CROSSalive: A web server for predicting the in vivo structure of RNA molecules

Motivation: RNA structure is difficult to predict in vivo due to interactions with enzymes and other molecules. Here we introduce CROSSalive, an algorithm to predict the single-and double-stranded regions of RNAs in vivo using predictions of protein interactions. Results: Trained on icSHAPE data in presence (m6a+) and absence of N6 methyladenosine modification (m6a-), CROSSalive achieves cross-validation accuracies between 0.70 and 0.88 in identifying high-confidence single-and double-stranded regions. The algorithm was applied to the long non-coding RNA Xist (17 900 nt, not present in the training) and shows an Area under the ROC curve of 0.83 in predicting structured regions

New development: Directly elected mayors in Italy: creating a strong leader doesn’t mean creating strong leadership

More than 20 years after their introduction, directly elected mayors are key players in Italian urban governance. This article explains the main effects of this reform on local government systems and provides lessons for other countries considering directly elected mayors

In-hospital and out-of-hospital stroke in patients with COVID-19: two different diseases?

Background: Ischemic stroke is a known complication of COVID-19. It may have a different pathogenesis and worse outcome compared to stroke in patients without COVID-19. Furthermore, patients with COVID-19 and out-of-hospital stroke onset might have different characteristics compared to patients with COVID-19 and in-hospital stroke onset. The aim of our study was to analyze the characteristics of patients with stroke with and without COVID-19 and of patients with COVID-19 with in-hospital and out-of-hospital stroke. Methods: We performed a retrospective study of all consecutive patients admitted to our hospital with ischemic stroke between October 2020 and February 2021. We compared functional outcome, lab test, demographic, and clinical characteristics between patients with or without COVID-19. We performed a sub-analysis comparing patients with COVID-19 and in-hospital and out-of-hospital stroke onset. Results: We included in the final analysis 137 patients of whom 26 with COVID-19. Half (13) had out-of-hospital stroke and half in-hospital stroke onset. Overall, patients with COVID-19 had higher mortality compared to the control group (27% vs 9%, p: 0.02), and non-significantly lower rate of good functional outcome (50% vs 63%, p: 0.22). Patients with COVID-19 and out-of-hospital stroke had higher rate of good functional outcome (69% vs 39%, p: 0.05), higher lymphocyte count, and lower D-dimer compared with patients with in-hospital stroke onset. Conclusions: Patients with stroke and COVID-19 had higher mortality compared to patients without COVID-19. Among patients with COVID-19 those with out-of-hospital stroke had better outcome and fewer blood test abnormalities compared to patients with in-hospital stroke

Attività Fisica Adattata: Taiji-Quan. Una proposta di metodo di lavoro per le persone con Malattia di Parkinson

Riassunto La Malattia di Parkinson è la seconda malattia neurodegenerativa più diffusa al mondo dopo l’Alzheimer. Le persone affette sono ad alto rischio di caduta, con conseguenti disabilità fisiche e psicologiche, con aumento della paura di cadere e di uscire di casa, e riduzione dell’autonomia individuale. I disturbi dell’equilibrio rispondono in maniera incompleta al trattamento farmacologico, mentre si fanno sempre più numerose le evidenze scientifiche che dimostrano come la pratica del Taiji-Quan quale “attività fisica adattata” sia efficace nel migliorare l’equilibrio e dunque la qualità di vita delle persone con Malattia di Parkinson. Il presente lavoro vuole proporre un Programma di Allenamento Adattato di Taiji-Quan, ben definito, ripetibile, completo di significato rieducativo specifico per ogni singolo esercizio, da associare al Programma Farmacologico nel Progetto Riabilitativo Individuale delle persone con Malattia di Parkinson. Tale protocollo è attuabile anche in modalità telematica come tele-riabilitazione

GNAM and OHP: Monitoring Tools for ATLAS experiment at LHC.

ATLAS is one of the four experiments under construction along the Large Hadron Collider (LHC) ring at CERN. The LHC will produce interactions at a center-of-mass energy equal to âs = 14 TeV at 40 MHz rate. The detector consists of more than 140 million electronic channels. The challenging experimental environment and the extreme detector complexity impose the necessity of a common scalable distributed monitoring framework, which can be tuned for the optimal use by different ATLAS sub-detectors at the various levels of the ATLAS data flow. This note presents two monitoring tools that have been developed for this aim within the architecture ATLAS Monitoring Framework and the Data Acquisition System: GNAM and OHP. The first one is a framework for online histogram production; the second one is graphical application for histogram presentation. This tools are now widely used during the ATLAS commissioning and their performances are reported in this not

Middle cerebral artery ischemic stroke and COVID-19: a case report

We present a clinical case of a patient with SARS-CoV-2 infection and respiratory symptoms, complicated with a pro-thrombotic state involving multiple vascular territories and concomitant interleukin-6 increase. This case underlines the possibility to develop a COVID-19-related coagulopathy

Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles

A drawback in the development of treatments that can reach the retina is the presence of barriers in the eye that restrain compounds from reaching the target. Intravitreal injections hold promise for retinal delivery, but the natural defenses in the vitreous can rapidly degrade or eliminate therapeutic molecules. Injectable hydrogel implants, which act as a reservoir, can allow for long-term drug delivery with a single injection into the eye, but still suffer due to the fast clearance of the released drugs when traversing the vitreous and random diffusion that leads to lower pharmaceutic efficacy. A combination with HA-covered nanoparticles, which can be released from the gel and more readily pass through the vitreous to increase the delivery of therapeutic agents to the retina, represents an advanced and elegant way to overcome some of the limitations in eye drug delivery. In this article, we developed hybrid PLGA-Dotap NPs that, due to their hyaluronic acid coating, can improve in vivo distribution throughout the vitreous and delivery to retinal cells. Moreover, a hydrogel implant was developed to act as a depot for the hybrid NPs to better control and slow their release. These results are a first step to improve the treatment of retinal diseases by protecting and transporting the therapeutic treatment across the vitreous and to improve treatment options by creating a depot system for long-term treatments

Tween® preserves enzyme activity and stability in PLGA nanoparticles

Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs

Microfluidic technology for the production of hybrid nanomedicines

Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized

The ROD crate DAQ software framework of the ATLAS data acquisition system

In the ATLAS experiment at the LHC, the ROD Crate DAQ provides a complete software framework to implement data acquisition functionality at the boundary between the detector specific electronics and the common part of the data acquisition system. Based on a plugin mechanism, it allows selecting and using common services (like data output and data monitoring channels) and developing software to control and acquire data from detector specific modules providing the infrastructure for control, monitoring and calibration. Including also event building functionality, the ROD Crate DAQ is intended to be the main data acquisition tool for the first phase of detector commissioning. This paper presents the design, functionality and performance of the ROD Crate DAQ and its usage in the ATLAS data acquisition system and during detector tests