APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

Studies on the Constituents of Amaranthus caudatus Leaves: Isolation and Structure Elucidation of New Triterpenoid Saponins and Ionol-Derived Glycosides

Abstract: The isolation of seven triterpenoid saponins (1−7) is reported, among them three new natural products (1−3), together with three new ionol-derived glycosides (8−10) from the MeOH extract of the leaves of Amaranthus caudatus (Amaranthaceae). All structures were elucidated by spectroscopic methods, including the concerted application of one-dimensional (1H, TOCSY, 13C, and 13C DEPT NMR) and two-dimensional NMR techniques (DQF−COSY, HSQC, HMBC, ROESY). A comparative study of seeds and leaves has been also carried out

Caso studio. Oli essenziali e idrolati nel trattamento di dipinto su tela

L\u2019opera sottoposta a restauro (Il Silenzio, olio su tela 146x163cm) \ue8 stata eseguita nel 1572 da Jacopo Zucchi e fa parte di un ciclo pittorico mitologico costituito da nove tele realizzate dall\u2019artista per decorare una sala di Villa Medici a Roma; successivamente nel 1588 per volere del granduca Ferdinando I de\u2019 Medici le nove tele vennero riadattate da Ludovico Buti per decorare il soffitto della Sala delle Carte Geografiche degli Uffizi a Firenze. Prima e dopo il trattamento sono stati eseguiti prelievi sul retro e sul fronte dell\u2019opera in corrispondenza dell\u2019evidente attacco biodeteriogeno. I prelievi sono stati eseguiti utilizzando tamponi sterili per la ricerca microbiologica e nastro adesivo idoneo per il campionamento su opere d\u2019arte (fungi-tape). I campioni prelevati sono stati immediatamente inviati al laboratorio e analizzati. Lo studio, nei campioni prelevati sul retro del dipinto, ha evidenziato la presenza di Aspergillus versicolor e Penicillium chrysogenum. Per eseguire un trattamento uniforme su tutta la superficie il dipinto \ue8 stato svincolato dal telaio e rimossa la tela da rifodero. L\u2019opera \ue8 stata posta sulla tavola a bassa pressione sulla quale era stato precedentemente steso un foglio di Melinex\uae. La miscela citocida \ue8 stata preparata al momento (0.3% di olio essenziale di Cinnamomum zeylanicum corteccia in idrolato di Citrus aurantium var amara fiori) ed \ue8 stata applicata a spruzzo dopo averla mescolata per bene in modo da ottenere un\u2019emulsione. Sono stati erogati 96 spruzzi per un totale di 300 ml di soluzione, ogni spruzzo aveva una capacit\ue0 di 3 ml e sono stati erogati da una distanza di circa 20 cm dall\u2019opera. Met\ue0 degli spruzzi sono stati distribuiti sul retro della tela e l\u2019altra met\ue0 su un foglio di carta assorbente, il quale \ue8 stato collocato a diretto contatto con il retro del dipinto. Per evitare la dispersione della soluzione biocida nell\u2019aria \ue8 stato disposto sull\u2019opera e sulla carta assorbente un foglio di Melinex\uae e tutto l\u2019insieme \ue8 stato chiuso con un nastro sigillante formando cos\uec un sacco. L\u2019opera \ue8 stata tenuta tutta la notte sotto peso, applicando per le prime 7 ore una temperatura di 30\ub0 C. Il giorno successivo il sacco \ue8 stato aperto, il foglio di carta assorbente \ue8 stato rimosso, sono stati eseguiti nuovamente i prelievi dei campioni che dall\u2019analisi microbiologica sono risultati privi di componenti microbiche. Infine, \ue8 stata azionata la tavola a bassa pressione cos\uec da permettere la totale evaporazione della poca umidit\ue0 rimasta. Dopo il trattamento biocida, attraverso un\u2019analisi visiva, la fibra della tela risultava omogenea e compatta, la superficie pittorica non presentava variazioni di tono e di saturazione cromatica e il trattamento eseguito non ha prodotto nessun cambiamento meccanico o estetico sul dipinto. Il tipo di trattamento citocida eseguito, oltre a mostrarsi efficace, non ha intralciato le successive fasi di restauro necessarie al dipinto ed \ue8 stato agevolmente gestito dall\u2019operator

New tools for the biological control of Xanthomonas fragariae in orchard

The angular leaf spot (ALS) disease caused by Xanthomonas fragariae (Xf) in strawberry is present in all growing areas seriously damaging the fruit quality. The Xf control mainly relies on preventive treatments with chemicals, such as copper-based products. Biological agents could represent an effective alternative within integrated control strategies. The antibacterial activity of two essential oil-based products (OEBPs) - VitiBioSap Plus® 1R45 and VitiBioSap Plus® 458 - was evaluated in orchard, by treatment with OEBPs against ALS, comparing it to the standard chemical treatments (control, SCT). In an orchard severely contaminated by Xf, in Emilia Romagna region (North-Central Italy), from August to November 2019, the OEBPs- or SCT-treatments were performed 13 times on plants belonging to five different cultivars (Asia, Malga, Roxana, Olympia and Tea). From October to November, three phytopathometric assessments were carried out to determine the leaf spot number to evaluate the disease severity (DS) using disease classes. At the first assessment, the DS resulted low in all OEBPs-treated cultivars. In particular, on cv. Asia, the OEBPs-treated plants showed a reduced DS compared to those SCT-treated, whereas on cvs. Malga and Roxana, the DS was higher with respect to that detected on SCT-treated plants. At the second and third assessments, the DS greatly increased in the orchard, but the OEBPs-treated plants of cvs. Asia, Malga, Roxana and Olympia showed a significantly reduced ALS severity compared to that of SCT-treated plants. During all the assessments, on cv. Tea the DS was low compared to the other cvs. regardless of treatment

Is the Antimicrobial Activity of Hydrolates Lower than That of Essential Oils?

Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to compare the antimicrobial activity of essential oils (EOs) and hydrolates (Hys) extracted from six aromatic plants grown in Italy (Lavandula angustifolia, Lavandula intermedia, Origanum hirtum, Satureja montana, Monarda didyma, and Monarda fistulosa) towards fungal (Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis; Trichophyton soudanense, Trichophyton tonsurans, Trichophyton rubrum, Trichophyton violaceum and Microsporum canis) and bacterial strains (Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Streptococcus pyogenes, E. faecalis, Enterococcus faecalis VRE, and Enterococcus faecium) potentially pathogenic for human skin. The composition and antimicrobial activity of EOs and Hys were evaluated using the Gas-chromatography mass spectrometry and micro dilution-broth test, respectively. The volatiles’ conversion factors (CFs) were calculated to compare the activity of Hys with that of the corresponding EOs. Data show that, although the minimum inhibitory concentration values of EOs are lower than the corresponding Hys, the volatiles contained in Hys are more effective at inhibiting microbial growth because they are active at lower concentrations

Essential Oils and Hydrolates: Potential Tools for Defense against Bacterial Plant Pathogens

The essential oils (EOs) of Origanum compactum and Satureja montana chemotyped (CT) at carvacrol, two Thymus vulgaris CT at thujanol and thymol, and Hydrolates (Hys) of S. montana and Citrus aurantium var. amara were chosen for studying their bactericidal efficacy against few phytobacterial pathogens. The Minimal Inhibitory Concentration (MIC) and Bactericidal Concentration (MBC) were found by microdilution assay. The essential oils of O. compactum (MBC 0.06% v/v), T. vulgaris CT thymol (MBC 0.06% v/v), and Hy of C. aurantium (MBC 6.25% v/v) resulted in being the most effective against Erwinia amylovora; thus, they were used as starting concentrations for ex vivo assays. Despite the great in vitro effectiveness, the disease incidence and the population dynamic ex vivo assays showed no significant results. On the other hand, EO of O. compactum and Hy of C. aurantium (at 0.03% and 4.5% v/v, respectively) showed resistance induction in tomato plants against Xanthomonas vesicatoria infections; both treatments resulted in approximately 50% protection. In conclusion, EOs and Hys could be promising tools for agricultural defense, but further studies will be necessary to stabilize the EOs emulsions, while Hys application could be an effective method to prevent bacterial diseases when used as resistance inducer by pre-transplantation treatment at roots

Anti-Mold Effectiveness of a Green Emulsion Based on Citrus aurantium Hydrolate and Cinnamomum zeylanicum Essential Oil for the Modern Paintings Restoration

A modern painting is characterized by multi-material bases extremely exposed to biodeteriogenic attacks. The aim of this work was to test the antifungal effectiveness of a natural, eco-friendly, and safe emulsion based on Citrus aurantium L. var. amara hydrolate and Cinnamomum zeylanicum Blume (from bark) essential oil, named “Zeylantium green emulsion” (Zege), on modern paintings. Colored unaged and aged canvas samples, performed with modern techniques (acrylic, vinylic and alkyd), were used to test in vitro both the antifungal effectiveness of Zege and its impact on the chemical–physical characteristics. Microbiological tests were performed according to the EUCAST international guidelines. pH measurements and colorimetric analysis were performed on unaged and aged canvases before and after Zege spray treatment. Finally, in situ tests were performed using the spray emulsion on canvas samples obtained from Ilaria Margutti’s modern artwork, which had been colonized by molds. Microbiological tests on canvas prototypes showed a time- and dose-dependent effectiveness of the Zege spray. None of the techniques underwent relevant changes in pH. Only the acrylic colors were unaffected in the colorimetric analysis, among all colored unaged or aged canvases. Tests made with modern artwork samples confirmed the in situ antifungal effectiveness. The Zege spray showed encouraging results in regard to the use of this formulation in the restoration of modern paintings

Il Silenzio: The First Renaissance Oil Painting on Canvas from the Uffizi Museum Restored with a Safe, Green Antimicrobial Emulsion Based on Citrus aurantium var. amara Hydrolate and Cinnamomum zeylanicum Essential Oil

Preserving artworks from the attacks of biodeteriogens is a primary duty of humanity. Nowadays, restorers use chemicals potentially dangerous for both artworks and human health. The purpose of this work was to find a green and safe formulation based on natural substances with fungicidal activity to restore ancient oil paintings, particularly “Il Silenzio” (by Jacopo Zucchi) preserved at the Uffizi Museum in Florence, Italy. The study was divided into two phases. First phase (in vitro study): three essential oils (EOs) and four hydrolates (Hys) were analysed by GC-mass spectrometry and in vitro tested against six ATCC strains of molds. An emulsion based on the more active natural compounds was tested on aged and unaged canvases samples to evaluate both their fungicidal activity and the impact on chemical-physical parameters. Finally, an in vivo toxicity test performed on the Galleria mellonella model assessed the safety for health. Second phase (in situ application): the emulsion was sprayed on the back of the painting and left to act for 24 h. Biodeteriogens present on the “Il Silenzio” painting were microbiologically identified before and after the treatment. The emulsion formulated with C. zeylanicum EO and C. aurantium var. amara Hy showed the best antifungal activity both in vitro and in situ without altering the chemical-physical characteristics of paintings. Furthermore, no in vivo toxicity was shown. For the first time, a green antimicrobial emulsion based on Hy and EO, safe for operators, was used to decontaminate an artwork colonised by fungi before the restoration practices

First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status

Background: Pembrolizumab is the first-line standard of care for advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score (TPS) >= 50%. Eastern Cooperative Oncology Group performance status (PS) 2 patients may receive pembrolizumab, despite the absence of sustaining evidence.Patients and methods: GOIRC-2018-01 is a multicentre, retrospective, observational study. PS 2 NSCLC patients with a PD-L1 TPS >= 50% receiving first-line pembrolizumab from June 2017 to December 2018 at 21 Italian institutions were included. Clinical-pathological characteristics were correlated with disease response and survival outcomes; adverse events were recorded. The primary objective was 6-months progression-free rate (6-months PFR).Results: One hundred fifty-three patients (median age 70 years) were enrolled. At a median follow-up of 18.2 months, median progression-free survival (PFS) and overall survival (OS) were 2.4 (95% confidence interval, 95% CI, 1.6-2.5) and 3.0 months (95% CI 2.4-3.5), respectively. 6-months PFR was 27% (95% CI 21-35%). Patients with a PS 2 determined by comorbidities (n = 41) had significantly better outcomes compared with disease burden-induced PS 2 (n = 112). Indeed, 6-months PFR was 49% versus 19%, median PFS 5.6 versus 1.8 months and OS 11.8 versus 2.8 months, respectively. Additional potential prognostic factors (radiotherapy, antibiotics, steroids received before pembrolizumab) correlated with clinical outcomes. The determinant of PS 2 resulted the only factor independently impacting on both PFS and OS. No toxicity issues emerged.Conclusions: Outcomes of PS 2 NSCLC patients with PD-L1 TPS >= 50% receiving first-line pembrolizumab were globally dismal but strongly dependent on the reason conditioning the poor PS itself. (C) 2020 Elsevier Ltd. All rights reserved