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

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

Revised Selection Criteria for Candidate Restriction Enzymes in Genome Walking

A new method to improve the efficiency of flanking sequence identification by genome walking was developed based on an expanded, sequential list of criteria for selecting candidate enzymes, plus several other optimization steps. These criteria include: step (1) initially choosing the most appropriate restriction enzyme according to the average fragment size produced by each enzyme determined using in silico digestion of genomic DNA, step (2) evaluating the in silico frequency of fragment size distribution between individual chromosomes, step (3) selecting those enzymes that generate fragments with the majority between 100 bp and 3,000 bp, step (4) weighing the advantages and disadvantages of blunt-end sites vs. cohesive-end sites, step (5) elimination of methylation sensitive enzymes with methylation-insensitive isoschizomers, and step (6) elimination of enzymes with recognition sites within the binary vector sequence (T-DNA and plasmid backbone). Step (7) includes the selection of a second restriction enzyme with highest number of recognition sites within regions not covered by the first restriction enzyme. Step (8) considers primer and adapter sequence optimization, selecting the best adapter-primer pairs according to their hairpin/dimers and secondary structure. In step (9), the efficiency of genomic library development was improved by column-filtration of digested DNA to remove restriction enzyme and phosphatase enzyme, and most important, to remove small genomic fragments (<100 bp) lacking the T-DNA insertion, hence improving the chance of ligation between adapters and fragments harbouring a T-DNA. Two enzymes, NsiI and NdeI, fit these criteria for the Arabidopsis thaliana genome. Their efficiency was assessed using 54 T3 lines from an Arabidopsis SK enhancer population. Over 70% success rate was achieved in amplifying the flanking sequences of these lines. This strategy was also tested with Brachypodium distachyon to demonstrate its applicability to other larger genomes

Studies of the linearity and stability of silicon drift detectors for kaonic atoms X-ray spectroscopy

The SIDDHARTA-2 experiment at the DAFNE collider aims to perform precision measurements of kaonic atoms X-ray spectroscopy for the investigation of the antikaon?nucleon strong interaction. To achieve this goal, novel large-area Silicon Drift Detectors (SDDs) have been developed. These devices have special geometry, field configuration, and readout electronics that ensure excellent performance in terms of linearity and stability. The paper presents preliminary results for the linearity determination and stability monitoring of the SDDs system during the measurement of kaonic deuterium carried out in the summer of 2022

SIDDHARTA-2 apparatus for kaonic atoms research on the DAΦ\PhiNE collider

SIDDHARTA-2 represents a state-of-the-art experiment designed to perform dedicated measurements of kaonic atoms, which are particular exotic atom configurations composed of a negatively charged kaon and a nucleus. Investigating these atoms provides an exceptional tool to comprehend the strong interactions in the non-perturbative regime involving strangeness. The experiment is installed at the DA$\Phi$NE electron-positron collider, of the INFN National Laboratory of Frascati (INFN-LNF) in Italy, aiming to perform the first-ever measurement of the 2p$\rightarrow$1s X-ray transitions in kaonic deuterium, a crucial step towards determining the isospin-dependent antikaon-nucleon scattering lengths. Based on the experience gained with the previous SIDDHARTA experiment, which performed the most precise measurement of the kaonic hydrogen 2p$\rightarrow$1s X-ray transitions, the present apparatus has been upgraded with innovative Silicon Drift Detectors (SDDs), distributed around a cryogenic gaseous target placed in a vacuum chamber at a short distance above the interaction region of the collider. We present a comprehensive description of the SIDDHARTA-2 setup including the optimization of its various components during the commissioning phase of the collider.Comment: 32 pages, 21 figure

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

Main features of the SIDDHARTA-2 apparatus for kaonic deuterium X-ray measurements

The low-energy, non-perturbative regime of QCD can be studied directly by X-ray spectroscopy of light kaonic atoms. The SIDDHARTA-2 experiment, located at the DAΦNE collider, aims to measure the 2p $\to$ 1s transition in kaonic deuterium for the first time to extract the antikaon-nucleon scattering lengths. This measurement is impeded, inter alia, by the low K$^{-}$d X-ray yield. Hence, several updates have been implemented on the apparatus to increase the signal-to-background ratio, which are discussed in detail in this paper: a lightweight gas target cell, novel Silicon Drift Detectors for the X-ray detection with excellent performance, and a veto system for active background suppression. The experiment has undergone a first preparatory run during DAΦNE’s commissioning phase in 2021, concluding with a successful kaonic helium measurement