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Rosellina Margherita Mancina,1,* Flaminia Ferri,2,* Alessio Farcomeni,3 Antonio Molinaro,1 Angela Maffongelli,4 Monica Mischitelli,2 Edoardo Poli,2 Lucia Parlati,5 Maria Antonella Burza,6 Adriano De Santis,2 Fabio Attilia,2 Claudia Rotondo,2 Maria Margherita Rando,2 Maria Luisa Attilia,2 Mauro Ceccanti,2 Stefano Ginanni Corradini2 1Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at the University of Gothenburg, Wallenberg Laboratory, Göteborg, Sweden; 2Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; 3Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; 4Department of General Surgery, Urgency and Organ Transplantation, University Hospital “Paolo Giaccone”, University of Palermo, Palermo, Italy; 5Hepatology Department, Université Paris Descartes, Cochin Hospital, APHP, Paris, France; 6Department of Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden *These authors contributed equally to this work Background: Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption.Materials and methods: A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves.Results: We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity.Conclusion: We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors. Keywords: alcoholic cirrhosis, PNPLA3, CD14, predictive score

Adjuvant radiotherapy (RT) plays an essential role in the management of early breast cancer (BC) but can lead to cardiovascular and lung toxicities. Recently, RT strategies have been developed to optimize the dose distribution to reduce the risk of treatment-related morbidities. Deep inspiration breath-hold (DIBH) increases the distance between the heart and chest wall, minimizing the radiation dose to intrathoracic organs at risk without compromising target coverage or increasing low dose scatter. This prospective study (SAVE-HEART; German Clinical Trials Register number: DRKS00011213), aimed to compare surface-guided DIBH to free-breathing (FB) in patients with left-sided BC, by evaluating individual cardiovascular risks and treatment plan dosimetry. The study enrolled 585 patients from October 2016 to January 2021 who met the inclusion criteria of having left-sided invasive breast carcinoma or carcinoma in situ after breast conserving surgery or mastectomy and requiring adjuvant RT of the breast/thoracic wall with or without regional lymph nodes. The ability to hold breath for 20 seconds was also a prerequisite. The treatments were either hypofractionated (HF, 40.05 Gy in 15 fractions) or normofractionated (NF, 50.00 Gy in 25 fractions). DIBH was applied using the automatically triggered surface guidance system CatalystTM (C-RAD, Uppsala, Sweden) with audio and video feedback to the patient. CT and surface data were acquired during both DIBH and free-breathing states. The primary endpoint of the study is the comparative evaluation of heart dose reduction by using DIBH. Treatment plan dosimetry was significantly improved with the use of deep inspiration breath-hold compared to free-breathing in both hypofractionated (HF) and normofractionated (NF) regimens. The mean and maximum doses to the heart and the near maximum dose of the left coronary artery (LAD) were significantly reduced by 36-42% in HF and NF plans (P <0.001), while the mean ipsilateral lung dose was reduced by 12-14% (P <0.001). Furthermore, the use of DIBH resulted in a 5% reduction in the cumulative 10-year cardiovascular disease risk (10y-CVD risk) compared to radiotherapy without DIBH (3.59% to 3.41%; P <0.001). To the best of our knowledge, this is the largest prospective study to demonstrate a significant advantage in treatment plan dosimetry for the cardiac and ipsilateral lung dose with surface-guided DIBH compared to FB in patients with left-sided BC. [ABSTRACT FROM AUTHOR]

Objectives: To assess treatment satisfaction and owner preference for two delivery devices (VetPen, MSD Animal Health, and U40 insulin syringes) and the effect on glycaemic control in diabetic dogs treated with porcine insulin zinc suspension. Materials and Methods: Randomised prospective cross‐over study with two arms, each of 8 weeks. Twenty client‐owned diabetic dogs on insulin treatment by U40 syringe were enrolled. Dogs were randomly assigned to receive insulin by syringe or pen injector for 2 months, followed by 2 months of the other injection method. Treatment satisfaction and owners' insulin delivery device preference were assessed using a questionnaire. Glycaemic control was assessed using a clinical score, serum fructosamine and glycated haemoglobin (HbA1c%) at the time of the enrolment (T0) and the end of each arm of treatment (T2 and T4). Results: Treatment satisfaction differed for the two types of the delivery device when the order that each device was used was taken into consideration. Owners who used the syringe first did not have a significant preference for an injection device. In contrast, owners who used the pen injector first expressed a significant preference for VetPen compared to syringes. No significant differences in the number of dogs of Groups 1 and 2 with good and poor glycaemic control at T2 and T4 were detected. Clinical Significance: Overall treatment satisfaction and preference for the two delivery methods were similar. However, VetPen was preferred by owners who were randomised to use this device first. Glycaemic control did not appear to be affected by the insulin delivery device used. [ABSTRACT FROM AUTHOR]

During the extended activity of Mount Etna volcano in February–April 2021, three distinct paroxysmal events took place from February 21 to 26, which were associated with a very uncommon transport of the injected upper‐tropospheric plumes toward the north. Using a synergy of observations and modeling, we characterized the emissions and three‐dimensional dispersion for these three plumes, monitored their downwind distribution and optical properties, and estimated their radiative impacts at selected locations. With a satellite‐based source inversion, we estimate the emitted sulfur dioxide (SO2) mass at an integrated value of 55 kt and plumes injections at up to 12 km altitudes, which qualifies this series as an extreme event for Mount Etna. Then, we combine Lagrangian dispersion modeling, initialized with measured temporally resolved SO2 emission fluxes and altitudes, with satellite observations to track the dispersion of the three individual plumes. The transport toward the north allowed the height‐resolved downwind monitoring of the plumes at selected observatories in France, Italy, and Israel, using LiDARs and photometric aerosol observations. Volcanic‐specific aerosol optical depths (AODs) in the visible spectral range ranging from about 0.004 to 0.03 and local daily average shortwave radiative forcing (RF) ranging from about −0.2 to −1.2 W m−2 (at the top of atmosphere) and from about −0.2 to −3.0 W m−2 (at the surface) are found. The composition (possible presence of ash), AOD, and RF of the plume have a large inter‐plume and intra‐plume variability and thus depend strongly on the position of the sampled section of the plumes. Plain Language Summary: The volcanic plumes from Mount Etna's eruptions disperse usually toward the east, to the Central‐Eastern Mediterranean, where ground stations are not available to monitor and characterize them. During the extended intense volcanic activity of Mount Etna in February–April 2021, some of the plumes dispersed toward the north, in an area where many and well‐equipped ground observatories are available. This was a unique opportunity to study the emissions, dispersion dynamics, shape/composition, and impacts of Mount Etna's aerosol plumes. We analyzed these rare events using many information layers: satellite observations, numerical simulation of the plume's dispersion, and downwind ground‐based observatories. By coupling these information pieces, we could reconstruct these events and untangle their impacts from those of a major Saharan dust outbreak that occurred simultaneously. These events were found quite extreme for Mount Etna (extreme emissions and high altitude—around 12 km). We found that this type of extreme Etna's eruptions has a relevant (and not yet studied) impact on the atmospheric composition and regional climate in the Mediterranean area. The plumes, after continental dispersion, exhibit a complex filamentary shape and a complex aerosol composition and properties, due to the presence of both sulfur‐containing particles and ash. Key Points: Three distinct paroxysmal events took place at Mount Etna from February 21 to 26, 2021 and the plumes were transported toward the northPlumes dispersion is characterized with Lagrangian modeling initialized with measured SO2 emissions and with satellite observationsA series of LiDARs detected and characterized the plumes downwind and their observations are used to estimate the plumes radiative forcing [ABSTRACT FROM AUTHOR]