Mantra 2.0: an online collaborative resource for drug mode of action and repurposing by network analysis.

SUMMARY: Elucidation of molecular targets of a compound [mode of action (MoA)] and its off-targets is a crucial step in drug development. We developed an online collaborative resource (MANTRA 2.0) that supports this process by exploiting similarities between drug-induced transcriptional profiles. Drugs are organized in a network of nodes (drugs) and edges (similarities) highlighting 'communities' of drugs sharing a similar MoA. A user can upload gene expression profiles before and after drug treatment in one or multiple cell types. An automated processing pipeline transforms the gene expression profiles into a unique drug 'node' embedded in the drug-network. Visual inspection of the neighbouring drugs and communities helps in revealing its MoA and to suggest new applications of known drugs (drug repurposing). MANTRA 2.0 allows storing and sharing user-generated network nodes, thus making MANTRA 2.0 a collaborative ever-growing resource. AVAILABILITY AND IMPLEMENTATION: The web tool is freely available for academic use at http://mantra.tigem.it.

Fingerprinting Mediterranean hurricanes using pre-event thermal drops in seawater temperature.

Extreme atmospheric-marine events, known as medicanes (short for "Mediterranean hurricanes"), have affected the Mediterranean basin in recent years, resulting in extensive coastal flooding and storm surges, and have occasionally been responsible for several casualties. Considering that the development mechanism of these events is similar to tropical cyclones, it is plausible that these phenomena are strongly affected by sea surface temperatures (SSTs) during their development period (winter and autumn seasons). In this study, we compared satellite data and the numerical reanalysis of SSTs from 1969 to 2023 with in situ data from dataloggers installed at different depths off the coast of southeastern Sicily as well as from data available on Argo floats on the Mediterranean basin. A spectral analysis was performed using a continuous wavelet transform (CWT) for each SST time series to highlight the changes in SSTs prior to the occurrence of Mediterranean Hurricanes as well as the energy content of the various frequencies of the SST signal. The results revealed that decreases in SST occurred prior to the formation of each Mediterranean hurricane, and that this thermal drop phenomenon was not observed in intense extra-tropical systems. The spectral analyses revealed that high CWT coefficients representing high SST energy contents were observed before the occurrence of a Mediterranean hurricane. This information may provide a useful fingerprint for distinguishing Mediterranean hurricanes from common seasonal storms at the onset of these events.

Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.

UNLABELLED: Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). CONCLUSIONS: In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.

Simulation of a flash-flood event over the Adriatic Sea with a high-resolution atmosphere-ocean-wave coupled system.

On the morning of September 26, 2007, a heavy precipitation event (HPE) affected the Venice lagoon and the neighbouring coastal zone of the Adriatic Sea, with 6-h accumulated rainfall summing up to about 360 mm in the area between the Venetian mainland, Padua and Chioggia. The event was triggered and maintained by the uplift over a convergence line between northeasterly flow from the Alps and southeasterly winds from the Adriatic Sea. Hindcast modelling experiments, using standalone atmospheric models, failed to capture the spatial distribution, maximum intensity and timing of the HPE. Here we analyze the event by means of an atmosphere-wave-ocean coupled numerical approach. The combined use of convection permitting models with grid spacing of 1 km, high-resolution sea surface temperature (SST) fields, and the consistent treatment of marine boundary layer fluxes in all the numerical model components are crucial to provide a realistic simulation of the event. Inaccurate representations of the SST affect the wind magnitude and, through this, the intensity, location and time evolution of the convergence zone, thus affecting the HPE prediction.

Effect of a positive Sea Surface Temperature anomaly on a Mediterranean tornadic supercell.

Extreme events represent a topic of paramount importance and a challenge for modelling investigations. Due to the need of high-resolution models, the study of severe localized convective phenomena is even more critical, especially in relation to changes in forcing factors, such as sea surface temperatures (SSTs), in future climate scenarios. Here, we analyze the effect of changes in SSTs on the intensity of a tornadic supercell in the Mediterranean through modelling investigations. We show dramatic (nonlinear) changes for updraft helicity and vertical velocity, which measure the intensity of the supercell, even for variations of SST only of + /-1 K.