Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.     

Design and control of an IPMC wormlike robot.

This paper presents an innovative wormlike robot controlled by cellular neural networks (CNNs) and made of an ionic polymer-metal composite (IPMC) self-actuated skeleton. The IPMC actuators, from which it is made of, are new materials that behave similarly to biological muscles. The idea that inspired the work is the possibility of using IPMCs to design autonomous moving structures. CNNs have already demonstrated their powerfulness as new structures for bio-inspired locomotion generation and control. The control scheme for the proposed IPMC moving structure is based on CNNs. The wormlike robot is totally made of IPMCs, and each actuator has to carry its own weight. All the actuators are connected together without using any other additional part, thereby constituting the robot structure itself. Worm locomotion is performed by bending the actuators sequentially from "tail" to "head," imitating the traveling wave observed in real-world undulatory locomotion. The activation signals are generated by a CNN. In the authors' opinion, the proposed strategy represents a promising solution in the field of autonomous and light structures that are capable of reconfiguring and moving in line with spatial-temporal dynamics generated by CNNs.     

SEL: A unified algorithm for salient entity linking

The entity linking task consists in automatically identifying and linking the entities mentioned in a text to their uniform resource identifiers in a given knowledge base. This task is very challenging due to its natural language ambiguity. However, not all the entities mentioned in the document have the same utility in understanding the topics being discussed. Thus, the related problem of identifying the most relevant entities present in the document, also known as salient entities (SE), is attracting increasing interest. In this paper, we propose salient entity linking, a novel supervised 2‐step algorithm comprehensively addressing both entity linking and saliency detection. The first step is aimed at identifying a set of candidate entities that are likely to be mentioned in the document. The second step, besides detecting linked entities, also scores them according to their saliency. Experiments conducted on 2 different data sets show that the proposed algorithm outperforms state‐of‐the‐art competitors and is able to detect SE with high accuracy. Furthermore, we used salient entity linking for extractive text summarization. We found that entity saliency can be incorporated into text summarizers to extract salient sentences from text. The resulting summarizers outperform well‐known summarization systems, proving the importance of using the SE information.     

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Discordance Rate of HER2 Status in Primary Gastric Carcinomas and Synchronous Lymph Node Metastases: A Multicenter Retrospective Analysis

Background: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. Materials and Methods: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. Results: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. Conclusions: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.     

Monitoring the oxidative modification of lipoprotein(a) by capillary zone electrophoresis

Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease. It is made of a lipoprotein particle containing apoB100 linked by a single disulfide bridge to apolipoprotein(a), a glycosylated protein with a variable mass. Some authors suggest that oxidative modification could explain the contribution of Lp(a) in the development of atheromatous lesions in a comparable way to low‐density lipoproteins (LDL). Recently, the use of capillary electrophoresis to measure the variations in the relative electrophoretic mobility (REM) of LDL subjected to copper oxidation has been proposed. The aim of this work is to employ this method also to monitor the copper‐induced oxidative modification of Lp(a). Migration of Lp(a) was monitored by absorption at 200 nm in a 50 mmol/L tricine, 100 mmol/L methylglucamine, pH 9.7 run buffer. Contrary to the conventional slab gel methods, our procedure provides a rapid and reproducible means to measure the electrophoretic mobility of Lp(a) (migration time <10 min with a CV% <0.5).     

Cushing’s Syndrome Effects on the Thyroid

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.     

Design and evaluation of a multimedia storage server for mixed traffic

The relative simplicity of access to digital communications nowadays and the simultaneous increase in the available bandwidth are leading to the definition of new telematic services, mainly oriented towards multimedia applications and interactivity with the user. In the near future, a decisive role will be played in this scenario by the providers of interactive multimedia services of the on-demand type, which will guarantee the end user a high degree of flexibility, speed and efficiency. In this paper, some of the technical aspects regarding these service providers are dealt with, paying particular attention to the problems of storing information and managing service requests. More specifically, the paper presents and evaluates a new storage technique based on the use of disk array technology, which can manage both typical multimedia connections and traditional requests. The proposed architecture is based on the joint use of the partial dynamic declustering and the information dispersal algorithm, which are employed for the allocation and retrieval of the data stored on the disk array. We also define efficient strategies for request management in such a way as to meet the time constraints imposed by multimedia sessions and guarantee good response times for the rest of the traffic. The system proposed is then analyzed using a simulation approach.