General Ramified Recurrence is Sound for Polynomial Time

Leivant's ramified recurrence is one of the earliest examples of an implicit characterization of the polytime functions as a subalgebra of the primitive recursive functions. Leivant's result, however, is originally stated and proved only for word algebras, i.e. free algebras whose constructors take at most one argument. This paper presents an extension of these results to ramified functions on any free algebras, provided the underlying terms are represented as graphs rather than trees, so that sharing of identical subterms can be exploited

From 2-sequents and Linear Nested Sequents to Natural Deduction for Normal Modal Logics

We extend to natural deduction the approach of Linear Nested Sequents and 2-sequents. Formulas are decorated with a spatial coordinate, which allows a formulation of formal systems in the original spirit of natural deduction---only one introduction and one elimination rule per connective, no additional (structural) rule, no explicit reference to the accessibility relation of the intended Kripke models. We give systems for the normal modal logics from K to S4. For the intuitionistic versions of the systems, we define proof reduction, and prove proof normalisation, thus obtaining a syntactical proof of consistency. For logics K and K4 we use existence predicates (following Scott) for formulating sound deduction rules

Training verbal working memory in children with mild intellectual disabilities: effects on problem-solving

This multiple case study explores the effects of a cognitive training program in children with mild to borderline intellectual disability. Experimental training effects were evaluated comparing pre-post-test changes after (a) a baseline phase versus a training phase in the same participant, (b) an experimental training versus either a no intervention phase or a control training in two pairs of children matched for cognitive profile. Key elements of the training program included (1) exercises and card games targeting inhibition, switching, and verbal working memory, (2) guided practice emphasizing concrete strategies to engage in exercises, and (3) a variable amount of adult support. The results show that both verbal working memory analyzed with the listening span test and problem-solving tested with the Raven’s matrices were significantly enhanced after the experimental trainin

Coronavirus disease 2019 (COVID-19) vaccination in patients with cirrhosis: Does it work?

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Nutritional Quality of Wholegrain Cereal-Based Products Sold on the Italian Market: Data from the FLIP Study

The consumption of wholegrains (WG) is encouraged worldwide, but the lack of a common legal definition of such products leads to an unclear classification and identification on the grocery store shelf. In Italy, several products are generally sold as WG, but it cannot be determined if they are made entirely with all WG cereal(s) or if they are partially produced with WG ingredients (PWG). The aims of this study were to (a) survey the number of cereal-based food items formulated with WG, PWG, or refined (RG) present on the Italian market; and (b) analyse the nutritional quality, intended as nutrition facts, of WG products in comparison to PWG and RG. Nutritional information and declarations were retrieved from packs of 3040 products belonging to five different categories: breakfast cereals, biscuits, sweet snacks, bread, and bread substitutes. A descriptive analysis of the products and comparison of energy, macronutrients, fibre and salt among RG, PWG and WG products within each category was performed. In all categories, a major portion of the products did not contain WG ingredients. Results showed that the nutritional quality of RG, PWG, and WG products varied in relation to the product category and that WG inclusion cannot be always considered a marker of the overall nutritional quality of foods. Instead, it is necessary to evaluate the global product characteristics, and it is important to pay attention to differences between WG and PWG products that can be perceived by consumers as equivalent

Yamanaka Factors in the Budding Tunicate Botryllus schlosseri Show a Shared Spatio-Temporal Expression Pattern in Chordates

In vertebrates, the four transcription factors Sox2, c-Myc, Pou5f1 and Klf4 are involved in the differentiation of several tissues during vertebrate embryogenesis; moreover, they are normally co-expressed in embryonic stem cells and play roles in pluripotency, self-renewal, and maintenance of the undifferentiated state in adult cells. The in vitro forced co-expression of these factors, named Yamanaka factors (YFs), induces pluripotency in human or mouse fibroblasts. Botryllus schlosseri is a colonial tunicate undergoing continuous stem cell-mediated asexual development, providing a valuable model system for the study of pluripotency in the closest living relatives of vertebrates. In this study, we identified B. schlosseri orthologs of human Sox2 and c-Myc genes, as well as the closest homologs of the vertebrate-specific Pou5f1 gene, through an in-depth evolutionary analysis of the YF gene families in tunicates and other deuterostomes. Then, we studied the expression of these genes during the asexual cycle of B. schlosseri using in situ hybridization in order to investigate their possible involvement in tissue differentiation and in pluripotency maintenance. Our results show a shared spatio-temporal expression pattern consistent with the reported functions of these genes in invertebrate and vertebrate embryogenesis. Moreover, Myc, SoxB1 and Pou3 were expressed in candidate stem cells residing in their niches, while Pou2 was found expressed exclusively in the immature previtellogenic oocytes, both in gonads and circulating in the colonial vascular system. Our data suggest that Myc, SoxB1 and Pou3 may be individually involved in the differentiation of the same territories seen in other chordates, and that, together, they may play a role in stemness even in this colonial ascidian

In vitro bioaccessibility of phenolic acids from a commercial aleurone-enriched bread compared to a whole grain bread

Wheat aleurone, due to its potentially higher bioaccessibility and bioavailability of micronutrients and phenolic acids, could represent a useful ingredient in the production of commonly consumed cereal-based food. The aim of the present study was to investigate the in vitro bioaccessibility of phenolic acids both from an aleurone-enriched bread and from a whole grain bread. The two bread samples were firstly characterized for the phenolic acid content. An in vitro digestion was then performed in order to evaluate the release of phenolic acids. The results obtained suggest that the bioaccessibility of the phenolic acids in the aleurone-enriched bread is higher than in the whole grain bread. These in vitro results suggest the potential use of aleurone in the production of foods, and this may represent an attractive possibility to vehicle nutritionally interesting components to consumers

TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis

Objectives The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. Methods We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. Results We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. Conclusions Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity