Pegylated-liposomes increase the efficacy of Idelalisib in lymphoma B-cells

New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids. The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug

Qu’est-ce qu’un « Livre des Morts » ? Origine et évolution d’un recueil de textes funéraires

Il Libro dei Morti ha avuto una lunga genesi, basata in parte su testi più antichi facenti parte di due altri corpora: Testi delle Piramidi e Testi dei Sarcofagi. A partire soprattutto dalla XVIII dinastia, il Libro dei Morti iniziò a diffondersi in tutto l'Egitto, a partire dall'area tebana. Dopo secoli di utilizzo, questa composizione fu sottoposta a un processo di revisione che portò a una sua "uniformazione" il cui prodotto è noto come "recensione saita". Il Libro dei Morti è attestato siano all'Epoca Romana.The Book of the Dead had a long genesis, based in part on older texts that were part of two other corpora: The Pyramid Texts and The Coffin Texts. Starting mainly in the 18th dynasty, the Book of the Dead began to spread throughout Egypt, beginning in the Theban area. After centuries of use, this composition underwent a revision process that led to its ‘standardisation’, the product of which is known as the ‘Saite recension’. The Book of the Dead is attested as far back as the Roman era

Metaphors We Live By. Pour une approche comparative (français et italien) et épistémique du métalangage de la sémantique cognitive

The reconstruction of a «genesis of linguistic concepts» falls under the dialectic process implying terminology and the categorial procedures of the 'fabrication' of the scientific objects (Lavieri 2007). How does linguistics think of its translatability? How does the linguistic knowledge (re)organize itself in the translation process? From this perspective, it seems us necessary analyzing the appropriation and utilization forms of the keywords such as «mapping» and «frame» in the French and Italian translations of the text Metaphors We Live By (Lakoff and Johnson 1980). This study aims to show the methodological processes adopted by cognitive linguistics in a comparative and epistemological space.La reconstruction d’une « genèse des concepts linguistiques » s’inscrit dans un processus dialectique impliquant la terminologie et les procédures catégorielles de 'fabrication' des objets scientifiques (Lavieri 2007). De quelle façon la linguistique pense sa propre traduisibilité ? Comment se (ré)organisent les savoirs linguistiques dans le processus traductif ? Dans cette perspective, il nous semble nécessaire d’analyser les formes d’appropriation et d’utilisation de quelques mots-clés comme, par exemple, « mapping » et « frame » dans les traduction française et italienne du texte Metaphors We Live By (Lakoff et Johnson 1980). Cette étude vise donc à réfléchir sur les procédés méthodologiques adoptés par la linguistique cognitive dans un espace comparatif et épistémologique

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 21% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 130 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (188%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (502%) of 11 476 included individuals were female and 5720 (498%) were male. Sex data were missing for 372 (31%) of 11 848 individuals. Median age at registry entry was 96 years (IQR 58-132). 10 099 (899%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (101%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (52%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [924%] of 10 202) than in children and adolescents from non-high-income countries (199 [480%] of 415). 3414 (316%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (724%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 500 mmol/L (IQR 405-608). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation.Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

DIFFERENT METHODOLOGIES FOR EVALUATING THE EQUIVALENT DAMPING RATIO DUE TO CROSS LAMINATED TIMBER ROOF STRUCTURE IN SEISMIC RESTORATION OF AN HISTORICAL CHURCH

The paper shows different methods to evaluate the Equivalent Damping Ratio for historical church reinforced by cross laminated timber roof structure. The role of roof in the seismic restoration of historical churches, characterized by one nave configuration and masonry walls, is crucial in order to avoid the out-of-plane rocking mechanisms of the lateral walls and reduce the in-plane shear forces stressing the façade. Wooden based roof structures are preferable for this kind of constructions because they respect the conservation requirements, being compatible to the original materials. Therefore, the roof should be able to dissipate the seismic inertia forces in the nave transversal response, working as a dissipative diaphragm. Some solutions for the roof-diaphragm are here discussed and the relative Equivalent Damping Ratio is evaluated for a case study modelled with finite elements. Equivalent damping ratio is initially estimated by nonlinear static analyses (pushover analyses) based on the Coefficient Method and the Capacity Spectrum Method. Moreover, the equivalent damping ratio is determined also by nonlinear dynamic analyses where the seismic action is represented by seven spectrum-compatible accelerograms. Finally, the equivalent damping ratio values are compared themselves to optimize the wooden based roof structures in terms of strength and stiffness by showing possible configurations for type of wood (hardwood in double planks or industrial technology as Cross Laminated Timber panels) and steel connections

Addendum to the paper "Refined criteria toward boundedness in an attraction-repulsion chemotaxis system with nonlinear productions"

These notes aim to provide a deeper insight on the specifics of the paper "Refined criteria toward boundedness in an attraction-repulsion chemotaxis system with nonlinear pro ductions" by A. Columbu, S. Frassu and G. Viglialoro

Prediction of severe infections in chronic lymphocytic leukemia: a simple risk score to stratify patients at diagnosis

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients

Citation prediction by leveraging transformers and natural language processing heuristics

In scientific papers, it is common practice to cite other articles to substantiate claims, provide evidence for factual assertions, reference limitations, and research gaps, and fulfill various other purposes. When authors include a citation in a given sentence, there are two considerations they need to take into account: (i) where in the sentence to place the citation and (ii) which citation to choose to support the underlying claim. In this paper, we focus on the first task as it allows multiple potential approaches that rely on the researcher's individual style and the specific norms and conventions of the relevant scientific community. We propose two automatic methodologies that leverage transformers architecture for either solving a Mask-Filling problem or a Named Entity Recognition problem. On top of the results of the proposed methodologies, we apply ad-hoc Natural Language Processing heuristics to further improve their outcome. We also introduce s2orc-9K, an open dataset for fine-tuning models on this task. A formal evaluation demonstrates that the generative approach significantly outperforms five alternative methods when fine-tuned on the novel dataset. Furthermore, this model's results show no statistically significant deviation from the outputs of three senior researchers

Assessing Recharge Sources and Seawater Intrusion in Coastal Groundwater: A Hydrogeological and Multi-Isotopic Approach

One of the crucial challenges of our time is climate change. The consequences of rising sea levels and drought greatly impact water resources, potentially worsening seawater intrusion. Characterizing coastal aquifers is an essential step in devising strategies to address these phenomena. Seawater intrusion poses a critical socio-economic and environmental issue in the coastal plain of Muravera, southeastern Sardinia (Italy). This coastal plain is an important agricultural area in Sardinia, and the health of the crops is compromised by the increasing salinization of shallow groundwater. To enhance our understanding of the hydrogeological conceptual model, which is essential for a sustainable resource management system, hydrogeological investigations were conducted and complemented by the chemical and multi-isotopic analyses of groundwater. The main objectives of this study were to identify groundwater recharge areas, understand salinization mechanisms and trace the evolution of water chemistry. Within this framework, a monthly survey monitoring piezometric level and electrical conductivity was carried out for one year. This survey was integrated with chemical and isotope analyses, including δ18OH2O and δ2HH2O, δ11B, δ18OSO4, δ34SSO4, and 87Sr/86Sr. Hydrochemistry analysis results revealed the occurrence of seawater–freshwater mixing, extending up to 4 km inland. H2O isotope analysis confirmed the mixing processes and indicated the meteoric origin of recharge waters for both shallow and semi-confined aquifers. The strontium isotopes ratio facilitated the identification of four main groundwater flow paths, confirmed by the SIAR model. The results of this combined hydrogeological–geochemical–isotopic survey provide essential elements for the future implementation of an integrated and sustainable management system. These findings enable interventions to slow the process of seawater intrusion and meet the economic needs for the development of local communities