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Recent years have seen a tremendous increase of digital Earth Observation (EO) infrastructures, which provide web-based environments for accessing and processing data in a highly automated and scalable way. However, the current landscape of EO infrastructures and initiatives is fragmented, with various levels of user on-boarding and uptake success. The current work aims to make sense of this complex landscape by providing two main contributions. First, it offers a classification scheme used to review and analyse more than 150 EO infrastructures and initiatives. Then, adopting a user-centric perspective, the main limitations and obstacles currently faced by users when working with the existing EO platforms are identified. For each of these limitations, we propose a number of good practices that could benefit, from a user point of view, the design and functioning of EO platforms. Some technological enablers, i.e. specific resources (such as software components, standards and data encodings) that emerged from the analysis as holding a great potential for improving the usability of existing EO platforms, are finally listed. The work aims to provide a first scientific insight on how to best design and operate EO platforms to maximise the benefits of their user communities.

Carbonic anhydrases (CAs) are widespread metalloenzymes which catalyse the reversible hydration of carbon dioxide (CO2) to bicarbonate (HCO3−) and a proton, relevant in many physiological processes. In the last few years, the involvement of CA activation in different metabolic pathways in the human brain addressed the research to the discovery of novel CA activators. Here, a new series of isoxazoline-based amino alcohols as CA activators was investigated. The synthesis and the CA activating effects towards four human CA isoforms expressed in the human brain, that are hCAs I, II, IV and VII, were reported. The best results were obtained for the (methyl)-isoxazoline-amino alcohols 3 and 5 with KA values in the submicromolar range (0.52–0.86 µM) towards hCA VII, and a good selectivity over hCA I. Being hCA VII involved in brain function and metabolism, the newly identified CA activators might be promising hit compounds with potential therapeutic applications in ageing, epilepsy or neurodegeneration.

ABSTRACTImmune-checkpoint inhibitors (ICI) are highly effective in reinvigorating T cells to attack cancer. Nevertheless, a large subset of patients fails to benefit from ICI, partly due to lack of the cancer neoepitopes necessary to trigger an immune response. In this study, we used the thiopurine 6-thioguanine (6TG) to induce random mutations and thus increase the level of neoepitopes presented by tumor cells. Thiopurines are prodrugs which are converted into thioguanine nucleotides that are incorporated into DNA (DNA-TG), where they can induce mutation through single nucleotide mismatching. In a pre-clinical mouse model of a mutation-low melanoma cell line, we demonstrated that 6TG induced clinical-grade DNA-TG integration resulting in an improved tumor control that was strongly T cell dependent. 6TG exposure increased the tumor mutational burden, without affecting tumor cell proliferation and cell death. Moreover, 6TG treatment re-shaped the tumor microenvironment by increasing T and NK immune cells, making the tumors more responsive to immune-checkpoint blockade. We further validated that 6TG exposure improved tumor control in additional mouse models of melanoma. These findings have paved the way for a phase I/II clinical trial that explores whether treatment with thiopurines can increase the proportion of otherwise treatment-resistant cancer patients who may benefit from ICI therapy (NCT05276284).

Abstract The potential enviromental impact of iodinated (ICAs) and gadolinium-based contrast agents (GBCAs) have recently come under scrutiny, considering the current nonselective wastewater treatment. However, their rapid excretion after intravenous administration could allow their potential recovery by targeting hospital sewage. The GREENWATER study aims to appraise the effective quantities of ICAs and GBCAs retrievable from patients’ urine collected after computed tomography (CT) and magnetic resonance imaging (MRI) exams, selecting ICA/GBCA per-patient urinary excretion and patients’ acceptance rate as study endpoints. Within a prospective, observational, single-centre, 1-year framework, we will enrol outpatients aged ≥ 18 years, scheduled to perform contrast-enhanced CT or MRI, willing to collect post-examination urine in dedicated canisters by prolonging their hospital stay to 1 h after injection. Collected urine will be processed and partially stored in the institutional biobank. Patient-based analysis will be performed for the first 100 CT and 100 MRI patients, and then, all analyses will be conducted on the pooled urinary sample. Quantification of urinary iodine and gadolinium will be performed with spectroscopy after oxidative digestion. The evaluation of the acceptance rate will assess the “environmental awareness” of patients and will aid to model how procedures to reduce ICA/GBCA enviromental impact could be adapted in different settings. Key points • Enviromental impact of iodinated and gadolinium-based contrast agents represents a growing point of attention. • Current wastewater treatment is unable to retrieve and recycle contrast agents. • Prolonging hospital stay may allow contrast agents retrieval from patients’ urine. • The GREENWATER study will assess the effectively retrievable contrast agents’ quantities. • The enrolment acceptance rate will allow to evaluate patients’ “green sensitivity”.

The increasing availability of longitudinal data (repeated numerical observations of the same units at different times) requires the development of flexible techniques to automatically detect errors in such data. Besides standard types of errors, which can be treated with generic error correction techniques, large longitudinal datasets may present specific problems not easily traceable by the generic techniques. In particular, after applying those generic techniques, time series in the data may contain trends, natural fluctuations and possible surviving errors. To study the data evolution, one main issue is distinguishing those elusive errors from the rest, which should be kept as they are and not flattened or altered. This work responds to this need by identifying some types of elusive errors and by proposing a statistical-mathematical approach to capture their complexity that can be applied after the above generic techniques. The proposed approach is based on a system of indicators and works at the formal level by studying the differences between consecutive values of data series and the symmetries and asymmetries of these differences. It operates regardless of the specific meaning of the data and is thus applicable in a variety of contexts. We implement this approach in a relevant database of European Higher Education institutions (ETER) by analyzing two key variables: “Total academic staff” and “Total number of enrolled students”, which are two of the most important variables, often used in empirical analysis as a proxy for size, and are considered by policymakers at the European level. The results are very promising.

Helicobacter pylori (H. pylori) antibiotic resistance is the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistance increases. The aim of this study was to characterize genotypic secondary resistance in a cohort of southern Italian H. pylori patients with at least one previous failure. Such patients collected stool samples using a dedicated kit (THD fecal testTM), and bacterial DNA was extracted and amplified using RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline was assessed using a high-resolution melting curve. We enrolled 50 patients. A total of 72% of patients failed one previous antibiotic course, 16% failed two, 10% failed three, and 2% failed four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin, and 2% for tetracycline. Among the eight clarithromycin-resistant patients, five (62.5%) previously received a clarithromycin-based regimen. The same rate was 33.3% (3/9) for metronidazole. The only tetracycline-resistant patient had received Pylera. In conclusion, our data seem to show that, even though secondary resistance is not very high, resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 PyleraTM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.

Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman’s test for correlation and linear regression. Bland–Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, p < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland–Altman plot found a bias of −0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa (n = 31), we found an excellent r = 0.79 (0.60–0.90, p < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS.

IntroductionDeep brain stimulation of the subthalamic nucleus (STN-DBS) can exert relevant effects on the voice of patients with Parkinson's disease (PD). In this study, we used artificial intelligence to objectively analyze the voices of PD patients with STN-DBS.Materials and methodsIn a cross-sectional study, we enrolled 108 controls and 101 patients with PD. The cohort of PD was divided into two groups: the first group included 50 patients with STN-DBS, and the second group included 51 patients receiving the best medical treatment. The voices were clinically evaluated using the Unified Parkinson's Disease Rating Scale part-III subitem for voice (UPDRS-III-v). We recorded and then analyzed voices using specific machine-learning algorithms. The likelihood ratio (LR) was also calculated as an objective measure for clinical-instrumental correlations.ResultsClinically, voice impairment was greater in STN-DBS patients than in those who received oral treatment. Using machine learning, we objectively and accurately distinguished between the voices of STN-DBS patients and those under oral treatments. We also found significant clinical-instrumental correlations since the greater the LRs, the higher the UPDRS-III-v scores.DiscussionSTN-DBS deteriorates speech in patients with PD, as objectively demonstrated by machine-learning voice analysis.

Abstract Artificial intelligence (AI) and its different approaches, from machine learning to deep learning, are not new. We discuss here about the declaration of AI in the title of those articles dealing with AI. From 1990 to 2021, while AI articles in the PubMed increased from 300 to 59,596, the percentage declaring AI in the title describes a U-like-shaped curve: about 30% in early 1990s, less than 13% in 2005–2014, again 30% in 2020–2021. A similar trend was observed for AI in medical imaging. While the initial decline could be due to the establishment of AI methods, the recent increase could be related to the capacity of AI to outperform humans, especially in image recognition, fuelled by the adoption of graphic processing units for general purpose computing. The recent increase may also be due to the relevance of open issues about AI, including the standardisation of methods, explainability of results, and concerns about AI-induced epoch-making transformations: to say “We are using AI” in the title may also reflect these concerns.

Abstract Background Wandering spleen is a rare condition, which is characterized by augmented mobility of the spleen, due to congenital or acquired causes. It is more frequent in multiparous women, but only a few cases are reported during pregnancy. Wandering spleen is usually asymptomatic until the onset of its possible complications, and this can mislead clinicians in reaching the correct diagnosis. Case presentation We report the case of a wandering spleen with acute splenic infarction in a pregnant woman and its minimally invasive surgical treatment, focusing on the clinical and radiological findings that could mislead or drive clinicians to the right diagnosis, or a potential disaster. Conclusions Splenic preservation in the wandering spleen where it is safe and possible is the main goal of the treatment. Clinical and radiological findings are the most relevant elements to drive surgical treatment. To reach the best and opportune treatment for the patient, the wandering spleen is an insidious condition and must be included in the differential diagnosis in the acute abdomen diagnostic process.

Abstract Cancer genomics and cancer mutation databases have made an available wealth of information about missense mutations found in cancer patient samples. Contextualizing by means of annotation and predicting the effect of amino acid change help identify which ones are more likely to have a pathogenic impact. Those can be validated by means of experimental approaches that assess the impact of protein mutations on the cellular functions or their tumorigenic potential. Here, we propose the integrative bioinformatic approach Cancermuts, implemented as a Python package. Cancermuts is able to gather known missense cancer mutations from databases such as cBioPortal and COSMIC, and annotate them with the pathogenicity score REVEL as well as information on their source. It is also able to add annotations about the protein context these mutations are found in, such as post-translational modification sites, structured/unstructured regions, presence of short linear motifs, and more. We applied Cancermuts to the intrinsically disordered protein AMBRA1, a key regulator of many cellular processes frequently deregulated in cancer. By these means, we classified mutations of AMBRA1 in melanoma, where AMBRA1 is highly mutated and displays a tumor-suppressive role. Next, based on REVEL score, position along the sequence, and their local context, we applied cellular and molecular approaches to validate the predicted pathogenicity of a subset of mutations in an in vitro melanoma model. By doing so, we have identified two AMBRA1 mutations which show enhanced tumorigenic potential and are worth further investigation, highlighting the usefulness of the tool. Cancermuts can be used on any protein targets starting from minimal information, and it is available at https://www.github.com/ELELAB/cancermuts as free software.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. Methods We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. Results We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). Conclusions The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.

La erosión hídrica es un proceso que combina factores naturales y antrópicos, con efectos sobre la productividad sistémica y sobre la calidad de los recursos naturales. El objetivo de este trabajo fue realizar estimaciones de pérdidas potenciales (EP) y actuales (EA) de suelo en sistemas de producción (SP) con diferente cobertura y características topográficas, dentro de los límites de la cuenca del Arroyo Ludueña (Santa Fe, Argentina), utilizado la Ecuación Universal de Pérdida de Suelos y el programa EROSION 6.0. Para doce SP se modelaron 10 años de rotaciones bajo siembra directa: agricultura continua con predominio de soja (AC), agricultura continua intensiva con alta proporción de gramíneas (ACi) y rotaciones agrícola-ganaderas con diferentes proporciones de pasturas (AG 40:60 y AG 30:70). La EP estimada afectaría la estabilidad sistémica ya que supera las 18 tn.ha-1.año-1 en todos los casos. La EA fue un 18, 30 y 53% mayor en AG 70:30, ACi y AC respecto a AG 60:40, con tasas máximas y mínimas para el total de simulaciones de 7,2 y 1,0 tn.ha-1.año-1. Las características del relieve evidenciaron que por encima del valor 0,131 del factor LS (longitud y gradiente de pendiente), la AC no sería sustentable por las altas tasas de EA y porque estos SP están asociados a vías de escurrimiento que pueden facilitar transporte de agroquímicos hacia sectores más bajos. La información generada a escala predial permitiría avanzar en el estudio de la dinámica del proceso erosivo y su impacto a nivel de cuencas.

The grain size, nutrients, and metals contents of sediments are important tracers for reconstructing the origin of the contaminants and the pathway of the sediments from the source to the sink. This is particularly important in areas with high geological variability and a high demographic pressure. The origin and distribution of contaminants and nutrients allow us to identify the source-to-sink pathway of the sediments. In particular, the Sarno River is one of the main contributing sources of anthropogenic contaminants due to the outflow from the large surrounding large industrial area. Geochemical and physical parameters of sediments were analyzed along a transect from the coastline to a water depth of 112 m, with the objective of exploring the spatial variability of sediment contamination in the continental shelf of Naples Bay. The latter is characterized by a complex geological area and is subject to river inflow from a highly industrialized area. The data have been analyzed using principal component analysis (PCA), hierarchical correlation analysis (CA), and analysis of variance (ANOVA). To distinguish between a natural and anthropogenic origin of contaminants and to construct the source-to-sink pathway, the relationship between geochemical and physical data and their distribution was examined, and the results were compared with published data collected onshore. Four distinct sectors with different associations of metals, grain size, and total organic carbon have been recognized: I) offshore Vesuvius volcano, the occurrence of coarse-grained sediments, associated with As, Fe, Mn, and low TOC values, suggests a natural origin of the contaminant due to the volcanic nature of the substrate; II) offshore the Sarno River, the presence of Cr, Cd, Cu, Pb and Zn, associated with the high TOC content, suggests an anthropogenic origin for the contaminants; III) offshore Sorrento Peninsula, the presence of As, Fe, Mn, and some gravel made up of pumice and bioclasts indicate a predominance of contaminants of natural origin; and IV) finally, the distal part is not subjected to a primary terrestrial input. Metals contamination of anthropogenic origin and the organic matter in sediments decreased rapidly with distance from the coast highlighting the main deposition area close to the river discharge.

Book Review

IntroductionThe study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators.MethodsCase collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate.ResultsAmong the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP.DiscussionAccording to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.

BackgroundStuttering is a childhood-onset neurodevelopmental disorder affecting speech fluency. The diagnosis and clinical management of stuttering is currently based on perceptual examination and clinical scales. Standardized techniques for acoustic analysis have prompted promising results for the objective assessment of dysfluency in people with stuttering (PWS).ObjectiveWe assessed objectively and automatically voice in stuttering, through artificial intelligence (i.e., the support vector machine – SVM classifier). We also investigated the age-related changes affecting voice in stutterers, and verified the relevance of specific speech tasks for the objective and automatic assessment of stuttering.MethodsFifty-three PWS (20 children, 33 younger adults) and 71 age−/gender-matched controls (31 children, 40 younger adults) were recruited. Clinical data were assessed through clinical scales. The voluntary and sustained emission of a vowel and two sentences were recorded through smartphones. Audio samples were analyzed using a dedicated machine-learning algorithm, the SVM to compare PWS and controls, both children and younger adults. The receiver operating characteristic (ROC) curves were calculated for a description of the accuracy, for all comparisons. The likelihood ratio (LR), was calculated for each PWS during all speech tasks, for clinical-instrumental correlations, by using an artificial neural network (ANN).ResultsAcoustic analysis based on machine-learning algorithm objectively and automatically discriminated between the overall cohort of PWS and controls with high accuracy (88%). Also, physiologic ageing crucially influenced stuttering as demonstrated by the high accuracy (92%) of machine-learning analysis when classifying children and younger adults PWS. The diagnostic accuracies achieved by machine-learning analysis were comparable for each speech task. The significant clinical-instrumental correlations between LRs and clinical scales supported the biological plausibility of our findings.ConclusionAcoustic analysis based on artificial intelligence (SVM) represents a reliable tool for the objective and automatic recognition of stuttering and its relationship with physiologic ageing. The accuracy of the automatic classification is high and independent of the speech task. Machine-learning analysis would help clinicians in the objective diagnosis and clinical management of stuttering. The digital collection of audio samples here achieved through smartphones would promote the future application of the technique in a telemedicine context (home environment).

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

We provide data describing all the largest Italian Universities from several perspectives, including scientific research, administrative and economic point of view. In particular, associated with each University, we have the following data.(a) The list of the most representative research keywords (single words and bigrams), automatically extracted from titles, abstracts and other possible metadata of all the research publications available for that University in Scopus database at October 2022.(b) The Extended_name of the University, Status, University_Type, State_status, number of Managerial and Administrative Staff, Teaching Staff and Researchers, Phd Diplomas, Phd Enrollments, Enrolled Undergraduates, Enrolled Graduates, Graduates, Master I Lv Graduates, Enrolled Master's Degree I Lv, Master II Lv, Graduates Enrolled, Master II Lv, Graduates Specialistic Schools and Enrolled Specialistic Schools were extracted from USTAT database for the years 2016–2018.(c) The data of Educational Income, Income from Commissioned Research and Technology Transfer, Income from Research with competitive funding, Own Income, Contributions from others (private), Contributions from others (public), Contributions from universities, Contributions from the European Union and the Rest of the World, Contributions from other local governments, Contributions Regions and Autonomous Provinces, MIUR and other central government grants, Operating Costs, Current Management Costs, Managerial and administrative personnel costs, Research and teaching staff cost, Cost of Lecturers and Researchers, Cost Scientific Collaborators, Cost of Contract Teachers, Cost of Language Experts, Other research and teaching personnel costs, Personnel Costs, Scientific equipment, Concessions, licenses and trademarks, Patent rights are extracted from the unique University Balance Sheet of each university for the years 2016–2018.These data were of difficult availability; they have been extracted from several heterogeneous sources and have been automatically checked, cleaned from errors, integrated, and missing values have been imputed as much as possible. However, due to large missing portions in the sources, they still contain several missing parts.Nonetheless, they represent a powerful snapshot of the Italian Universities, and can be of interest to researchers for many analyses of the Italian academic world. All the sources of the openly available data are provided.

IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin–angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.

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Objetivo. La mortalidad por cáncer en la región centro de Argentina está dentro de las más elevadas del país. Dos posibles escenarios ambientales podrían explicar esta situación, su actividad agrícola y la calidad del agua de consumo. El objetivo del estudio es evaluar la interacción existente entre estas variables. Métodos. Estudio retrospectivo de diseño ecológico. Se analizaron decenios de superficies sembradas totales (SST) y el porcentaje de población expuesta a niveles elevados de arsénico y nitratos en aguas de consumo en relación con las tasas de mortalidad total (TMT) y órgano-específicas (TME); se calculó el coeficiente de correlación de Spearman. Resultados. Se hallaron correlaciones positivas y significativas entre los dos primeros decenios de SST y el primer decenio de TMT, así como correlaciones con cáncer de pulmón, páncreas y colon en hombres; y con cáncer de colon en mujeres. Los niveles elevados de arsénico se asocian con las TMT en ambos sexos y en todos los decenios, aunque de manera específica con cáncer de pulmón en hombres. No se hallaron correlaciones significativas con nitratos. Conclusiones. La asociación entre las SST y las TMT y TME presentan mayor intensidad cuanto más cerca están entre ellas temporalmente, y expresan un mayor impacto de los cultivos más antiguos. La asociación entre las TMT y el consumo de aguas arsenicales, así como la hallada en TME de pulmón en hombres y colon en mujeres, muestran que esta exposición histórica es central para entender las condiciones epidemiológicas regionales. Se deben explorar fuerzas sinérgicas entre estas variables.

El cambio climático influye sobre los regímenes hidrológicos de los ríos. Las bajantes en épocas de sequía transforman negativamente a los humedales. La alteración estructural y funcional que producen en ellos, modifica principalmente la productividad vegetal y los suelos, y esto se agrava cuando ocurren incendios. Para los años 2017, 2019, 2020 y 2022 se estimó la cobertura de agua del Delta Superior del río Paraná mediante imágenes satelitales, y se evaluaron los efectos en algunas propiedades edáficas causados por incendios en un sector de una isla del mismo humedal. La cobertura de agua se estimó a partir de mosaicos de imágenes satelitales Sentinel 2 A/B. Las tareas de geoprocesamiento se efectuaron en Google Earth Engine. Se caracterizó el estado de los suelos en 18 posiciones que tuvieron distintas severidades de quema. El efecto combinado de una bajante pronunciada en el nivel del río con una sequía climática muy intensa, condicionaron fuertemente la superficie cubierta por agua en el área del humedal. Los incendios tuvieron efectos negativos, principalmente en los suelos de los sitios con mayor severidad de quema en dos variables químicas y en una física-mecánica. De repetirse estas combinaciones ambientales el humedal incrementará riesgosamente su vulnerabilidad ecosistémica

Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based GLUT4 trafficking in human and mouse muscle fibers and L6 rat muscle cells. We found GLUT4 localized on the microtubules in mouse and human muscle fibers. Pharmacological microtubule disruption using Nocodazole (Noco) prevented long-range GLUT4 trafficking and depleted GLUT4-enriched structures at microtubule nucleation sites in a fully reversible manner. Using a perifused muscle-on-a-chip system to enable real-time glucose uptake measurements in isolated mouse skeletal muscle fibers, we observed that Noco maximally disrupted the microtubule network after 5 min without affecting insulin-stimulated glucose uptake. In contrast, a 2-hr Noco treatment markedly decreased insulin responsiveness of glucose uptake. Insulin resistance in mouse muscle fibers induced either in vitro by C2 ceramides or in vivo by diet-induced obesity, impaired microtubule-based GLUT4 trafficking. Transient knockdown of the microtubule motor protein kinesin-1 protein KIF5B in L6 muscle cells reduced insulin-stimulated GLUT4 translocation while pharmacological kinesin-1 inhibition in incubated mouse muscles strongly impaired insulin-stimulated glucose uptake. Thus, in adult skeletal muscle fibers, the microtubule network is essential for intramyocellular GLUT4 movement, likely functioning to maintain an insulin-responsive cell surface recruitable GLUT4 pool via kinesin-1-mediated trafficking.

Objective:. To evaluate the influence of enhanced recovery pathway (ERP) on patient-reported outcome measures (PROMs) and return to intended oncologic therapy (RIOT) after colorectal surgery. Background:. ERP improves early outcomes after colorectal surgery; however, little is known about its influence on PROMs and on RIOT. Methods:. Prospective multicenter enrollment of patients who underwent colorectal resection with anastomosis was performed, recording variables related to patient-, institution-, procedure-level data, adherence to the ERP, and outcomes. The primary endpoints were PROMs (administered before surgery, at discharge, and 6 to 8 weeks after surgery) and RIOT after surgery for malignancy, defined as the intended oncologic treatment according to national guidelines and disease stage, administered within 8 weeks from the index operation, evaluated through multivariate regression models. Results:. The study included 4529 patients, analyzed for PROMs, 1467 of which were analyzed for RIOT. Compared to their baseline preoperative values, all PROMs showed significant worsening at discharge and improvement at late evaluation. PROMs values at discharge and 6 to 8 weeks after surgery, adjusted through a generalized mixed regression model according to preoperative status and other variables, showed no association with ERP adherence rates. RIOT rates (overall 54.5%) were independently lower by aged > 69 years, ASA Class III, open surgery, and presence of major morbidity; conversely, they were independently higher after surgery performed in an institutional ERP center and by ERP adherence rates > median (69.2%). Conclusions:. Adherence to the ERP had no effect on PROMs, whereas it independently influenced RIOT rates after surgery for colorectal cancer.

Background Loss of Ambra1 (autophagy and beclin 1 regulator 1), a multifunctional scaffold protein, promotes the formation of nevi and contributes to several phases of melanoma development. The suppressive functions of Ambra1 in melanoma are mediated by negative regulation of cell proliferation and invasion; however, evidence suggests that loss of Ambra1 may also affect the melanoma microenvironment. Here, we investigate the possible impact of Ambra1 on antitumor immunity and response to immunotherapy.Methods This study was performed using an Ambra1-depleted BrafV600E/Pten−/− genetically engineered mouse (GEM) model of melanoma, as well as GEM-derived allografts of BrafV600E/Pten−/− and BrafV600E/Pten−/−/Cdkn2a−/− tumors with Ambra1 knockdown. The effects of Ambra1 loss on the tumor immune microenvironment (TIME) were analyzed using NanoString technology, multiplex immunohistochemistry, and flow cytometry. Transcriptome and CIBERSORT digital cytometry analyses of murine melanoma samples and human melanoma patients (The Cancer Genome Atlas) were applied to determine the immune cell populations in null or low-expressing AMBRA1 melanoma. The contribution of Ambra1 on T-cell migration was evaluated using a cytokine array and flow cytometry. Tumor growth kinetics and overall survival analysis in BrafV600E/Pten−/−/Cdkn2a−/− mice with Ambra1 knockdown were evaluated prior to and after administration of a programmed cell death protein-1 (PD-1) inhibitor.Results Loss of Ambra1 was associated with altered expression of a wide range of cytokines and chemokines as well as decreased infiltration of tumors by regulatory T cells, a subpopulation of T cells with potent immune-suppressive properties. These changes in TIME composition were associated with the autophagic function of Ambra1. In the BrafV600E/Pten−/−/Cdkn2a−/− model inherently resistant to immune checkpoint blockade, knockdown of Ambra1 led to accelerated tumor growth and reduced overall survival, but at the same time conferred sensitivity to anti-PD-1 treatment.Conclusions This study shows that loss of Ambra1 affects the TIME and the antitumor immune response in melanoma, highlighting new functions of Ambra1 in the regulation of melanoma biology.

Abstract Background Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. Methods We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). Results In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. Conclusions These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.