Ferroportin inhibitor vamifeport ameliorates ineffective erythropoiesis in a mouse model of β-thalassemia with blood transfusions

β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent b-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was previously shown to ameliorate anemia, ineffective erythropoiesis, and dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia, under non-transfused conditions. Our study aimed to assess the effects of oral vamifeport on iron-related parameters (including plasma NTBI levels) and ineffective erythropoiesis following blood transfusions in Hbbth3/+ mice. A single dose of vamifeport prevented the transient transfusion-mediated NTBI increase in Hbbth3/+ mice. Compared with vehicle treatment, vamifeport significantly increased hemoglobin levels and red blood cell counts in transfused mice. Vamifeport treatment also significantly improved ineffective erythropoiesis in the spleens of Hbbth3/+ mice, with additive effects observed when treatment was combined with repeated transfusions. Vamifeport corrected leukocyte counts and significantly improved iron-related parameters (serum transferrin, TSAT and erythropoietin levels) versus vehicle treatment in Hbbth3/+ mice, irrespective of transfusion status. In summary, vamifeport prevented transfusion-mediated NTBI formation in Hbbth3/+ mice. When given alone or combined with blood transfusions, vamifeport also ameliorated anemia, ineffective erythropoiesis, and dysregulated iron homeostasis. Administering vamifeport together with repeated blood transfusions additively ameliorated anemia and ineffective erythropoiesis in this mouse model, providing preclinical proof-of-concept for the efficacy of combining vamifeport with blood transfusions in β-thalassemia

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Cartographie des ressources de l'italianisme

Une nouvelle ressource est disponible sur FGBlog! Fonte Gaia recense pour vous tous les lieux de l'italianisme en France. Cette carte interactive indique la localisation des différentes structures qui proposent des ressources précieuses pour l'italianisme: laboratoires, bibliothèques... Vous y trouverez également les partenaires du projet Fonte Gaia. Cette carte restera disponible sur FGBlog de manière permanente. Pour la retrouvez par la suite, il vous suffira de cliquer sur l'onglet Ressour..

Cartographie des ressources de l'italianisme

Une nouvelle ressource est disponible sur FGBlog! Fonte Gaia recense pour vous tous les lieux de l'italianisme en France. Cette carte interactive indique la localisation des différentes structures qui proposent des ressources précieuses pour l'italianisme: laboratoires, bibliothèques... Vous y trouverez également les partenaires du projet Fonte Gaia. Cette carte restera disponible sur FGBlog de manière permanente. Pour la retrouvez par la suite, il vous suffira de cliquer sur l'onglet Ressour..

Anna Ingoglia

Étudiante en fin de master "métiers des bibliothèques" à l'UPMF, je travaille au SID2 Grenoble, et plus précisément au Cadist d'italien. Dans ce contexte, je participe au développement de FGBlog. Je suis intéressée par les enjeux contemporains de la bibliothèque: open access, numérisation du patrimoine écrit et projets de collaboration avec la recherche universitaire... Ces thématiques qui sont au cœur de Fonte Gaia rendent ce projet particulièrement motivant et ouvrent de nombreuses perspect..

Le Laboratoire italien bascule sur Revue.org

La revue Laboratoire italien publiée par ENS Édition (soutien de l’UMR 5206 Triangle et du Dipartimento di scienze giuridiche de l’Université de Trente) amorce une grande transition de l'imprimé vers le tout électronique. Le n°15 (Venise XXe siècle) constitue le dernier numéro imprimé tandis que le n°16 à venir sera publié sous un format exclusivement électronique. C'est le portail Revues.org qui a été choisi pour la diffusion de la version électronique. Bonne nouvelle : ce portail développ..

Bibliothèques et société

Si le rôle social des bibliothèques n\u27est plus à prouver, on constate que l\u27innovation peut naître des différentes manières dont la bibliothèque se positionne par rapport à la société

Bibliothèques et société

Si le rôle social des bibliothèques n\u27est plus à prouver, on constate que l\u27innovation peut naître des différentes manières dont la bibliothèque se positionne par rapport à la société

Il matrimonio religioso oggi: le nuove sfide della secolarizzazione

In many countries, including Italy, the law of marriage has now been divorced from its Judeo-Christian heritage and given a secular meaning. Can marriage itself survive this process of secularization? The volume explores the drift away from marriage as the basis for family formation in Italy and Europe, and the weakening of the marriage contract in law

Citations and metrics of journals\ua0discontinued from Scopus for publication concerns: the GhoS(t)copus Project

Background: Scopus is a leading bibliometric database. It contains a large part of the articles cited in peer-reviewed publications . The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for 'publication concerns'. Previously published articles may remain indexed and can be cited. Their metrics have yet to be studied. This study aimed to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals. Methods: We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns. Results: A total of 317 journals were evaluated. Ninety-three percent of the journals (294/317) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals were Medicine (52/317; 16%), Agriculture and Biological Science (34/317; 11%), and Pharmacology, Toxicology and Pharmaceutics (31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 16.89 citations, p<0.0001), and so was the number of citations per document (median of difference 0.42 citations, p<0.0001). Twenty-two percent (72/317) were included in the Cabell's blacklist. The DOAJ currently included only 9 journals while 61 were previously included and discontinued, most for 'suspected editorial misconduct by the publisher'. Conclusions: Journals discontinued for 'publication concerns' continue to be cited despite discontinuation and predatory behaviour seemed common. These citations may influence scholars' metrics prompting artificial career advancements, bonus systems and promotion. Countermeasures should be taken urgently to ensure the reliability of Scopus metrics for the purpose of scientific assessment of scholarly publishing at both journal- and author-level