cognigni; Alessio Lupi; Silvia Rinaldi; Luca Cantini; Ilaria Fiordoliva; Anna Lisa Carloni; Lina Zuccatosta; Stefano Gasparini; Rossana BerardiLenci, Edoardo; Marcantognini, Giulia; Cognigni, Valeria; Lupi, Alessio; Rinaldi, Silvia; Cantini, Luca; Fiordoliva, Ilaria; Lisa Carloni, Anna; Zuccatosta, Lina; Gasparini, Stefano; Berardi, Rossan

Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type

: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment

The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRIm Delta = GRImT0 - GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRIm Delta had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRIm Delta. Conclusion: Our data shown that GRImT1 and GRIm Delta are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting

91 Circulating lipid profile as a prognostic factor in patients with advanced solid tumors treated with immune checkpoint inhibitors

Background Components of lipid profile seem to impact differently on phenotype and activity of immune cells in cancer.1,2 Their prognostic role in solid cancer patients treated with immune checkpoint inhibitors (ICIs) is still matter of debate. Methods We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile [total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL)] of consecutive solid cancer patients treated with ICIs and we investigated their impact on clinical outcomes. Cut-off values showing alteration of plasma lipid profile were ≥200 mg/dl for TC, ≥170 mg/dl for TGs, ≥130 mg/dl for LDL, &lt;40 mg/dl for HDL in males, &lt;45 mg/dl for HDL in females. Results Among 432 patients enrolled, 67% (N=289) were men, 61% (N=266) were diagnosed with advanced non-small cell lung cancer and 86.6% (N=374) of patients were treated with ICIs as monotherapy. Patients’ circulating lipid assessments were described in tables (tables 1–3). At a median follow-up of 46 months, patients with TC≥200 mg/dl showed an improved, although not significant, progression free survival (PFS) (6.61 versus 4.67 months, p=0.4) and longer overall survival (OS) (19.4 versus 10.8 months, p=0.02) compared to those with TC&lt;200 mg/dl. Conversely, patients with TGs≥170 mg/dl showed a shorter PFS (2.8 versus 5.07 months, p=0.006) and OS (5.92 versus 12.99 months, p&lt;0.001) compared to those with TGs&lt;170 mg/dl. Then, we combined TC and TGs in a LIPID-score that identified three subgroups: good risk (GR) (TC≥200 mg/dl and TGs&lt;170 mg/dl), intermediate risk (IR) (TC&lt;200 mg/dl and TGs&lt;170 mg/dl or TC≥200 mg/dl and TGs≥170 mg/dl) and poor risk (PR) (TC&lt;200 mg/dl and TGs≥170 mg/dl). The median PFS of GR, IR and PR groups was 7.76, 4.18 and 2.40 months, respectively (p&lt;0.001). Moreover, median OS of GR, IR and PR was 20.36, 11.18 and 4.14 months, respectively (p&lt;0.001) (figure 1). At multivariate analyses, after adjusting for baseline performance status, histology, treatment line, sex, statin use, number of metastatic sites and body mass index, the impact of LIPID score remained significant for both PFS and OS (table 4). Looking at TC components, HDL and LDL, a significant association was detected only for HDL and OS, with patients characterized by higher HDL levels showing longer OS (15.3 vs 10.1 months, p=0.02). Conclusions LIPID score seems to strongly define subgroups of patients treated with ICIs with different prognosis. Further mechanistic insights are needed to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs

Alarming Drop in Early Stage Colorectal Cancer Diagnoses After COVID-19 Outbreak: A Real-World Analysis from the Italian COVID-DELAY Study

Background: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter Italian study aimed to evaluate whether COVID-19 has impacted access to diagnosis, staging, and treatment for patients newly diagnosed with colorectal cancer (CRC), compared with pre-pandemic time. Methods: All consecutive new CRC patients referred to 8 Italian oncology institutions between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset, radiological and cytohistological diagnosis, treatment start and first radiological evaluation were analyzed and compared with the same months of 2019. Results: A reduction (29%) in newly diagnosed CRC cases was seen when compared with 2019 (360 vs 506). New CRC patients in 2020 were less likely to be diagnosed with early stage (stages I-II-III) CRC (63% vs 78%, P < .01). Gender and sidedness were similar regardless of the year. The percentage of tumors with any mutation among BRAF, NRAS, and KRAS genes were significantly different between the 2 years (61% in 2020 vs 50% in 2019, P = .04). Timing of access to cancer diagnosis, staging, and treatment for patients with CRC has not been negatively affected by the pandemic. Significantly shorter temporal intervals were observed between symptom onset and first oncological appointment (69 vs 79 days, P = .01) and between histological diagnosis and first oncological appointment (34 vs 42 days, P < .01) during 2020 compared with 2019. Fewer CRC cases were discussed in multidisciplinary meetings during 2020 (38% vs 50%, P = .01). Conclusions: Our data highlight a significant drop in CRC diagnosis after COVID-19, especially for early stage disease. The study also reveals a remarkable setback in the multidisciplinary management of patients with CRC. Despite this, Italian oncologists were able to ensure diagnostic-therapeutic pathways proper operation after March 2020