IL CASO ITALIANO PER LA MOBILITÀ SOSTENIBILE ED ACCESSIBILITÀ NELLE AREE INTERNE E MARGINALI

Accessibility is one of the key elements for implementing sustainable development and cohesion policies, in terms of which it is expressed through the availability of an adequate transport system for access as easy as possible at least to basic services. The internal and marginal areas are usually territories identified within the rural and mountainous regions, areas with a low level of accessibility, characterized by low settlement density and accentuated depopulation phenomena. The concept of "internal" or "marginal" area cannot be defined in a restrictive and univocal way. Mobility as a Service (MaaS) is an emerging concept of new integrated transport services, and although it is often developed and studied from an urban point of view, in inland and marginal areas - with low population, long distances and low coverage tariff capacity - could improve the efficiency of the mobility system through the integration of different types of transport. The redesign of services in internal/marginal areas within the integrated local development projects are developed within the National Strategy of Internal Areas (SNAI)

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores ((Formula presented.) and (Formula presented.)). By applying a logistic regression with both IPGS, ((Formula presented.) (or indifferently (Formula presented.)) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized. Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases. Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis. Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 (www.clinicaltrial.org

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10−8). A total of 113 variants were associated with survival at P-value < 1.0 × 10−5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

From green energy to green logistics: an application to freight distribution

The paper presents an overview of urban freight distribution and of shared individual services, and the preliminary results of an application within an articulated two-year research project, which aims to integrate the production of green-energy inside port areas and its consumption to feed fuelled electric vehicles (FEVs) for transport and logistic services

Mobility Control Centre and Artificial Intelligence for Sustainable Urban Districts

The application of artificial intelligence (AI) to dynamic mobility management can support the achievement of efficiency and sustainability goals. AI can help to model alternative mobility system scenarios in real time (by processing big data from heterogeneous sources in a very short time) and to identify network and service configurations by comparing phenomena in similar contexts, as well as support the implementation of measures for managing demand that achieve sustainable goals. In this paper, an in-depth analysis of scenarios, with an IT (Information Technology) framework based on emerging technologies and AI to support sustainable and cooperative digital mobility, is provided. Therefore, the definition of the functional architecture of an AI-based mobility control centre is defined, and the process that has been implemented in a medium-large city is presented

A sustainable approach for planning of urban pedestrian routes and footpaths in a pandemic scenario

The coronavirus disease (COVID-19) pandemic has forced national and local governments to re-consider the relationship between mobility, urban space and health in order to ensure physical distancing while meeting the travel needs of inhabitants. In the first stage, corresponding to the expansion of infection, mobility was limited to essential workers and freight. In the second stage, with the easing of restrictions, limitations still remained for public transport. Limitations associated with perceived risk of infection significantly influenced travel behaviors, pushing a modal repositioning in demand to active mobility (walking, cycling, and use of micro-mobility). On the other hand, the World Health Organization (WHO) guidelines on mobility during the COVID outbreak are mostly directed at dedicating more urban space to cyclists and pedestrians, especially in densely populated urban areas, thus avoiding crowding on public transport and the use of private cars. In the same direction, the National Association of City Transportation Officials (NACTO, 2020) went during periods of stabilization and long-term recovery. It suggests policies and measures for the cities mobility to help people maintain physical distance while moving around the city. In the given conditions, walking becomes predominant for a sustainable mobility scenario, and structural measures (widening of the pathway) or regulatory measures (regulation of pedestrian flows) can be adopted withing the given strategy. Current pedestrian infrastructural offer is severely limited in functional terms by the urban planning and development, therefore measures oriented to enhance non-motorized mobility require the development and planning of new public spaces and infrastructures for pedestrian mobility within the urban layout. Policy makers and town planners need to rethink urban spaces and mobility in the pedestrian perspective. A methodology for classification of pathways, by capacity and level of service, is presented in the paper, on which to base strategies, policies and specific measures to verify pedestrian mobility demand

Difficoltà diagnostiche e terapeutiche nei GIST: nostre considerazioni su un caso clinico

Gastrointestinal stromal tumours account for fewer than 1% of malignant tumours of the digestive system. Analysing a case referred to us for observation, we review the literature with regard to diagnostic and therapeutic difficulties. A 68-year-old patient was referred to our institute with a diagnosis of "retroperitoneal haematoma". Computerised tomography showed a solid mass with a liquid component, occupying almost the whole of the abdominal cavity. An ultrasonography-guided biopsy examination suggested the presence of a sarcoma. Exploratory laparotomy and the histological examination, which was positive for CD117, CD34 and the smooth muscle marker caldesmon, allowed a diagnosis of gastrointestinal stromal tumour to be made. Thus, no thoroughly reliable and accurate diagnosis of gastrointestinal tumour can be made without surgical exploration and consequent histological and immunohistochemical examinations that still represent the only method capable of confirming or ruling out a diagnosis of gastrointestinal stromal tumour. Such tumours are rare and aggressive and their prognosis is closely related to tumour size and the mitotic index per high power field. Radical resection affords the only possibility of long-term survival

Pancreatite acuta postoperatoria. Esperienza personale e revisione della letteratura

AIM: Acute postoperative pancreatitis is a rare event, but, at the same time, it represents one of the most frightening complications, because it is associated with high mortality risk. METHODS: From January 1985 to December 2005, we observed 30 cases (12 males, 18 females) of acute postoperative pancreatitis. Twenty cases of low and medium gravity have been treated with only medical therapy, 10 cases, instead, have requested surgical therapy (necrosectomy and application of abdominal drains in 7 cases, necrosectomy and ileostomy in 1 case, necrosectomy and colostomy in 1 case, ligation of pancreatic vessels in 1 case of haemorrhagic pancreatitis). RESULTS: In the form of low and medium gravity, fast and pharmacological support (somatostatin and gabexate mesilate) are enough to resolve the event. In the form of high gravity the early surgical treatment has represented the clinical solution in 7 patients, while 3 others patients have died for septic and metabolic complication. CONCLUSIONS: Still today acute postoperative pancreatitis represents a frightening complication associated with high mortality risk that the surgeon has to treat with great care to avoid each bilio-pancreatic injury