An integrated methodology for the analysis of collaboration in industry networks

In literature, a large number of studies on the Italian districts exhibit a portrait which points out the Italian economic specificity. A specific feature of the Italian districts is the large number of collaborative actions carried on by the associated enterprises which are not limited to the solution of the usual supply chain management problems. As not all the collaborative actions bring immediate (and measurable) economic benefits, there is the need for a reliable and unbiased method aimed at the identification and analysis of the collaborative patterns inside an industry network, to determine their presence and effectiveness. The proposed method uses a graph representation of the inter-firm relationships inside a network and induces the presence of collaborative behaviours by the analysis of the graph topology.     

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.     

Synthesis of poly(N‐isopropylacrylamide) by distillation precipitation polymerization and quantitative grafting on mesoporous silica

In this work, syntheses of thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) with different molecular weights were carried out in ethanol by distillation precipitation polymerization (DPP) technique. The synthesized polymers were fully characterized by attenuated total reflection Fourier‐transform infrared (ATR‐FTIR) spectroscopy, nuclear magnetic resonance spectroscopy, and size exclusion chromatography techniques. The lower critical solution temperatures of the polymers were determined with differential scanning calorimetry. A simple and versatile method for the in situ synthesis and grafting of PNIPAM on mesoporus silica nanoparticles (MSNs) with improved control over quantitative grafting is devised. The PNIPAM grafted MSNs were characterized with ATR‐FTIR, thermogravimetric analysis, transmission electron microscopy, and dynamic light scattering analyses. From the results obtained it is showed that quantitative grafting of PNIPAM on MSNs from 1 to 20% by weight can be tuned by manipulating the in situ DPP reaction conditions. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44181.     

Influence of Al2O3 on the performance of CeO2 used as catalyst in the direct carboxylation of methanol to dimethylcarbonate and the elucidation of the reaction mechanism

In this paper we show that modification of ceria by loading alumina strongly reduces the oxidation of methanol and the consequent reduction of Ce(IV) to Ce(III) with increase of both the life of the catalysts and their selectivity. The combination of surface techniques (XPS and BET) with structural techniques (XRD) has allowed a good characterisation of the working catalysts. Spectroscopic analyses (DRIFT and multinuclear solid state and solution NMR) have permitted the monitoring of the species formed on the surface of the catalyst and released from it. The formation of DMC takes place in successive steps such as (i) interaction of methanol with the catalyst surface with the formation of the surface-bound OCH₃; (ii) building on the catalyst surface of the hemicarbonate moiety [–OCH₃ → –OC(O)OCH₃]; and (iii) reaction of the latter with the gas-phase methanol to afford the organic carbonate.     

Clinical significance of erythrosedimentation rate in cancer in relation to cytokine production: correlation with high IL-6 and low IL-2 blood concentrations

Despite its well documented unfavourable prognostic significance in several human diseases, including cancer, the cytokinic mechanisms responsible for an increased erythrosedimentation rate (ESR) still remain to be better analyzed and defined. The recent possibility to measure cytokine concentrations in the blood of patients has allowed us to explore the possible relation between ESR values and endogenous cytokine secretions. This preliminary study was performed to evaluate the relationship between ESR values and serum levels of IL-2 and IL-6, which represent the most important cytokines responsible for the activation and the suppression, respectively, of host anticancer immune reaction. The study included 33 consecutive solid tumor patients, 22 of whom showed distant organ metastases. Abnormally high values of ESR were present in 21 patients, including 18/22 metastatic patients and 3/11 nonmetastatic patients. Patients with elevated values of ESR showed significantly higher mean levels of IL-6 and significantly lower mean concentrations of IL-2 with respect to those found in patients with normal ESR values. These results would show that cancer-related increase in ESR values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2 plays an essential role in the anticancer immunity and IL-6 may suppress the antitumor immune defenses, the evidence of low levels of IL-2 and high values of IL-6 in cancer patients with increased ESR values would explain the unfavourable prognostic significance of high ESR values in human neoplasms.     

Content of phytoestrogens in soy-based dietary supplements

The isoflavone content of 14 soy-based dietary supplements intended to help alleviate perimenopausal and menopausal symptoms on sale in Italy were analysed using HPLC with UV detection. The aim was to quantify soy isoflavones after hydrolysis as aglycones, which are the bioactive part of isoflavone molecules. In the examined products, the amounts of isoflavones were frequently expressed ambiguously, and none of the products stated whether the isoflavone content of the product was expressed as aglycones or as conjugates. Each product revealed a different aglycone concentration profile. These supplements have different “fingerprints”, probably due to different sources of raw materials and to methods used in processing and preparation of extracts. In more than half the supplements tested, the actual values contained were below those stated and below those expected to help alleviate perimenopausal and menopausal symptoms.     

A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia

The production of cytokines involved in platelet generation, including interleukin (IL)-3, IL-6 and IL-11, is stimulated by IL-2. However, the platelet number has been shown to decrease on IL-2 cancer therapy, and this side effect depends on the enhanced peripheral platelet destruction following the activation of the macrophage system by IL-2 itself. Our previous studies showed that IL-2-induced macrophage activation may be counteracted by the pineal hormone melatonin (MLT). On this basis, a pilot study with IL-2 plus MLT was performed to evaluate its influence on the platelet number in cancer patients with persistent thrombocytopenia. The study included 20 advanced solid tumor patients, who received IL-2 at 3 million IU/day s.c. for 6 days/week for 4 weeks in association with MLT (40 mg/day orally). A normalization of the platelet number was achieved in 14/20 (70%) patients. This pilot study shows that the therapy with low-dose IL-2 plus MLT, in addition to its previously described antitumor activity, may also be effective in the treatment of cancer-related thrombocytopenia.     

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.     

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy

Objective: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone.

Materials and methods: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application.

Results and discussion: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8?min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation.

Conclusions: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.     

Impact response of adhesive reversible joints made of thermoplastic nanomodified adhesive

The impact response of a reversible adhesive joint is experimentally assessed in this work. Joint reversibility is improved with a system that uses nanomodification of the thermoplastic adhesive used for bonding plastic components. This system, coupled with electromagnetic induction, is able to guarantee the separation of joints without any damage to the substrates. Drop dart tests at different impact velocities are carried out on neat and nanomodified bonded joints in order to compare the impact behavior before and after the introduction of nanoparticles. Experimental results show that the impact response, assessed in terms of peak load, absorbed energy, and flexural stiffness, can be affected by the introduction of nanoparticles. This work shows that adhesive nanomodified joints represent an effective and applicable solution for the reversible assembling of semi-structural components subjected to low-velocity impact loads.