Prognostic and therapeutic role of angiogenic microenvironment in thyroid cancer

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target

The critical view of safety during laparoscopic cholecystectomy: Strasberg Yes or No? An Italian Multicentre study

Background: Laparoscopic cholecystectomy is considered the gold standard for the treatment of gallbladder lithiasis; nevertheless, the incidence of bile duct injuries (BDI) is still high (0.3–0.8%) compared to open cholecystectomy (0.2%). In 1995, Strasberg introduced the "Critical View of Safety" (CVS) to reduce the risk of BDI. Despite its widespread use, the scientific evidence supporting this technique to prevent BDI is controversial. Methods: Between March 2017 and March 2019, the data of patients submitted to laparoscopic cholecystectomy in 30 Italian surgical departments were collected on a national database. A survey was submitted to all members of Italian Digestive Pathology Society to obtain data on the preoperative workup, the surgical and postoperative management of patients and to judge, at the end of the procedure, if the isolation of the elements was performed according to the CVS. In the case of a declared critical view, iconographic documentation was obtained, finally reviewed by an external auditor. Results: Data from 604 patients were analysed. The study population was divided into two groups according to the evidence (Group A; n = 11) or absence (Group B; N = 593) of BDI and perioperative bleeding. The non-use of CVS was found in 54.6% of procedures in the Group A, and 25.8% in the Group B, and evaluating the operator-related variables the execution of CVS was associated with a significantly lower incidence of BDI and intraoperative bleeding. Conclusions: The CVS confirmed to be the safest technique to recognize the elements of the Calot triangle and, if correctly performed, it significantly impacted on preventing intraoperative complications. Additional educational programs on the correct application of CVS in clinical practice would be desirable to avoid extreme conditions that may require additional procedures

Novel Machine Learning and Differentiable Programming Techniques applied to the VIP-2 Underground Experiment

In this work, we present novel Machine Learning and Differentiable Programming enhanced calibration techniques used to improve the energy resolution of the Silicon Drift Detectors (SDDs) of the VIP-2 underground experiment at the Gran Sasso National Laboratory (LNGS). We achieve for the first time a Full Width at Half Maximum (FWHM) in VIP-2 below 180 eV at 8 keV, improving around 10 eV on the previous state-of-the-art. SDDs energy resolution is a key parameter in the VIP-2 experiment, which is dedicated to searches for physics beyond the standard quantum theory, targeting Pauli Exclusion Principle (PEP) violating atomic transitions. Additionally, we show that this method can correct for potential miscalibrations, requiring less fine-tuning with respect to standard methods.Comment: Submitted to Measurement Science and Technolog

Towards the first kaonic deuterium measurement with the SIDDHARTA-2 experiment at DAΦNE

The SIDDHARTA-2 experiment is going to perform the longawaited high precision X-ray measurement of kaonic deuterium, obtaining for the first time the values of the shift and the width induced by the strong interaction on the fundamental level. By combining this unprecedented result with the analogous kaonic hydrogen measurement performed by the SIDDHARTA experiment, it will be possible to extract the isospin-dependent antikaon-nucleon scattering lengths, providing direct information on the Quantum Chromodynamics (QCD) in the non-perturbative Chromodynamics (QCD) in the non-perturbative regime in the strangeness sector. This paper describes the SIDDHARTA-2 experiment, presently installed at the DAΦNE collider of Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, and the results obtained during the kaonic helium run, preparatory for the kaonic deuterium data taking campaign planned for 2022

CdZnTe detectors tested at the DA{\Phi}NE collider for future kaonic atoms measurements

The SIDDHARTA-2 collaboration at the INFN Laboratories of Frascati (LNF) aims to perform groundbreaking measurements on kaonic atoms. In parallel and beyond the ongoing kaonic deuterium, presently running on the DA$\Phi$NE collider at LNF, we plan to install additional detectors to perform further kaonic atoms' studies, taking advantage of the unique low energy and low momentum spread $K^-$ beam delivered by the at-rest decay of the $\phi$ meson. CdZnTe devices are ideal for detecting transitions toward both the upper and lower levels of intermediate-mass kaonic atoms, like kaonic carbon and aluminium, which have an important impact on the strangeness sector of nuclear physics. We present the results obtained in a set of preliminary tests conducted on DA$\Phi$NE, in view of measurements foreseen in 2024, with the twofold aim to tune the timing window required to reject the extremely high electromagnetic background, and to quantify the readout electronics saturation effect due to the high rate, when placed close to the Interaction Region (IR). In the first test we used commercial devices and electronics, while for the second one both were customized at the IMEM-CNR of Parma and the University of Palermo. The results confirmed the possibility of finding and matching a proper timing window where to identify the signal events and proved better performances, in terms of energy resolution, of the custom system. In both cases, strong saturation effects were confirmed, accounting for a loss of almost 90\% of the events, which will be overcome by a dedicated shielding structure foreseen for the final experimental setup

A new kaonic helium measurement in gas by SIDDHARTINO at the DAFNE collider*

The SIDDHARTINO experiment at the DA{\Phi}NE Collider of INFN-LNF, the pilot run for the SIDDHARTA-2 experiment which aims to perform the measurement of kaonic deuterium transitions to the fundamental level, has successfully been concluded. The paper reports the main results of this run, including the optimization of various components of the apparatus, among which the degrader needed to maximize the fraction of kaons stopped inside the target, through measurements of kaonic helium transitions to the 2p level. The obtained shift and width values are {\epsilon}_2p = E_exp-E_e.m = 0.2 {\pm} 2.5(stat) {\pm} 2(syst) eV and {\Gamma}_2p = 8 {\pm} 10 eV (stat), respectively. This new measurement of the shift, in particular, represents the most precise one for a gaseous target and is expected to contribute to a better understanding of the kaon-nuclei interaction at low energy

Characterization of the SIDDHARTA-2 luminosity monitor

A luminosity monitor, based on plastic scintillator detectors, has been developed for the SIDDHARTA-2 experiment aiming to perform high precision measurements of kaonic atoms and was installed in 2020 on the DAFNE $e^+e^-$ collider at LNF (Laboratori Nazionali di Frascati, INFN). The main goal of this system is to provide the~instantaneous and integrated luminosity of the DAFNE facility by measuring the rate of $K^+K^-$ correlated pairs emitted by the phi meson decay. This task requires an accurate timing of the DAQ signals, as well as timing resolution below 1ns, in order to disentangle the $K^\pm$ signals from the background minimum ionizing particles (MIPs) produced during the $e^+e^-$ collisions at DAFNE. In this paper the luminosity monitor concept as well as its laboratory characterization and the first results inside DAFNE are presented.Comment: Published in JINS

Potentialities of CdZnTe Quasi-Hemispherical Detectors for Hard X-ray Spectroscopy of Kaonic Atoms at the DAΦNE Collider

Kaonic atom X-ray spectroscopy is a consolidated technique for investigations on the physics of strong kaon-nucleus/nucleon interaction. Several experiments have been conducted regarding the measurement of soft X-ray emission (<20 keV) from light kaonic atoms (hydrogen, deuterium, and helium). Currently, there have been new research activities within the framework of the SIDDHARTA-2 experiment and EXCALIBUR proposal focusing on performing precise and accurate measurements of hard X-rays (>20 keV) from intermediate kaonic atoms (carbon, aluminum, and sulfur). In this context, we investigated cadmium-zinc-telluride (CdZnTe or CZT) detectors, which have recently demonstrated high-resolution capabilities for hard X-ray and gamma-ray detection. A demonstrator prototype based on a new cadmium-zinc-telluride quasi-hemispherical detector and custom digital pulse processing electronics was developed. The detector covered a detection area of 1 cm2 with a single readout channel and interesting room-temperature performance with energy resolution of 4.4% (2.6 keV), 3% (3.7 keV), and 1.4% (9.3 keV) FWHM at 59.5, 122.1, and 662 keV, respectively. The results from X-ray measurements at the DAΦNE collider at the INFN National Laboratories of Frascati (Italy) are also presented with particular attention to the effects and rejection of electromagnetic and hadronic background