Knowledge on multiple interdependences between quality of life (QoL) and behavioural problems in relation to asthma severity and control is undetermined. The aims of the study were: (i) to assess the ...relationship of QoL and behavioural problems with asthma severity and control (ii) to predict children's "abnormal/borderline" status with variation in QoL. For these purposes a multicenter case-control study on 47 Severe Asthma (SA) and 94 Moderate Asthma (MA) children was performed. The MIMIC approach was applied to investigate the effect of SA and non-controlled asthma (NC) on QoL and behavioural disorders. Logistic regression was used to estimate probabilities of having an "abnormal/borderline" status with variation in QoL. The MIMIC model showed that the magnitude of the effect of SA and NC was larger on QoL (β = -0.37 and β = -0.30, respectively) than on behavioural problems (β = 0.27). With regards to the probability of having a borderline status, in MA a QoL of 1 returned a probability of 0.81, whereas in SA a QoL of 1 returned a probability of 0.89. In conclusion, SA children are highly affected by impaired QoL and behavioural problems. The MIMIC model allowed us to obtain a comprehensive assessment of QoL and behavioural problems with asthma severity and control.
We describe a sequence-based computational model to predict DNA G-quadruplex (G4) formation. The model was developed using large-scale machine learning from an extensive experimental G4-formation ...dataset, recently obtained for the human genome via G4-seq methodology. Our model differentiates many widely accepted putative quadruplex sequences that do not actually form stable genomic G4 structures, correctly assessing the G4 folding potential of over 700,000 such sequences in the human genome. Moreover, our approach reveals the relative importance of sequence-based features coming from both within the G4 motifs and their flanking regions. The developed model can be applied to any DNA sequence or genome to characterise sequence-driven intramolecular G4 formation propensities.
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising ...prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).
Asthma is a common disease in childhood with a minority of affected children suffering from severe asthma. Patients with severe asthma require high dose inhaled glucocorticoids plus a second ...controller and/or systemic corticosteroids to be well‐controlled or remain uncontrolled despite such treatment. Although only a small subset of children and adolescents falls in this category, the management of affected patients represents a major concern for pediatricians. Guidelines and recommendations have been designed to guide the management of this group of patients. Though the terms “recommendations” and “guidelines” are often used interchangeably, it should be noted that the first one should be used more narrowly to identify specific actions and the second one to broadly refer to the umbrella under which multiple recommendations for a specific condition are provided. Moreover, the availability of several and sometimes‐conflicting documents on severe asthma management both in adult and pediatric age could generate confusion among health care professionals. The manuscript analyses seven papers addressing severe asthma, comparing any key aspects and differences. Finally, we tried to create a more practical document for physicians to simplify the interpretation of the several available documents on severe asthma management focusing the pediatric age.
The use of a caged G-quadruplex ligand allows for transcriptional control of quadruplex-containing genes using UV light as an external trigger. An important oncogene, SRC, involved in the initiation ...and proliferation of epithelial tumours is shown to be significantly downregulated in cells treated by the caged ligand in synergy with UV light treatment.
Self-assembled helical polymers hold great promise as new functional materials, where helical handedness controls useful properties such as circularly polarized light emission or electron spin. The ...technique of subcomponent self-assembly can generate helical polymers from readily prepared monomers. Here we present three distinct strategies for chiral induction in double-helical metallopolymers prepared via subcomponent self-assembly: (1) employing an enantiopure monomer, (2) polymerization in a chiral solvent, (3) using an enantiopure initiating group. Kinetic and thermodynamic models were developed to describe the polymer growth mechanisms and quantify the strength of chiral induction, respectively. We found the degree of chiral induction to vary as a function of polymer length. Ordered, rod-like aggregates more than 70 nm long were also observed in the solid state. Our findings provide a basis to choose the most suitable method of chiral induction based on length, regiochemical, and stereochemical requirements, allowing stereochemical control to be established in easily accessible ways.
ACI for Safety and Sustainability in Motorsport Balestrieri, Stefania; Daidone, Lauragrazia; Giovanni, Marco Antonio Di ...
Transportation research procedia (Online),
2023, 2023-00-00, Letnik:
69
Journal Article
Odprti dostop
ACI has always supported the sustainable planning and management of sporting events, based on the principles of a Corporate Social Responsibility which increasingly combines environmental, ethical ...and social values, and promotes new lifestyles. In this context, ACI has recently launched an Environmental Certification programme for the most relevant motor sport events at a national level. The goal of the program is to increase the awareness about environmental management issues in order to reduce the sport competitions footprint.
The Environmental Certification is the company's commitment to social responsibility to reduce the impact of its activities in compliance with the applicable environmental regulations. This programme includes a multi-step process that starts with the assessment of the current sustainability level of an event and its relevant rating. It then defines a roadmap of potential actions to be implemented to achieve higher levels of accreditation up to the excellence.
The accreditation process is based on a three-star rating system, from 1-star “Committed to excellence” to 3-star “Achieving Excellence”.
Designed by the Technical Department of the Automobile Club of Italy, the project specifically aims to evaluate the sustainability performance - not only in terms of CO2 produced - of all the activities linked to an event. It also aims to develop a best practice framework and to accredit those stakeholders who adopt it to achieve carbon offsetting and neutrality.
The environmental certification complies with the standards and the methodology of the Environmental Accreditation Programme developed by the FIA for the World Motor Racing competitions. The environmental parameters used in the checklists for the quantitative and qualitative assessments are based on the standards set by the international regulations on the certification of sustainable event management systems (ISO).
Osteosarcomas (OTS) represent the most common primary bone cancer diagnosed in adolescents and young adults. Despite remarkable advances, there are no objective molecular or imaging markers able to ...predict an OTS outcome at diagnosis. Focusing on biomarkers contributing broadly to treatment resistance, we examine the interplay between the tumor-associated macrophages and intra-tumor hypoxia.
Radiological and immunohistochemical (IHC) data were correlated with the outcome in a retrospective and monocentric cohort of 30 pediatric OTS. We studied hypoxic (pS6, phospho-mTor, HIF-1α and carbonic anhydrase IX (CAIX)) and macrophagic (CD68 and CD163) biomarkers.
The imaging analyses were based on MRI manual volumetric measures on axial post-contrast T1 weighted images, where, for each tumor, we determined the necrotic volume and its ratio to the entire tumor volume. When they were above 50 cm
and 20%, respectively, they correlated with a worse overall survival (
= 0.0072 and
= 0.0136, respectively) and event-free survival (
= 0.0059 and
= 0.0143, respectively). IHC assessments enable a significant statistical link between HIF-1α/CAIX hyper-expressions, CD68+ cells and a worse outcome, whereas activation of mTor pathway was linked to a better survival rate and CD163+ cells.
This study evidenced the links between hypoxia and immunity in OTS, as their poor outcome may be related to a larger necrotic volume on diagnostic MRI and, in biopsies, to a specific IHC profile.
This research takes into account recent reforms concerning the sporting organisations and examines their internal democratic structure. In the first place, it addresses the international convergences ...on the elections of the governing bodies, analysing the issue of the eligibility criteria and the fundamental elements of the internal control system. Secondly, it examines the coherence of the ‘external’ control of the sporting organisations with the principle of the autonomy of sport, investigating the implications of the general principle of cooperation and transparency. The study illustrates what idea of democracy is emerging from the metamorphosis of sporting organisations at national and international level, introducing some interpretations of the juridical nature of the sport legal order.
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