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ABSTRACT Introduction: open tibial fractures are challenging due to the frequent severe bone injury associated with poor soft tissue conditions. This is relevant in low- and middle-income countries, mainly related to delayed definitive fixation and lack of adequate training in soft tissue coverage procedures. Due to these factors, open tibial fracture is an important source of disability for Latin American countries. Herein we sought to provide an epidemiological overview of isolated open tibial shaft fracture across seven hospitals in southern cone of Latin America. The secondary goal was to assess the impact on quality of life based on return-to-work rate (RWR). Methods: patients with an isolated open tibial shaft fracture treated in seven different hospitals from Brazil and Argentina from November 2017 to March 2020 were included in the study. Clinical and radiographic results were evaluated throughout the 120-day follow-up period. Final evaluation compared RWR with the SF-12 questionnaire, bone healing, and gait status. Results: Seventy-two patients were treated, 57 followed for 120 days and 48 completed the SF-12 questionnaire. After 120 days, 70.6% had returned to work, 61.4% had experienced bone healing. Age, antibiotic therapy, type of definitive treatment, and infection significantly influenced the RWR. Gait status exhibited strong correlations with RWR and SF-12 physical component score. Conclusions: Isolated open tibial shaft fractures are potentially harmful to the patient’s quality of life after 120 days of the initial management. RWR is significantly higher for younger patients, no history of infection, and those who could run in the gait status assessment.

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs. 0.69, P

The inhibition of immunosuppressive mechanisms may switch the balance between tolerance and surveillance, leading to an increase in antitumor activity. Regulatory T cells play an important role in the control of immunosuppression, exhibiting the unique property of inhibiting T cell proliferation. These cells migrate to tumor sites or may be generated at the tumor site itself from the conversion of lymphocytes exposed to tumor microenvironment signaling. Because of the high similarity between regulatory T cells and other lymphocytes, the available approaches to inhibit this population are nonspecific and may antagonize antitumor response. In this work we explore a new strategy for inhibition of regulatory T cells based on the use of a chimeric aptamer targeting a marker of immune activation harboring a small antisense RNA molecule for transcriptional gene silencing of Foxp3, which is essential for the control of the immunosuppressive phenotype. The silencing of Foxp3 inhibits the immunosuppressive phenotype of regulatory T cells and potentiates the effect of the GVAX antitumor vaccine in immunocompetent animals challenged with syngeneic tumors. This novel approach highlights an alternative method to antagonize regulatory T cell function to augment antitumor immune responses.

Abstract Glaucoma is a progressive optic neuropathy with characteristic changes to the optic nerve head and the visual field (VF). Detecting progression of VF damage with Standard Automated Perimetry (SAP) is of paramount importance for clinical care. One common approach to detecting progression is to compare each new VF test to a baseline SAP test (event analysis). This comparison is made difficult by the test–retest variability of SAP, which increases with the level of VF damage, and the limited range of measurement, meaning that damage cannot be assessed below a certain level. We performed a prospective international multi-centre data collection of SAP data on 90 eyes from 90 people with glaucoma and different levels of VF damage over a short period of time (6 tests in 60 days). Data were collected using a fundus tracked perimeter (Compass, CenterVue). We used these data (minus the first test) to develop an improved event analysis that accounts for both the change in variability with damage and the lower bound on the measurement imposed by SAP. Using simulations, we show that our approach is more sensitive compared to previously developed methods, especially in the case of advanced glaucoma, while retaining similar specificity.

Abstract Background To investigate whether methotrexate treatment may affect the susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods Clinical assessment of symptoms, SARS-CoV-2 RNA, and anti-SARS-CoV-2 IgG in an initial case series of four families and confirmatory case series of seven families, within which one family member developed coronavirus disease 19 (COVID-19) and exposed another family member receiving methotrexate treatment; experimental part with methotrexate treatment of mice and organoids followed by the assessment of mRNA and protein expression of the SARS-CoV-2 receptor angiotensin-converting enzyme (ACE)-2. Results In the initial case series, three of four women on a joint ski trip developed COVID-19, while the fourth woman, under treatment with methotrexate, remained virus-free. Two of the three diseased women infected their husbands, while the third husband treated with methotrexate remained virus-free. In addition, 7 other families were identified in a follow-up case series, in which one member developed COVID-19, while the other, receiving methotrexate, remained healthy. Experimentally, when mice were treated with methotrexate, ACE2 expression significantly decreased in the lung, in the intestinal epithelium, and in intestinal organoids. Conclusion These clinical and experimental data indicate that methotrexate has certain protective effects on SARS-CoV-2 infection via downregulating ACE2.

The aim of this study (NCT04343053) is to investigate the relationship between platelet activation, myocardial injury, and mortality in patients affected by Coronavirus disease 2019 (COVID-19). Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion [T1], after 7 ± 2 days [T2] and 14 ± 2 days [T3]). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). In COVID-19 patients, P-selectin and sCD40L levels decreased from T1 to T3 and were higher in cases requiring admission to intensive care unit (p = .004 and p = .008, respectively). Patients with myocardial injury (37%), as well as those who died (30%), had higher values of all biomarkers of platelet activation (p

Abstract Background Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Methods Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Results Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). Conclusion In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Objective: To verify if there is a type of image that guides the surgeon in recommending surgical treatment for ankle fractures and assess whether this decision is associated with the evaluator’s age and experience, considering surgeons of different nationalities. Methods: We analyzed 3 different presentations of radiographic images of ankle fractures in 36 patients: anteroposterior and lateral views, true anteroposterior and lateral views, as well as the 3 grouped images. Images were assessed randomly and independently by 89 professionals of different nationalities, ages, and experience. Results: Among professionals from Ecuador, Argentina, Mexico, and Chile, surgery recommendations were more frequent when images were presented in true anteroposterior and lateral views. For professionals from Peru, Venezuela, Bolivia, Paraguay, Brazil, Colombia, Uruguay, and Guatemala, as well as globally, recommendations for surgery were more frequent when grouped images of the 3 positions were presented. In all countries and globally, we verified lower frequencies of surgery recommendations when presenting only anteroposterior and lateral views. Conclusion: In most countries, surgery recommendations were more frequent when grouped images of all 3 views were presented. On the other hand, the highest frequencies of surgery recommendations were observed when images were presented only in true anteroposterior and lateral views. Surgery recommendations were not associated with the experience (years since graduation) of the evaluating physician. Level of Evidence IV; Prognostic Studies; Case Series.

We examine the geometry of the level sets of particular horizontally p-harmonic functions in the Heisenberg group. We find sharp, natural geometric conditions ensuring that the level sets of the p-capacitary potential of a bounded annulus in the Heisenberg group are strictly starshaped.

Abstract Background Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. Methods This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. Results In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p

Abstract Background A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. Methods This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Results Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Conclusions Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. Trial registration NCT04411459

Abstract Background To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy. Methods This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. Results 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p

Coagulation disorders and thrombocytopenia are common in patients with septic shock, but only few studies have focused on platelet variables beyond platelet count. The aim of this study was to evaluate whether platelets reactivity predicts sepsis-induced thrombocytopenia in patients with septic shock. We therefore enrolled consecutive patients with septic shock and platelets count >150*103/μL on the day of the diagnosis. Platelets reactivity tests were performed daily from the diagnosis of septic shock until day five; platelet volume distribution and mean platelet volume were also recorded daily. Sepsis-induced thrombocytopenia was defined as a platelet count

Paolo Fogagnolo,1 Chiara Quisisana,1 Anna Caretti,2 Daniele Marchina,1 Michele Dei Cas,2 Ettore Melardi,1 Luca Rossetti1 1Eye Clinic ASST Santi Paolo Carlo, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy; 2Department of Health Sciences, Laboratory of Biochemistry, University of Milan, Milan, ItalyCorrespondence: Paolo FogagnoloEye Clinic ASST Santi Paolo Carlo, Department of Health Sciences, San Paolo Hospital, University of Milan, Via Di Rudinì 8, Milan 20142, ItalyTel +39 02 81844301Email paolo.fogagnolo@unimi.itPurpose: To compare the efficacy of the new lubricating product VisuEvo® (VSE) vs Cationorm® (CTN) in patients with dry eye disease (DED).Methods: Seventy-two patients with evaporative (n=54) and non-evaporative DED (n=18) were included in a multicenter, double-blind, 12-week cross-over study to receive VSE (6 weeks) and CTN (6 weeks) in randomized sequence. After baseline, two visits were performed during each period (intermediate and final visit, respectively at 2 and 6 weeks from the beginning of each period). Primary (tear break-up time, TBUT) and secondary endpoints (Schirmer I, Ferning, blink rate, osmometry, cytokine and lipid expression, ocular surface staining, patient satisfaction, and OSDI score) were compared.Results: Sixty-three patients were evaluated for efficacy and 68 patients for safety. The intergroup differences for mean TBUT values were not significant at any study visit (baseline 3.2 ± 1.5 sec; intermediate visits 4.5 ± 1.9 and 4.5 ± 1.8 sec in VSE and CTN groups, respectively, p = 0.10; final visits 5.4 ± 2.4 and 6.0 ± 3.1, respectively, p=0.63). Also, the assessment of secondary endpoints showed no significant difference between the two groups. The two study treatments were equally effective in evaporative and non-evaporative DED. The safety profile was excellent for both ocular treatments; transient blurred vision was observed in 11 patients only during CTN, 10 patients only during VSE, and 16 during both treatments.Conclusion: VSE was non-inferior to CTN in restoring tear film composition, increasing its stability and reducing ocular surface damage in evaporative and non-evaporative DED patients.Study Identifier: NCT03833882.Keywords: evaporative dry eye disease, tear break-up time, Ocular Surface Disease Index questionnaire, meibomian gland disturbance, glaucoma, ocular surface

Abstract Background Guidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference (A-V O2diff), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion. Methods A prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0–10.0 g/dL within 72 h after ICU admission. The A-V O2diff, central venous oxygen saturation (ScvO2), and oxygen extraction ratio (O2ER) were noted when a patient’s Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O2diff value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as “appropriate” (patient transfused when the A-V O2diff > 3.7 mL or not transfused when the A-V O2diff ≤ 3.7 mL) or “inappropriate” (patient transfused when the A-V O2diff ≤ 3.7 mL or not transfused when the A-V O2diff > 3.7 mL). The primary outcome was 90-day mortality. Results Patients managed with an “appropriate” strategy had lower mortality rates (23/96 [24%] vs. 36/81 [44%]; p = 0.004), and an “appropriate” strategy was independently associated with reduced mortality (hazard ratio [HR] 0.51 [95% CI 0.30–0.89], p = 0.01). There was a trend to less acute kidney injury with the “appropriate” than with the “inappropriate” strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O2diff, but not the ScvO2, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O2diff cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients. Conclusions In anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O2diff. Trial registration ClinicalTrials.gov, NCT03767127 . Retrospectively registered on 6 December 2018.

Purpose. To evaluate compass (CMP), a recently introduced device that combines scanning ophthalmoscopy, automated perimetry, and eye tracking, for fundus-guided perimetry (microperimetry) with the purpose of correlating perimetric retinal sensitivity (PRS) and retinal geographic atrophy (GA) features. Materials and Methods. A retrospective, cross-sectional study was performed in 56 eyes of 43 patients affected by GA. All patients underwent compass 10-2 perimetry, consisting of a full-threshold visual field on fundus photography and an infrared (IR) image of the central 30° of the retina. Data were exported to an Excel sheet. Binarization with black/white (B/W) variables was applied on the compass photo fundus and matched with visual field scores. Patients underwent autofluorescence (AF) and IR images (Heidelberg, Germany): CMP and Heidelberg IR images were homologated by using GIMP software (https://www.gimp.org), and then atrophic areas were manually measured with the ImageJ program. CMP perimetric grid was overlapped with AF and IR pictures by using GIMP, obtaining composite TIFF images, which were then analyzed with the ImageJ greyscale score (GSS) tool. A hyperautofluorescent halo was identified on the GA edges of some patients. Pearson’s correlation between GA size on IR compass and IR Heidelberg and between GSS and PRS values has been calculated; the independent t-test was realized to calculate the correlation between GSS and B/W variables identified on the CMP photo fundus. The Spearman correlation between total deviation and pattern deviation was calculated. Results. The AUC-ROC score between CMP scores and B/W variables was 93,4%. The Spearman correlation between total deviation and pattern deviation was highly significant (p=0,00). The correlation between AF GSS values and PRS was significant (p value = 0,00), the correlation between GSS of hyperautofluorescent points and PRS was significant (p value = 0,00), and the correlation between IR GSS and PRS was significant (p value = 0,00). The correlation between AF GSS and B/W variables was significant (p value = 0,002), the correlation between hyperautofluorescent points and B/W was not significant (p value = 0,40), and the correlation between IR GSS and B/W was significant (p=0,00). Conclusions. Based on our preliminary results, compass seems to be a reliable, quick, and safe device for the anatomical and functional study of GA. The direct visualization of the visual field on the fundus photography as a background allows a precise assessment and clinical monitoring of this disease.

Abstract Background Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL. Methods Patients admitted to the intensive care unit (ICU) with an expected length of mechanical ventilation of 72 h were enrolled in this prospective, observational study. Patients were evaluated, within 24 h from ICU admission and for at least 72 h, in terms of respiratory mechanics, presence of EFL through the PEEP test, daily fluid balance and followed for outcome measurements. Results Among the 121 patients enrolled, 37 (31%) exhibited EFL upon admission. Flow-limited patients had higher BMI, history of pulmonary or heart disease, worse respiratory dyspnoea score, higher intrinsic positive end-expiratory pressure, flow and additional resistance. Over the course of the initial 72 h of mechanical ventilation, additional 21 patients (17%) developed EFL. New onset EFL was associated with a more positive cumulative fluid balance at day 3 (103.3 ml/kg) compared to that of patients without EFL (65.8 ml/kg). Flow-limited patients had longer duration of mechanical ventilation, longer ICU length of stay and higher in-ICU mortality. Conclusions EFL is common among ICU patients and correlates with adverse outcomes. The major determinant for developing EFL in patients during the first 3 days of their ICU stay is a positive fluid balance. Further studies are needed to assess if a restrictive fluid therapy might be associated with a lower incidence of EFL.

Among the potential intellectual outputs of the ENCODE project is the production of a MOOC that introduces teaching staff and scientific experts to the digital transition in the field of ancient writing cultures. The basis for this MOOC is the need to foster awareness of the importance of digital competences and to use a structured framework to introduce people to the available innovative teaching and learning materials and opportunities for organizing (self-)training in this field of research. For specialists in the humanities, there is often an unexpected reluctance to go beyond simply using digital tools and to deepen their understanding of the implications of the digital transitions of research fields, as well as considering the readiness of young graduates to acquire digital competences. This MOOC, which is easily accessible, affordable, sustainable, and flexible, may achieve the initial aim of the project, namely, bridging the gap between the highly specialized competences in the humanities and the innovative digital skills needed in open science practices. The main methodological issue concerns the design and adaptation of cooperative tools in order to implement a common pedagogical approach and to produce MOOC content that integrates the different competences and insights of the project participants. This report on the experiment provides useful insights into the differing expectations of academic staff as content producers, issues surrounding MOOC-cooperative design between universities in different countries, the usability of the tested platform and of the different features provided, and sustainability, as guaranteed through the connection with digital infrastructures. In the concluding section, the originality of the MOOC at a more general scale is emphasized. The ways in which the MOOC can facilitate and support the digital transition are assessed according to the FAIR principles in Higher Education Institutions. Moreover, the MOOC offers models for hands-on experiences of digital training and the evaluation of learning outcomes according to shared European frameworks; it demonstrates the importance of being connected with larger projects and digital infrastructures.