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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.