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

Trabecular bone score and bone turnover markers in men with DISH: Data from the Camargo Cohort study

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS). Methods: Cross-sectional study, nested in a prospective population-based cohort. All men (968) aged?50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed. Results: Mean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303-1.331] for DISH and 1.334 [1.327-1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI. Conclusions: TBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructureThe study has been funded by grants from the Instituto de Salud Carlos III (PI18/00762), Ministerio de Ciencia, Innovacion y Universidades, Spain, that included FEDER funds from the EU

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

Status and perspectives for low energy kaon-nucleon interaction studies at DAΦNE : from SIDDHARTA to SIDDHARTA-2

The study of the antikaon nucleon system at very low energies plays a key role for the understanding of the strong interaction between hadrons in the strangeness sector. The information provided by the low energy kaon- nucleon interaction is accessible through the study of kaonic atoms. The lightest atomic systems, namely the kaonic hydrogen and the kaonic deuterium, provide the isospin dependent kaon-nucleon scattering lengths by measuring the X-rays emitted during their de-excitation to the 1s level. Until now, the most precise kaonic hydrogen measurement and an exploratory measurement of kaonic deuterium were carried out at the DAΦNE collider by the SIDDHARTA collaboration, combining the excellent quality kaon beam delivered by the collider with new experimental techniques, as fast and very precise X-ray detectors, like the Silicon Drift Detectors. Today, the most important experimental information missing in the field of the low-energy antikaon-nucleon interactions is the experimental determination of the hadronic energy shift and width of kaonic deuterium, and will be measured by the new SIDDHARTA-2 experiment, which is installed in DAΦNE and is ready to start the data taking campaign

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

KAONIC HELIUM-4 L-SERIES YIELD MEASUREMENT AT 2.25 g/l DENSITY BY SIDDHARTA-2 at DAΦNE

This article presents the results of the kaonic helium-4 measurement conducted by the SIDDHARTA-2 experiment, aiming to provide crucial insights into the low-energy strong interaction in the strangeness sector. High-precision X-ray spectroscopy is used to examine the interaction between negatively charged kaons and nuclei in atomic systems. The SIDDHARTA-2 setup was optimized through the kaonic helium-4 measurement in preparation for the challenging kaonic deuterium measurement. The kaonic helium-4 measurement at a new density of 2.25 g/l is reported, providing the absolute and relative yields for the L-series transitions, which are essential data for understanding kaonic atom cascade processes

First measurement of kaonic helium-4 M-series transitions

In this paper we present the results of a new kaonic helium-4 measurement with a 1.37 g l−1 gaseous target by the SIDDHARTA-2 experiment at the DAΦNE collider. We measured, for the first time, the energies and yields of three transitions belonging to the M-series. Moreover, we improved by a factor about three, the statistical precision of the 2p level energy shift and width induced by the strong interaction, obtaining the most precise measurement for gaseous kaonic helium, and measured the yield of the Lα transition at the employed density, providing a new experimental input to investigate the density dependence of kaonic atoms transitions yield