Università degli Studi di Genova

As part of the research project called FCC-hh led by CERN, which aims to study the possibility of building a new 100 TeV center of mass energy particle collider along an 80-100 km circumference tunnel, there are many collaborations underway to test different designs for the main bending dipole of the collider. One of these collaborations involves INFN, the Italian Institute of Nuclear Physics, which has been working on the cos $\theta$ design until 2019 as part of the European EuroCirCol project. This study consisted of a conceptual design of a 16 T, double-aperture, four-layer dipole made of Nb $_{3}$ Sn. Considering the challenge that such a cutting-edge magnet represents, this conceptual design resulted in a 5-year agreement between INFN and CERN in order to study and build a 1.5 m long, single aperture, cos $\theta$ , Nb $_{3}$ Sn dipole with a target magnetic field of 12 T. This project is called the Future Accelerator post-LHC Cos $\theta$ Optimized Nb $_{3}$ Sn Dipole (or FalconD for short). In this paper we present the mechanical analysis of this project after some major cross-sectional upgrades that have impacted the design by easing the assembly phase. One of the most challenging aspects of this design is its mechanical structure that must handle the intense magnetic forces generated by such a high magnetic field. The mechanical structure is based on the “bladder & key” (B&K) concept and it has never been adopted before in a cos $\theta$ dipole, so it needs to be validated. This contribution presents the 2D FEM of the FalconD, showing the mechanical behavior of the magnet during each construction step.

The Future Circular Collider in hadron-hadron configuration (FCC-hh) is one of the main options for the post-LHC era of particle accelerator. The project led by CERN aims to build a 100 km-long collider with 100 TeV of center-of-mass energy, using bending dipoles able to achieve a bore field $>$ 14 T. The Istituto Nazionale di Fisica Nucleare (INFN) and CERN are collaborating to construct a Nb $_{3}$ Sn cos-theta dipole model, to increase the R&D efforts for high-field superconducting magnets technology, according to the updated European Strategy for Particle Physics. Here we give an update on the intense design activity, and we report the results of the first winding trials performed with a dummy conductor, to experimentally validate the magnet design and start the iterative process to optimize the manufacturing method. The results of the first winding tests are shown in the paper, focusing on the impact of the coiling procedure on the mechanical behavior of the unreacted Nb $_{3}$ Sn Rutherford cable.

The MBRD (Main Bending Recombination Dipole, or D2) is one of the magnets in the interaction region of the LHC that needs to be replaced in order to fulfill the requirements of the High-Luminosity upgrade. The magnetic field must be increased up to 4.5 T in an aperture with a diameter of 105 mm and a total length of about 8 m, to reach the target integrated field of 35 T $\cdot$ m. The increase of the magnetic field and, consequently, of the cross talk between the two apertures having the same polarity required a brand-new design characterized by asymmetric left-right coils and aluminum rings around the two apertures in order to compensate the repulsive Lorentz forces arising between them. The design was carried out at INFN, while the construction is taking place at the ASG Superconductors (Genova, Italy). The development plan was to initially build a 1.6 m long model, completed and cold tested in summer 2020, a full scale prototype, whose cold tests are now ongoing, followed by a series of six magnets, presently under construction. The test campaign performed on the short model and the one currently underway on the prototype provide very useful information for the magnets of the series, such as the behavior of the protection circuit in case of quenches. During the measurements performed at CERN, several quenches induced by the quench heaters were provoked, and the magnet behavior was recorded for different initial currents. This contribution will focus on the results of such tests and their comparison with the predictions obtained through the simulations with two different codes, Roxie and STEAM-LEDET.

Iridium films grown by pulsed laser deposition (PLD) show different critical temperatures ( T_c ), which can be almost twice the T_c of the bulk. This difference is related to the thickness and deposition conditions. To understand this effect, we grew different films with different configuration parameters: laser focusing, distance to the Ir target, and deposition time. We then measured the T_c and analyzed the film with structural measurements by X-ray diffraction (XRD), looking at a possible correlation with the grain size of the film itself. The work was performed to determine the film growth conditions at which it is possible to obtain predetermination of T_c with good accuracy using XRD pattern characteristics of Ir films.

In oceanic ecosystems, the nature of barriers to gene flow, and the processes by which populations may become isolated are different from the terrestrial environment, and less well understood. In this study we investigate a highly mobile species (the sperm whale, Physeter macrocephalus) that is genetically differentiated between an open North Atlantic population and the populations in the Mediterranean Sea. We apply high resolution single nucleotide polymorphism (SNP) analysis to study the nature of barriers to gene flow in this system, assessing the putative boundary into the Mediterranean (Strait of Gibraltar and Alboran Sea region), and including novel analyses on structuring among sperm whale populations within the Mediterranean basin. Our data support a recent founding of the Mediterranean, around the time of the last glacial maximum, and show concerted historical demographic profiles in both the Atlantic and in the Mediterranean. In each region there is evidence for a population decline around the time of the founder event. The largest decline was seen within the Mediterranean Sea where effective population size is substantially lower (especially in the eastern basin). While differentiation is strongest at the Atlantic/Mediterranean boundary, there is also weaker but significant differentiation between the eastern and western basins of the Mediterranean Sea. We propose, however, that the mechanisms are different. While post‐founding gene flow was reduced between the Mediterranean and Atlantic populations, within the Mediterranean an important factor differentiating the basins is likely a greater degree of admixture between the western basin and the North Atlantic and some level of isolation between the western and eastern Mediterranean basins. Subdivision within the Mediterranean Sea exacerbates conservation concerns and will require consideration of what distinct impacts may affect populations in the two basins.

Celiac disease (CD) is an autoimmune disease with inflammatory characteristics, having a condition of chronic malabsorption, affecting approximately 1% of the population at any age. In recent years, a concrete correlation between eating disorders and CD has emerged. Hypothalamus plays a central role in determining eating behaviour, regulating appetite and, consequently, food intake. One hundred and ten sera from celiac patients (40 active and 70 following a gluten-free diet) were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. In addition, ghrelin was measured by ELISA. As control, 45 blood serums from healthy age matched were analysed. Among active CD, all patients resulted positive for anti-hypothalamus autoantibodies and sera showed significantly higher levels of ghrelin. All of the free-gluten CD were negative for anti-hypothalamus autoantibodies and had low levels of ghrelin, as well as healthy controls. Of interest, anti-hypothalamic autoantibodies directly correlate with anti-tTG amounts and with mucosal damage. In addition, competition assays with recombinant tTG showed a drastically reduction of anti-hypothalamic serum reactivity. Finally, ghrelin levels are increased in CD patients and correlated with anti-tTG autoantibodies and anti-hypothalamus autoantibodies. This study demonstrates for the first time the presence of anti-hypothalamus antibodies and their correlation with the severity of the CD. It also allows us to hypothesize the role of tTG as a putative autoantigen expressed by hypothalamic neurons.

Objective: To investigate the frequency and trajectories of individual patients with polyarticular-course juvenile idiopathic arthritis (pJIA) achieving novel composite endpoints on abatacept. Methods: Data from a clinical trial of subcutaneous abatacept (NCT01844518) and a post hoc analysis of intravenous abatacept (NCT00095173) in patients with pJIA were included. Three endpoints were defined and evaluated; combined occurrence of low disease activity (LDA) measured by the Juvenile Arthritis Disease Activity Score, 50% improvement in JIA-American College of Rheumatology criteria (ACR50), and patient-reported outcomes (PRO). PROs included visual analog scale (VAS) of minimal pain (pain-min) and Childhood Health Assessment Questionnaire-disability index score of 0 (CHAQ-DI0). In this post hoc analysis, maintenance of month 13 and 21 endpoints (LDA+pain-min, LDA+CHAQ-DI0, and ACR50+pain-min) in those who achieved them at month 4 was determined. Results: Composite endpoints (LDA+pain-min, LDA+CHAQ-DI0, and ACR50+pain-min) were achieved at month 4: 44.7%, 19.6%, and 58.9% of the 219 patients treated with SC abatacept, respectively. Of those who achieved LDA+pain-min at month 4, 84.7% (83/98) and 65.3% (64/98) maintained LDA+pain-min at months 13 and 21, respectively. The proportions of patients meeting LDA+pain-min outcomes increased from 44.7% (98/219) at month 4 to 54.8% (120/219) at month 21. The frequency of patients who met LDA+CHAQ-DI0 increased from 19.6% (43/219) at month 4 to 28.8% (63/219) at month 21. Conclusions: Among individual patients with pJIA treated with abatacept who achieved one of the combined clinical and PRO composite endpoints, many maintained them over 21 months of abatacept treatment.

Unlabelled: Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination (PE). Although ultrasound (US) allows discrimination of the two entities, only definitions and scoring of synovitis in children have been established. Objective: To produce consensus-based US definitions of tenosynovitis in JIA. Methods: A systematic literature search was performed. Selection criteria included studies focused on US definition and scoring systems for tenosynovitis in children, as well as US metric properties. Through a 2-step Delphi process, a panel of international US experts developed definitions for tenosynovitis components (step 1) and validated them by testing their applicability on US images of tenosynovitis in several age groups (step 2). A 5-point Likert scale was used to rate the level of agreement. Results: Fourteen studies were identified. Most used the US definitions developed for adults to define tenosynovitis in children. Construct validity was reported in 86% of articles using as comparator PE. Few studies reported US reliability and responsiveness in JIA. In step 1, experts reached a strong group agreement (>86%) by applying adult definitions to children after one round. After 4 rounds of step 2, the final definitions were validated on all tendons and at all locations, except for biceps tenosynovitis in children under 4 years. Conclusion: The study shows that the definition of tenosynovitis used in adults is applicable to children with minimal modifications agreed upon through a Delphi process. Further studies are required to confirm our results. This article is protected by copyright. All rights reserved.

The final phases of the information systems lifecycle are no less important than the initial ones. However, previous research indicated a lack of studies on information systems discontinuance. This paper aims to verify whether this gap still exists by analysing the literature on enterprise resource planning (ERP) systems, a type of software widely used in many organisations. To identify the relevant literature, the paper involved searching in Scopus and Web of Science databases. Despite several ERP literature reviews suggesting more studies on the retirement phase and no time limits in the search, very few studies have been identified. To sketch the current state of knowledge on the selected topic, the paper developed a scoping review and, based on the results, comments on possible critical issues. The work supports researchers and practitioners interested in information systems discontinuance, as it provides some considerations to develop future research. In addition, it has practical implications because the advancement of the knowledge frontier will help organizations cope with this kind of change.

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. material 1.

The article reports on the design and piloting of the MobIta proficiency test. MobIta was designed as an entry test for a course of Italian for Business Purposes to assess reading and writing skills in the occupational and public domains of the Common European Framework. However, since the course was entirely online, we included in our test a part devoted to assessing language proficiency for online learning. After contextualising linguistic competence for online education, the paper illustrates the development of the test, focusing on the piloting stage. We conclude that language proficiency is an important asset for distance education and, since it can hinder the learners’ participation, must therefore be carefully considered.

Background After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology.Objectives To provide guidance for clinicians in daily practice for areas in which there is limited guidance.MethodsA Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings.ResultsConsensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements.Conclusions In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients’ risk factors and carry out proper monitoring during the course of treatment.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Background: The thoracic area has mainly been neglected in research compared to the lumbar and cervical regions. No clinical practice guidelines (CPGs) for non-specific thoracic spine pain (TSP) have been compiled. Therefore, it can be argued that the absence of specific CPGs raises questions about the management of non-specific TSP. Hence, this study aimed at determining the management of non-specific TSP among physiotherapists in Italy. Methods: A web cross-sectional survey investigating physiotherapists' management of non-specific TSP was conducted. The survey instrument was divided into three sections. The first section obtained participants' characteristics. The second section determined participants' agreement with 29 statements regarding the clinical management of non-specific TSP utilising a five-point Likert scale. Participants who partially or completely agreed (scores 4-5) were considered to agree with the statements. A ≥ 70% of agreement with a statement was considered as consensus according to previous literature. The third section asked the participants to indicate how often they adopted several treatments to manage non-specific TSP with a 5-point scale (always - often - sometimes - rarely - never). The frequencies of answers were calculated, and a visual representation through a bar chart was reported. The online version of the survey instrument was delivered through the newsletter of the Italian Association of Physiotherapists and the postgraduate master's degree in Rheumatic and Musculoskeletal Rehabilitation of the University of Genova (Genova, Italy). Results: In total, 424 physiotherapists (mean age (SD): 35.1 years (10.5); 50% female) completed the survey. In the second section, physiotherapists achieved consensus for 22/29 statements. Those statements addressed the importance of psychosocial factors, exercise, education, and manual therapy techniques in managing non-specific TSP. In the third section, 79.7% of participants indicated they would always adopt a multimodal treatment (education, therapeutic exercise, manual therapy), followed by education and information (72.9%), therapeutic exercise (62.0%), soft tissue manual therapy (27.1%), and manual therapy (16.5%). Conclusions: Study participants considered fundamentally using a multimodal programme based on education, exercise and manual therapy to manage non-specific TSP. This approach aligns with the CPGs for other chronic musculoskeletal pain than non-specific TSP.

Objectives: To characterize a carbapenem-resistant Citrobacter freundii (Cf-Emp) co-producing class A, B and D carbapenemases, resistant to novel β-lactamase inhibitor combinations (BLICs) and cefiderocol. Methods: Carbapenemase production was tested by an immunochromatography assay. Antibiotic susceptibility testing (AST) was performed by broth microdilution. WGS was performed using short- and long-read sequencing. Transfer of carbapenemase-encoding plasmids was assessed by conjugation experiments. Results: Cf-Emp was isolated on selective medium for carbapenem-resistant Enterobacterales from the surveillance rectal swab taken at hospital admission from a patient of Moroccan origin. Cf-Emp produced three different carbapenemases, including KPC-2, OXA-181 and VIM-1, and was resistant to all β-lactams including carbapenems, novel BLICs (ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam) and cefiderocol. MIC of aztreonam/avibactam was 0.25 mg/L. The strain belonged to ST22, one of the C. freundii lineages of global diffusion, known to be associated with carbapenemase production. Each carbapenemase gene was located aboard a different plasmid (named pCf-KPC, pCf-OXA and pCf-VIM, respectively), which also carried other clinically relevant resistance genes, such as armA (pCf-KPC), blaSHV-12 (pCf-VIM) and qnrS1 (pCf-OXA). Transferability to Escherichia coli J53 by conjugation was observed for all plasmids. Conclusions: The finding of enterobacterial strains carrying multiple carbapenemase genes on transferable plasmids is alarming, because similar strains could provide an important reservoir for disseminating these clinically relevant resistance determinants.

Introduction: Therapy of Myasthenia Gravis (MG) is undergoing a profound change with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. Objective of the study was to perform a meta-analysis and network meta-analysis of randomized and placebo-controlled trials of innovative therapies in MG with available efficacy data. Methods: We assessed statistical heterogeneity across trials with Cochrane Q test and I2 values. We pooled mean differences with the random effect model. We derived treatment efficacy after 26 weeks of treatment with Eculizumab and Ravulizumab, 28 days with Efgartigimod, 43 days with Rozanolixizumab, 12 weeks with Zilucoplan, and after 16, 24 or 52 weeks with Rituximab. Results: We observed an overall mean MG-ADL change of -2.17 points (95% CI -2.67, -1.67; p<0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti-FcRns (p=0.16). The QMG change was -3.46 (95%CI -4.53, -2.39; p<0.001), with a higher reduction with FcRns (-4.78 vs -2.60; p<0.001). Rituximab did not significantly improve the MG-ADL (-0.92, CI95% -2.24, 0.39; p=0.17), or QMG (-1.9, 95%CI -3.97, 0.18, p=0.07). At the network meta-analysis, Efgartigimod had the highest probability to be the best treatment, followed by Rozanolixizumab. Interpretation: Anti-complement and FcRn treatments proved to be both effective in MG patients, whereas Rituximab did not show a significant benefit for patients. With the limitations of this meta-analysis, including efficacy time-points, FcRn treatments showed a short-term higher effect on the QMG. Real-life studies with long-term measurements are needed to confirm our results.

Application of chemical bonding analysis in position-space techniques based on combined topological analysis of the electron density and electron-localizability indicator distributions has recently led to the formulation of a polarity-extended 8 - Neff rule for consistent inclusion of quantum chemically obtained polar-covalent bonding data into the classical 8 - N scheme for main-group compounds. Previous application of this scheme to semiconducting main-group compounds of the cubic MgAgAs type of structure with 8 valence electrons per formula unit (8 ve per f.u.) has shown a covalent bonding tendency preferring one zinc blende type partial structure over the other one, which seems to corroborate the classical Lewis picture of maximally four covalent bonds per main-group element. In contrast to the MgAgAs type, the orthorhombic TiNiSi type of structure displays a much higher geometrical flexibility to incorporate different kinds of metal atoms. The analysis of polar-covalent bonding in semiconducting 8 ve per f.u. containing main-group compounds AA'E of this structure type reveals a transition to non-Lewis type bonding scenarios of species E with up to ten polar-covalently bonded metal atoms. This kind of situation is consistently included into the extended 8 - Neff type bonding scheme. A systematic increase of partially covalent bonding from chalcogenides E16 to the tetrelides E14 is found, summing up to as much as 2 covalent bonds E14-A and E14-A', and correspondingly remaining 4 lone pair type electrons on species E14. The familiar notion of this structure type consisting of a '[NiSi]'-type framework with 'Ti'-type atoms filling the voids cannot be supported for the compounds investigated.

A dataset to describe exposed bedrock and surficial geology of Antarctica has been constructed by the GeoMAP Action Group of the Scientific Committee on Antarctic Research (SCAR) and GNS Science. Our group captured existing geological map data into a geographic information system (GIS), refined its spatial reliability, harmonised classification, and improved representation of glacial sequences and geomorphology, thereby creating a comprehensive and coherent representation of Antarctic geology. A total of 99,080 polygons were unified for depicting geology at 1:250,000 scale, but locally there are some areas with higher spatial resolution. Geological unit definition is based on a mixed chronostratigraphic- and lithostratigraphic-based classification. Description of rock and moraine polygons employs the international Geoscience Markup Language (GeoSciML) data protocols to provide attribute-rich and queryable information, including bibliographic links to 589 source maps and scientific literature. GeoMAP is the first detailed geological map dataset covering all of Antarctica. It depicts ‘known geology’ of rock exposures rather than ‘interpreted’ sub-ice features and is suitable for continent-wide perspectives and cross-discipline interrogation.

Due to their unique physicochemical properties, graphene and its derivatives are widely exploited for biomedical applications. It has been shown that graphene may exert different degrees of toxicity in in vivo or in vitro models when administered via different routes and penetrated through physiological barriers, subsequently being distributed within tissues or located within cells. In this study, in vitro neurotoxicity of graphene with different surface areas (150 and 750 m2/g) was examined on dopaminergic neuron model cells. SH-SY5Y cells were treated with graphene possessing two different surface areas (150 and 750 m2/g) in different concentrations between 400 and 3.125 μg/mL, and the cytotoxic and genotoxic effects were investigated. Both sizes of graphene have shown increased cell viability in decreasing concentrations. Cell damage increased with higher surface area. Lactate dehydrogenase (LDH) results have concluded that the viability loss of the cells is not through membrane damage. Neither of the two graphene types showed damage through lipid peroxidation (MDA) oxidative stress pathway. Glutathione (GSH) values increased within the first 24 and 48 h for both types of graphene. This increase suggests that graphene has an antioxidant effect on the SH-SY5Y model neurons. Comet analysis shows that graphene does not show genotoxicity on either surface area. Although there are many studies on graphene and its derivatives on their use with different cells in the literature, there are conflicting results in these studies, and most of the literature is focused on graphene oxide. Among these studies, no study examining the effect of graphene surface areas on the cell was found. Our study contributes to the literature in terms of examining the cytotoxic and genotoxic behavior of graphene with different surface areas.