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.     

Effects of PEMFC operating parameters on the performance of an integrated ethanol processor

In this paper the performance of a complete fuel cell system processing ethanol fuel has been analyzed as a function of the main fuel cell operating parameters. The fuel processor is based on the steam reforming process, followed by high- and low-temperature shift reactors, and carbon monoxide preferential oxidation reactor, which are coupled to a polymeric fuel cell (PEMFC). The goal was to analyze and improve the fuel cell system performance by simulation techniques. PEMFC operation has been analyzed using an available parametric model, which was implemented within HYSYS environment software. Pinch Analysis concepts were used to investigate the process energy integration and determine the maximum efficiency minimizing ethanol consumption. The system performance was analyzed for the SR-12 Modular PEM Generator, the Ballard Mark V fuel cell and the BCS 500 W stack. The net system efficiency is dependent on the required power demand. Efficiency values higher than 50% at low loads and less than 30% at high power demands are computed. In addition, the effect of fuel cell temperature, pressure and hydrogen utilization was analyzed. The trade-off between the reformer yield and the fuel cell performance defines the optimal operation pressure. The cell temperature determines operating zones where the water, involved in the reforming reactions, can be produced or demanded.     

Aorta transplantation in man: clinical and immunological studies

Aortic transplantation has progressively gained interest over the last few years and it is becoming a first choice indication in the substitution of infected prostheses. The most frequent complication in long-term vascular outcome (wall thickening, aneurysmatic dilation, stenosis), may occur through an immunological mechanism. In this study we investigated nine recipients, aged 48 to 65 years, of aorta segment replacement for anti-HLA antibody production (specificity and Ig class), CD3-CD4-CD8 T cell subpopulation dynamics and aorta wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were detected 1, 3 and 6 months after transplantation and persisted at a high concentration for at least 1 year. Furthermore, the absolute number of CD3, CD4 and CD8 positive lymphocytes increased progressively after aorta allograft. Tomography scanning showed a progressive thickness of the aorta wall. We can speculate that these anti-HLA antibodies in the recipients have the potential to harm the implant; therefore, aorta allograft should involve the induction of immunological tolerance by appropriate immunosuppressants.     

Morphological evaluation of bioartificial hydrogels as potential tissue engineering scaffolds

Poly(vinyl alcohol) hydrogels prepared by freeze-thawing procedure represent synthetic systems widely investigated as non-biodegradable scaffolds for tissue regeneration. In order to improve the biocompatibility properties of pure poly(vinyl alcohol) (PVA) hydrogels, blends of PVA with different biological macromolecules, such hyaluronic acid, dextran, and gelatin were prepared and used to produce bioartificial hydrogels. The porosity characteristics of these hydrogels were investigated by scanning electron microscopy and mercury intrusion porosimetry. The morphology of bioartificial hydrogels was evaluated and compared with that of pure PVA hydrogels. In particular the effect exerted by each biological component on pore size and distribution was investigated. The obtained results indicate that when a natural macromolecule is added to PVA the internal structure of the material changes. A small amount of biopolymer induces the structural elements of PVA matrix to take on a well evident lamellar appearance and an apparent preferential orientation. Comparing the results of SEM and mercury intrusion porosimetry it was concluded that hydrogels containing 20% of biological component have the most regular structure and at the same time the lowest total porosity. On the contrary samples with the highest content of natural polymer (40%) show the less regular structure and the highest total porosity.     

Volatile organic compounds in rural atmospheres of central Portugal

Atmospheric concentrations of volatile organic compounds were measured at two rural sites in central Portugal. The sites were chosen to be in line with the summer northwesterly sea breezes in order to study the evolution of the chemical composition of air masses during transport to inland areas. The most abundant non-oxygenated hydrocarbon in the ambient air was isoprene and the monoterpenes alpha-pinene, beta-pinene and 1,8 cineol. The maximum isoprene levels (6-7 ppb) were recorded at the most inland site, suggesting an enrichment of coastal air masses with biogenic emissions during transport over eucalyptus forests. Formaldehyde was the most prominent carbonyl compound in the atmosphere but acetaldehyde and acrolein were also abundant. Concentrations of carbonyl compounds had a tendency to be higher inland, particularly for glyoxal, methyl glyoxal, methyl vinyl ketone, metacrolein and pentanal. The observed increases indicate that carbonyls were produced by photochemical oxidation of biogenic hydrocarbons in aged air masses with coastal origin. Isoprene, monoterpenes and various carbonyls exhibited pronounced diurnal variations, which are explained on the basis of emissions from vegetation, oxidation pathways of biogenic hydrocarbons and meteorological conditions.     

Distributed Databases for the development of Mechanisms Topology

In this paper different types of data structures for database modeling are reviewed in order to suggest the one which most suits the needs of a database management system dedicated to the study of the mechanical systems. Topology is proposed as the classification criterion, this inspiration being due to the separation of the concepts of structure and function, as proposed for the first time by Freudenstein and Maki [Environ. Planning B 6 (1979) 375–391]. An example of a local database is herein presented and, finally, the adopted codes are briefly commented upon which, on the base of the evaluation of the power of the adjacency matrices, identify the kinematic chains (KCs) and mechanisms.     

A brief note on the concept of planarity for kinematic chains

In this note the concept of planarity is briefly reviewed with the aim of suggesting a unified interpretation of this word as an attribute of the concept of kinematic chain. The lack of a correct and unambiguous meaning of the concept of planar kinematic chain may cause serious misunderstandings nowadays, as in the reported example.     

Universals and cultural differences in the judgments of facial expressions of emotion.

We present here new evidence of cross-cultural agreement in the judgment of facial expression. Subjects in 10 cultures performed a more complex judgment task than has been used in previous cross-cultural studies. Instead of limiting the subjects to selecting only one emotion term for each expression, this task allowed them to indicate that multiple emotions were evident and the intensity of each emotion. Agreement was very high across cultures about which emotion was the most intense. The 10 cultures also agreed about the second most intense emotion signaled by an expression and about the relative intensity among expressions of the same emotion. However, cultural differences were found in judgments of the absolute level of emotional intensity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)