Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.     

Neurotrophin Trk receptors in the brain of a teleost fish, Nothobranchius furzeri

Trk neurotrophin receptors are transmembrane tyrosine kinase proteins known as TrkA, TrkB, and TrkC. TrkA is the high affinity receptor for nerve growth factor, TrkB is the one for both brain-derived neurotrophic factor and neurotrophin-4, and TrkC is the preferred receptor for neurotrophin-3. In the adult mammalian brain, neurotrophins are important regulators of neuronal function and plasticity. This study is based on Nothobranchius furzeri, a teleost fish that is becoming an ideal candidate as animal model for aging studies because its life expectancy in captivity is of just 3 months. In adult N. furzeri, all three investigated neurotrophin Trk receptors were immunohistochemically detected in each brain region. TrkA positive neuronal perikarya were localized in the dorsal and ventral areas of the telencephalon and in the cortical nucleus; TrkB immunoreactivity was observed in neuronal perikarya of the dorsal and ventral areas of the telencephalon, the diffuse inferior lobe of the hypothalamus, and Purkinje cells; TrkC positive neuronal perikarya were detected in the most aboral region of the telencephalon, in the magnocellular preoptic nucleus and in few neurons dispersed in the hypothalamus. Numerous positive fibers were widely distributed throughout the brain. Radial glial cells lining the mesencephalic and rhombencephalic ventricles showed immunoreactivity to all three Trks. These findings suggest an involvement of neurotrophins in many aspects of biology of adult N. furzeri.     

Bagged Clustering and its application to tourism market segmentation

Aim of the paper is to propose a segmentation technique based on the Bagged Clustering (BC) method. In the partitioning step of the BC method, B bootstrap samples with replacement are generated by drawing from the original sample. The fuzzy C-medoids Clustering (FCMdC) method is run on each bootstrap sample, obtaining (B × C) medoids and the membership degrees of each unit to the different clusters. The second step consists in running a hierarchical clustering algorithm on the (B × C) medoids. The best partition of the medoids is obtained investigating properly the dendrogram. Then each unit is assigned to each cluster based on the membership degrees observed in the partitioning step. The effectiveness of the suggested procedure has been shown analyzing a suggestive tourism segmentation problem. We analyze two sample of tourists, each one attending a different cultural attraction, enlightening differences among clusters in socio-economic characteristics and in the motivational reasons behind visit behavior.     

Carboxymethylinulin–Chitosan Nanoparticles for the Delivery of Antineoplastic Mitoxantrone

Mitoxantrone (MTX) is an antineoplastic agent whose use is limited by serious side effects on non‐neoplastic cells. The aim of this study was the development of a new drug release system using an ionotropic gelation technique for microencapsulation of MTX in chitosan–carboxymethylinulin nanoparticles (CCInp), followed by evaluation of their cytotoxic effects on neoplastic MDA‐MB‐231 and non‐neoplastic NIH3T3 cell lines. The CCInp were prepared through a new reliable method for easy functionalization of both inulin and chitosan. Both unloaded and drug‐loaded nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) and showed a spherical morphology with an average hydrodynamic diameter between 40 and 80 nm. Both nanoparticles were stable and easily degraded by lysozyme. MTX‐loaded nanoparticles led to a greater mortality of MDA‐MB‐231 relative to free drug due to the ability of the nanoparticles to accumulate preferentially in neoplastic cells. The developed drug release system retains the ability to kill MDA‐MB‐231 cells in vitro, improving the survival of NIH3T3 cells.     

Single-shot biodiesel analysis: nearly instantaneous typification and quality control solely by ambient mass spectrometry

Using a simple and easily implemented desorption/ionization mass spectrometry technique, a tiny droplet of biodiesel placed on the surface of a sheet of paper is analyzed directly and nearly instantaneously under ambient conditions. No pre-separation or sample preparation is required, and clean mass spectra are obtained with great simplicity. In the positive ion mode, easy ambient sonic-spray ionization mass spectrometry, EASI(+)-MS, provides typical profiles of the major components of biodiesel samples, that is, either methyl esters (FAME) or ethyl esters (FAEE) of the natural fatty acids and triglycerides (TAG) from residual oil or oil from adulteration. Each FAME (FAEE) or TAG molecule is detected as a single sodiated molecule, [M + Na] (+) with relative intensities that correlate well with the known fatty acid profiles of the oil. Using EASI(-)-MS, typical and complementary profiles of free fatty acids (FFA) are obtained, which are detected in their deprotonated forms [FAA - H] (-). A general, single-shot approach for biodiesel analysis is therefore described, and samples from different feedstocks, from blends with petrodiesel, or from either methanol or ethanol trans-esterification are readily typified and major parameters of quality accessed.     

Local surface charges direct the deposition of carbon nanotubes and fullerenes into nanoscale patterns

This article reports on the directed deposition of carbon nanotubes (CNTs) and fullerenes onto solid surfaces using local electrostatic fields. Arbitrary patterns of local surface charges are created by charge writing with an atomic force microscope. During the subsequent development of the sample in an aqueous suspension containing surfactant-stabilized CNTs or fullerenes, Coulomb attraction guides the positioning and alignment of these particles onto the charge patterns. The surface potential of the charge patterns provides a direct control over the particle attachment. CNTs and fullerenes precisely reproduce the charge patterns, yielding structures with a lateral resolution down to the particle diameter.     

SCD – Stem Cell Differentiation Toward Osteoblast Onboard the International Space Station

Microgravity produces a variety of physical, chemical, and biological cues leading to an intricate and largely unresolved network of mechanosensitive molecules, transduction pathways, oxidative stress-related responses, and adaptations. The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends on the continuous remodelling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblast of mesenchymal origin. Focusing on osteogenic differentiation, we present the results of the ”SCD - Stem Cells Differentiation” experiment, aiming to determine how human bone marrow stem cells (hBMSCs) react to a prolonged (approx. 2 weeks) exposure to microgravity in terms of growth, and differentiation when treated with a physiological osteo-inducer as 1,25-dihydroxy vitamin D (Vit D3). The experiment was selected by the European Space Agency and transferred to ISS with the Soyuz-TMA- 16M (ISS 42S). It was carefully prepared because experiments performed on ISS remain a uniquely exceptional means of clarifying the microgravitational effects on osteogenesis, often only partially activated and detectable under simulated conditions. Because of the substantial reduction in calcification observed (about 50% inflight vs. on-ground control), we looked at significantly affected pathways in hBMSCs grown in microgravity vs. on-ground controls. Genome-wide expression changes were assessed via microarray and next generation sequencing (NGS) and integrated with exosomal mi-RNA measurements. Multi-scale pathway analysis of the omics datasets revealed evidence of cell cycle arrest, occurring with a number of osteogenic gene markers, but without indications of adipogenesis, senescence and/or apoptosis.     

Modeling,simulation and manufacturing of drill flutes

The designing of twist drill flutes (as well as that of end mills and of some combined tools) cannot be separated from the way they are manufactured. The aim of this paper is to present an intuitive direct method for modelling, simulation and manufacturing of the drill flutes with different shapes using conical grinding wheels with standardized shapes. The mathematical approach is described, which enables us to determine the flute profile in a section perpendicular to its axis as well as the manufacturing parameters. The grinding wheel has an initial position with respect to the cylindrical work piece, which is described using four parameters (Denavit Hartenberg parameters). We have presented algorithms in pseudocode that produce the flute shape and that compute the optimum parameters of the wheel position in the manufacturing process. Subsequently, a software application based on the aforementioned model is able to create visualizations of the flute shape. The analysis of the flute shape has enabled us to understand the influence of the geometrical parameters and the position of the grinding wheel on the resulting product in the grinding process. The order in which these parameters are to be set is also specified. We have built atlases of maps presenting the influence of the geometrical parameters and the position of the grinding wheel in the grinding process upon the shape of the flute. The validity of the method is proven by the agreement of the computed values with the input and output data produced by experiment. The proposed method allows helical flutes to be generated solely by using cylindrical and conical grinding wheels of standard shapes.