A NUMB–EFA6B–ARF6 recycling route controls apically restricted cell protrusions and mesenchymal motility

International audienceThe endocytic protein NUMB has been implicated in the control of various polarized cellular processes, including the acquisition of mesenchymal migratory traits through molecular mechanisms that have only been partially defined. Here, we report that NUMB is a negative regulator of a specialized set of understudied, apically restricted, actin-based protrusions, the circular dorsal ruffles (CDRs), induced by either PDGF or HGF stimulation. Through its PTB domain, NUMB binds directly to an N-terminal NPLF motif of the ARF6 guanine nucleotide exchange factor, EFA6B, and promotes its exchange activity in vitro. In cells, a NUMB-EFA6B-ARF6 axis regulates the recycling of the actin regulatory cargo RAC1 and is critical for the formation of CDRs that mark the acquisition of a mesenchymal mode of motility. Consistently, loss of NUMB promotes HGF-induced cell migration and invasion. Thus, NUMB negatively controls membrane protrusions and the acquisition of mesenchymal migratory traits by modulating EFA6B-ARF6 activity

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Oltre la linea (collana di Bonanno Editore)

La collana scientifica "Oltre la linea", promossa da Bonanno Editore (Acireale - Roma), intende offrire argomenti sociologici in un'ottica particolare, lontana da schematismi e strutturalismi, aperta invece a contributi "eterodossi", comprensivi di innovativi sguardi verso le arti figurative

Il terzo settore attraverso le parole degli intervistati

Che cosa resta quando la crisi economica erode la coesione sociale, quando messaggi razzisti coprono il vuoto politico, quando l’individualismo rompe i legami collettivi? Che cosa succede nel momento in cui l’elenco dei diritti “di nuova generazione” si allunga sempre di più e la loro efficacia progressivamente svanisce? Che cosa accade quando la “società del welfare” diventa un ricordo in bianco e nero? Trionferà il mercato come dimensione unificante? Un variegato mondo associativo, solidale e no profit non si arrende, muovendosi ostinatamente in direzione contraria. Associazioni, Ong, forum sociali e reti di volontariato costituiscono una realtà affascinante, a volte vischiosa, comunque mai banale. Questo libro ne disegna i contorni: che cosa è, per quali obiettivi lotta e quali risultati ha ottenuto la solidarietà in Italia

Subcochlear canaliculus patterns in the pediatric and adult population: radiological findings and surgical implications

The pneumatization of the different regions of the temporal bone is strictly related to the age and the degree of development of the mastoid and the middle ear. Petrous apex pneumatization is the last step of the development of the petrous bone system. The subcochlear canaliculus is an anatomical cavity, originating in the space between the fustis and the finiculus, and connecting the round window area to the petrous apex. The aim of the present article is analyzing the trend of development of the subcochlear canaliculus pneumatization, classified through CT scan examination, in different age subgroups

Artificial intelligence in head and neck cancer diagnosis

Introduction: Artificial intelligence (AI) is currently being used to augment histopathological diagnostics in pathology. This systematic review aims to evaluate the evolution of these AI-based diagnostic techniques for diagnosing head and neck neoplasms. Materials and methods: Articles regarding the use of AI for head and neck pathology published from 1982 until March 2022 were evaluated based on a search strategy determined by a multidisciplinary team of pathologists and otolaryngologists. Data from eligible articles were summarized according to author, year of publication, country, study population, tumor details, study results, and limitations. Results: Thirteen articles were included according to inclusion criteria. The selected studies were published between 2012 and March 1, 2022. Most of these studies concern the diagnosis of oral cancer; in particular, 6 are related to the oral cavity, 2 to the larynx, 1 to the salivary glands, and 4 to head and neck squamous cell carcinoma not otherwise specified (NOS). As for the type of diagnostics considered, 12 concerned histopathology and 1 cytology. Discussion: Starting from the pathological examination, artificial intelligence tools are an excellent solution for implementing diagnosis capability. Nevertheless, today the unavailability of large training datasets is a main issue that needs to be overcome to realize the true potential