THE COMPLEX RELATIONSHIP BETWEEN CHRONIC INFLAMMATION AND DIFFERENTIATED THYROID CANCER: EVIDENCE FROM IN VITRO AND CLINICAL STUDIES

Inflammation is an essential component of malignancies, including differentiated thyroid cancer (DTC). Thyroid cancer microenvironment is composed of a mixture of immune cells and soluble mediators. Among them, the chemokine CXCL8 exerts multiple pro-tumorigenic activities, including a chemotactic action on circulating neutrophils, induction of tumor cells growth, increase in angiogenesis and induction of the epithelial to mesenchymal transition, which promotes cell migration. Clinical studies in patients affected by several types of cancer evidenced that CXCL8 serum levels reflect the tumor burden and are related with the tumor aggressiveness. Solid evidence indicates that CXCL8 targeting can reduce tumor progression. The controversial relationship between inflammation and thyroid cancer tumorigenesis involves also the debated topic of the association between chronic-autoimmune-thyroiditis (CAT) and (DTC). DTCs are often diagnosed in the context of CAT and display an inflammatory-immune cells infiltration at histology, but whether the malignant transformation is promoted by the inflammatory response, or the peri-tumoral inflammation is induced by cancer-specific inflammatory molecules is still a matter of debate. This thesis project had two principal aims, i) to investigate the role of a pro-tumorigenic chemokine (CXCL8) in thyroid cancer microenvironment and to test in vitro the modulating properties of two different pharmacologic agents (PLX4720 and phenformin) and ii) to evaluate if CAT is a risk factor for the de novo development of DTC through a longitudinal population study. For Aim 1, thyroid cancer cell lines both BRAFV600E mutated (BCPAP, 8305C, 8505C) and RET/PTC rearranged (TPC-1), and normal human thyrocytes (NHT) were cultured alone or after treatment with two PLX4720 ore phenformin at increasing concentrations. CXCL8 concentrations were measured in the cell supernatants. Cell viability was evaluated through WST-1 and Annexin/propidium assay. Metastatic potential was assessed with migration assay and colony formation assay. For Aim 2, a retrospective longitudinal cohort study was designed including 510 CAT patients with a 10-years follow-up. The results of the first part of the thesis demonstrate that thyroid cancer cells secrete high amounts of CXCL8 and that both PLX4720 and phenformin are able to exert several anti-cancer activities within cancer microenvironment that are in part due to the inhibition of CXCL8 secretion. The results of the second part of the study indicate that the presence of CAT is not a risk factor for the new onset of DTC during long-term follow-up. The results of this thesis project suggest that two different kinds of inflammation (cancer-related and autoimmunity-related) exert different effects on DTC microenvironment and could have opposite effects on DTC development and prognosis

Privacy-preserving Overgrid: Secure Data Collection for the Smart Grid

In this paper we present a privacy-preserving scheme for Overgrid, a fully distributed peer-to-peer (P2P) architecture designed to automatically control and implement distributed Demand Response (DR) schemes in a community of smart buildings with energy generation and storage capabilities. To monitor the power consumption of the buildings, while respecting the privacy of the users, we extend our previous Overgrid algorithms to provide privacy preserving data aggregation ( extit{PP-Overgrid}). This new technique combines a distributed data aggregation scheme with the Secure Multi-Party Computation paradigm. First, we use the energy profiles of hundreds of buildings, classifying the amount of ``flexible'' energy consumption, i.e. the quota which could be potentially exploited for DR programs. Second, we consider renewable energy sources and apply the DR scheme to match the flexible consumption with the available energy. Finally, to show the feasibility of our approach, we validate the PP-Overgrid algorithm in simulation for a large network of smart buildin

Knee valgus in self-initiated vertical jump landings: developmental and gender comparisons

The study examined gender and developmental differences in knee valgus angle and external knee valgus moment at the time of maximal vertical ground reaction force (MGRFz) in self-initiated vertical jump (VJ) landings. Fifty-six subjects grouped by age (pre-pubescent (8-11 yrs); post-pubescent (19-29 yrs)) and gender jumped for a ball set at 50% of their maximum VJ height then landed on two feet with only their dominant foot on the force plate. Statistical analyses of motion analysis (3-D) and GRF data showed that children had greater valgus angles (p = .003) and moments (p = .026) at MGRFz compared to adults. Females had greater (p = .016) valgus moments than males, but similar valgus angles at MGRFz. It will be important to ensure that as both boys and girls progress through puberty they develop an ability to offset high valgus moments and land with good lower extremity alignment

Knee valgus in self-initiated vertical jump landings: developmental and gender comparisons

The study examined gender and developmental differences in knee valgus angle and external knee valgus moment at the time of maximal vertical ground reaction force (MGRFz) in self-initiated vertical jump (VJ) landings. Fifty-six subjects grouped by age (pre-pubescent (8-11 yrs); post-pubescent (19-29 yrs)) and gender jumped for a ball set at 50% of their maximum VJ height then landed on two feet with only their dominant foot on the force plate. Statistical analyses of motion analysis (3-D) and GRF data showed that children had greater valgus angles (p = .003) and moments (p = .026) at MGRFz compared to adults. Females had greater (p = .016) valgus moments than males, but similar valgus angles at MGRFz. It will be important to ensure that as both boys and girls progress through puberty they develop an ability to offset high valgus moments and land with good lower extremity alignment

Loading rate in self-initiated vertical jump landings: developmental and gender comparisons

The study compared gender and developmental differences in vertical loading rate upon a two-footed landing from a self-initiated VJ. Fifty-seven subjects grouped by age (pre-pubescent (8-11 yrs); post-pubescent (19-29 yrs)) and gender consented to participate. Subjects jumped for a ball set at 50% of their maximum VJ height, and landed on two feet, facing forward, with only their dominant foot on the force plate. Motion analysis (3-D) and ground reaction force (GRF) data were collected. Statistical analyses indicated significant developmental differences in vertical loading rate normalized to kinetic energy, but no gender differences. Children may have higher loading rates because they lack the experience, strength, and associated neuromuscular patterns that prepare them to modulate force as adults do

KNEE VALGUS IN SELF-INITIATED VERTICAL JUMP LANDINGS: DEVELOPMENTAL AND GENDER COMPARISIONS

The study examined gender and developmental differences in knee valgus angle and external knee valgus moment at the time of maximal vertical ground reaction force (MGRFz) in self-initiated vertical jump (VJ) landings. Fifty-six subjects grouped by age (pre-pubescent (8-11 yrs); post-pubescent (19-29 yrs)) and gender jumped for a ball set at 50% of their maximum VJ height then landed on two feet with only their dominant foot on the force plate. Statistical analyses of motion analysis (3-D) and GRF data showed that children had greater valgus angles (p = .003) and moments (p = .026) at MGRFz compared to adults. Females had greater (p = .016) valgus moments than males, but similar valgus angles at MGRFz. It will be important to ensure that as both boys and girls progress through puberty they develop an ability to offset high valgus moments and land with good lower extremity alignment

LOADING RATE IN SELF-INITIATED VERTICAL JUMP LANDINGS: DEVELOPMENTAL AND GENDER COMPARISONS

The study compared gender and developmental differences in vertical loading rate upon a two-footed landing from a self-initiated VJ. Fifty-seven subjects grouped by age (pre-pubescent (8-11 yrs); post-pubescent (19-29 yrs)) and gender consented to participate. Subjects jumped for a ball set at 50% of their maximum VJ height, and landed on two feet, facing forward, with only their dominant foot on the force plate. Motion analysis (3-D) and ground reaction force (GRF) data were collected. Statistical analyses indicated significant developmental differences in vertical loading rate normalized to kinetic energy, but no gender differences. Children may have higher loading rates because they lack the experience, strength, and associated neuromuscular patterns that prepare them to modulate force as adults do

Iodine status and supplementation in pregnancy: an overview of the evidence provided by meta-analyses

Iodine supplementation during pregnancy in areas with mild-moderate defciency is still a matter of debate. The present study aimed at systematically reviewing currently available evidences provided by meta-analyses with the aim to further clarify controversial aspects regarding the need of iodine supplementation in pregnancy as well as to provide guidance on clinical decision-making, even in areas with mild-moderate defciency. Medline, Embase and Cochrane search from 1969 to 2022 were performed. For the purpose of this review, only studies containing meta-analytic data were selected. A total of 7 meta-analyses were retrieved. Four meta-analyses evaluated the relationship between iodine status during pregnancy and neonatal and maternal outcomes suggesting the existence of a U-shaped correlation between iodine status and several maternal and neonatal consequences, especially if iodine status is evaluated at the beginning of pregnancy. Three meta-analyses evaluating the results of intervention trials failed to provide straightforward conclusions on the benefts of iodine supplementation in pregnant women in areas with mild-moderate iodine defciency. Although evidence coming from meta-analyses suggests a role of iodine status during pregnancy in determining maternal and child outcomes, results of meta-analyses of intervention trials are still controversial. Several factors including, degree of iodine defciency, and pooling studies conducted in areas with diferent iodine intake, may account for the lack of benefts reported by metaanalyses of intervention trials. More high-quality, randomized, controlled trials including information on timing, dose and regimen of iodine supplementation are needed to further elucidate this issue

An Indoor and Outdoor Navigation System for Visually Impaired People

In this paper, we present a system that allows visually impaired people to autonomously navigate in an unknown indoor and outdoor environment. The system, explicitly designed for low vision people, can be generalized to other users in an easy way. We assume that special landmarks are posed for helping the users in the localization of pre-defined paths. Our novel approach exploits the use of both the inertial sensors and the camera integrated into the smartphone as sensors. Such a navigation system can also provide direction estimates to the tracking system to the users. The success of out approach is proved both through experimental tests performed in controlled indoor environments and in real outdoor installations. A comparison with deep learning methods has been presented