Search

Bien que l’œuvre de Ferdinand de Saussure ait été diffusée à travers le monde, sa pensée a été en grande partie reconstruite et interprétée par ses étudiants et disciples. Ses écrits authentiques revêtent pourtant, de notre point de vue, une importance fondamentale : ils mettent en lumière l’attention que Saussure accorde à la terminologie linguistique. Lui-même utilise souvent un vocabulaire particulier. Il forge des néologismes ou confère un sens nouveau à des mots existants, il emploie quelques termes de façon éphémère, change la dénotation de certains concepts au fil du temps, créant ainsi une terminologie qui lui est propre. Dans cet article, nous présentons le premier thésaurus-lexique électronique de la terminologie linguistique saussurienne, en cours de création. La population de ce lexique est constituée par une nomenclature mise à jour, comprenant non seulement la terminologie répertoriée par Godel et Engler mais également de nouveaux termes extraits de manuscrits actuellement à l’étude. À travers ce lexique, nous nous proposons de fournir une représentation structurée de la terminologie saussurienne, de définir le contenu sémantique de chacun des termes ainsi que la nature des relations qui les unissent. À cet effet, nous avons choisi de customiser le modèle lexical SIMPLE qui, dans le panorama de la Lexicographie Computationnelle, s’est imposé comme standard de facto et offre une représentation sémantique hautement structurée des unités lexicales. Le processus de customisation du modèle de base s’est tout d’abord focalisé sur la conception d’une ontologie lexicale de domaine (ontologie SIMPLE_FdS), et sa traduction dans le langage de représentation d’ontologie Web OWL. Puis, les deux autres composants du modèle de base, i.e. un réseau de relations sémantiques et un ensemble de traits sémantiques, ont été également adaptés aux exigences du domaine traité. Les moyens expressifs jugés appropriés pour rendre compte de la terminologie saussurienne ont été retenus tandis que des traits et relations spécifiques ont été créés afin d’exprimer des propriétés et des liens qui caractérisent l’organisation conceptuelle de ce domaine de la connaissance. Le lexique est ici illustré par des exemples d’entrées lexicales et le potentiel de la base de connaissance par des requêtes sur les données mémorisées. L’organisation structurée de la connaissance lexicale et la richesse de la représentation sémantique font de ce lexique un outil de recherche sémantique particulièrement performant et qui devrait contribuer de manière significative à mieux maîtriser le vocabulaire saussurien et à éclairer certains aspects originaux de la pensée du maître genevois.

Aims: To evaluate the determinants of cardiovascular (CV) protection in men and women treated with glucagon-like peptide-1 receptor agonists (GLP1-RA)., Methods: Retrospective cohort study of 550 patients (43% women), with and without established CV disease, followed at a single center after the first prescription of a GLP1-RA. We analyzed the determinants of major adverse cardiovascular events (MACE) in men and women., Results: The rate of MACE was similar between sexes. In primary prevention, among men, older age (HR 1.13, 95 % C.I. 1.05-1.22; P = 0.001) and GLP-1 RA withdrawal by time (HR 2.77, 95 % C.I. 1.15-6.68; P = 0.023) increased the HR for MACE. Among women, significant predictors of MACE were diabetes duration (HR 1.05, C.I. 1.01-1.10; P = 0.020), GLP-1 withdrawal by time (HR 2.84, 95 % C.I. 1.13-7.10; P = 0.026) and BMI at GLP-1 RA withdrawal (HR 1.08, 95 % C.I. 1.01-1.15; P = 0.026). For individuals with prior CV disease, the HR for MACE was solely impacted by GLP-1 withdrawal over time in males (HR 2.18, 95 % C.I. 1.10-4.30; P = 0.025) and by older age at GLP-1 RA initiation (HR 1.17, 95 % C.I. 1.03-1.33; P = 0.015) in females., Conclusions: Although MACE rates were similar, the factors contributing to MACE differed by sex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Neuroendocrine neoplasms (NENs) are tumors that arise from cells of the endocrine system and are most common in the gastrointestinal tract, the pancreas, and the lungs. Their incidence is rapidly increasing and the therapeutic options available are limited., Methods: Since the immune system can interfere with tumor growth and response to therapy, using flow cytometry we investigated the immunophenotype in samples of peripheral blood leukocytes from patients with pancreatic (Pan-NENs) and pulmonary NENs (Lung-NENs). Moreover, we performed a multiplex analysis of 13 key cytokines and growth factors essential for the immune response in the plasma of NEN patients and controls., Results: Patients presented with a higher percentage of granulocytes, a lower percentage of lymphocytes, and an increase in the granulocytes to lymphocytes ratio compared to healthy donors. These alterations were more marked in patients with metastasis. Somatostatin analogs (SSAs) restored the immunophenotype of patients to that seen in healthy donors. Finally, Pan-NEN patients showed a higher plasma concentration of IP-10, MCP-1, and IL-8 compared to healthy donors, suggesting a potential role for these cytokines as diagnostic biomarkers., Conclusion: This study highlighted differences in the immunophenotype of patients with Pan- and Lung-NENs compared to healthy individuals; these alterations were partially restored by therapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Postnatal human cytomegalovirus (HCMV) infection in newborns is well characterized for preterm infants but less so for term infants. We sought to analyze the rates and routes of HCMV transmission in full-term infants during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV-DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5 × 10 2 HCMV-DNA copies/mL in infants' saliva swabs. Maternal neutralizing antibody serum titer, HCMV-specific T-cell response, and HCMV glycoprotein B immunoglobulin G on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first 3 months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine, and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV-DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV-specific CD4 + T-cells with long-term memory phenotype was observed in women with HCM-DNA-positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva has a minor role whereas the role of vaginal secretions is negligible., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Aim: To describe the development of the AWARE App, a novel web application for the rapid assessment of cardiovascular risk in Type 2 Diabetes Mellitus (T2DM) patients. We also tested the feasibility of using this App in clinical practice., Methods: Based on 2019 European Society of Cardiology/European Association for the Study of Diabetes criteria for cardiovascular risk stratification in T2DM, the AWARE App classifies patients into very high (VH CVR ), high (H CVR ) and moderate (M CVR ) cardiovascular risk categories. In this retrospective clinical study, we employed the App to assess the cardiovascular risk of T2DM patients, while also collecting data about current glycaemic control and pharmacological treatment., Results: 2243 T2DM consecutive patients were evaluated. 72.2% of the patients were VH CVR , 8.9% were H CVR , 0.8% were M CVR while 18.2% did not fit into any of the risk categories and were classified as "moderate-to-high" (MH CVR ). Compared with the other groups, patients with VH CVD were more frequently ≥ 65 years old (68.9%), with a longer disease duration (≥ 10 years [56.8%]), a history of cardiovascular disease (41.4%), organ damage (35.5%) and a higher numbers of cardiovascular risk factors. Patients with MH CVD generally had disease duration < 10 years (96%), younger age (50-60 years [55%]), no history of cardiovascular disease, no organ damage, and 1-2 cardiovascular risk factors (89%). Novel drugs such as Glucagon Like Peptyde 1 Receptor Agonists or Sodium-Glucose Linked Transporter 2 inhibitors were prescribed only to 26.3% of the patients with VH CVR and to 24.7% of those with H CVR . Glycaemic control was unsatisfactory in this patients population (HbA1c 7.5 ± 3.4% [58.7 ± 13.4 mmol/mol])., Conclusions: The AWARE App proved to be a practical tool for cardiovascular risk stratification of T2DM patients in real-world clinical practice., (© 2023. The Author(s).)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in cardiovascular outcome trials in type 2 diabetes mellitus. However, the most convincing evidence was obtained in subjects with established cardiovascular (CV) disease. We analyzed the determinants of GLP-1 RA-mediated CV protection in a real-world population of persons with type 2 diabetes with and without a history of CV events with long-term follow-up., Methods: Retrospective cohort study of 550 individuals with type 2 diabetes (395 in primary CV prevention, 155 in secondary CV prevention), followed at a single center after the first prescription of a GLP-1 RA between 2009 and 2019. CV and metabolic outcomes were assessed., Results: Median duration of follow-up was 5.0 years (0.25-10.8) in primary prevention and 3.6 years (0-10.3) in secondary prevention, with a median duration of treatment of 3.2 years (0-10.8) and 2.5 years (0-10.3) respectively. In the multivariable Cox regression model considering GLP-1 RA treatment as a time-dependent covariate, in the primary prevention group, changes in BMI and glycated hemoglobin did not have an impact on MACE risk, while age at the time of GLP-1 initiation (HR 1.08, 95% CI 1.03-1.14, p = 0.001) and GLP-1 RA cessation by time (HR 3.40, 95% CI 1.82-6.32, p < 0.001) increased the risk of MACE. Regarding the secondary prevention group, only GLP-1 RA cessation by time (HR 2.71, 95% CI 1.46-5.01, p = 0.002) increased the risk of MACE. With respect to those who withdrew treatment, subjects who continued the GLP-1 RA had significantly greater weight loss and lower glycated hemoglobin levels during follow-up., Conclusions: In this real-world type 2 diabetes population, discontinuation of GLP-1 RA treatment was associated to a higher risk of major cardiovascular events, in both subjects with and without a history of CV events., (© 2023. The Author(s).)

Objectives: Human cytomegalovirus (HCMV) non-primary infections can occur in pregnant women and may result in congenital infection. Comprehensive studies investigating the frequency, characteristics, risk factors and immune response of non-primary infection in pregnancy are missing, while the rate of vertical transmission is not known., Methods: HCMV non-primary infection was investigated prospectively in 250 pregnant women. Blood and urine samples as well as saliva and vaginal swabs were collected at 13, 21 and 31 weeks of gestation and at delivery. HCMV-DNA and specific IgG and IgM levels were determined., Results: Overall, 105/250 pregnant women (42.0%) developed non-primary infection. HCMV-DNA was detected more frequently in vaginal secretions (84/250 of the women, 33.6%) than in urine (35/250, 14.0%), saliva (26/250, 10.4%) and blood (7/250, 3.0%). The rate of HCMV non-primary infection increased significantly with the progression of pregnancy (from 12.9% in the first trimesters of gestation to 21.9% at delivery, p < 0.01). IgM was detected in 25/250 of the women (10.0%), with no association with non-primary infection, while anti-gB IgG was significantly higher (p < 0.01) in women with non-primary infection. Age and close contact with children were not associated with non-primary infection. No woman with non-primary infection transmitted the infection to the fetus (95% confidence interval of transmission rate: 0-3.5%)., Discussion: Although HCMV non-primary infection is frequent during pregnancy, the rate of congenital infection as a consequence of non-primary infection is likely to be ≤ 3.5%., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated., Methods: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls., Results: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls., Conclusion: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.

Background and Objective: Prediction of fractures in cancer survivors exposed to hormone-deprivation therapies (HDTs) is a challenge since bone loss is rapid and severe, and determinants of fractures in this setting are still largely unknown. In this study we investigated reliability of the WHO Fracture Risk Assessment Tool (FRAX) and bone mineral density (BMD) to identify subjects developing vertebral fractures during HDTs., Design: Five-hundred-twenty-seven consecutive subjects (429 females with breast cancer, 98 males with prostate cancer; median age 61 years), under HDTs for at least 6 months, were evaluated for vertebral fractures by a radiological and morphometric approach, in relationship with FRAX score, body mass index (BMI), BMD, age and duration of HDTs., Results: Vertebral fractures were found in 140 subjects (26.6%) and spine deformity index was significantly associated with duration of HDTs (rho 0.38; p <  0.001). Only in females, vertebral fractures were significantly associated with FRAX score for major fractures [OR 1.08; P  < 0.001]. The best cut-off of FRAX score for major fractures, as calculated by receiving operating characteristic (ROC) analysis was 6.35%. In males, however, vertebral fractures were significantly and independently associated with BMI ≥ 25 Kg/m 2 (OR 17.63; P  < 0.001), BMD T-score below -1.0 SD at any skeletal site (OR 7.79; P  < 0.001) and gonadotropin-releasing hormone agonists (GnRHa) plus abiraterone treatment (OR 11.51; P  = 0.001)., Conclusions: FRAX and BMD may be useful for predicting vertebral fractures in subjects undergoing HDTs, but the thresholds seem to be lower than those used in the general population. High BMI is a determinant of vertebral fractures in males under HDT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mazziotti received consultancy fees from Novartis, Ipsen, Eli Lilly and lecture fees from Amgen and Abiogen, outside the submitted work. Dr. Vena received grants from IBSA Pharmaceutical outside the submitted work. Dr. Zucali reports receiving, outside the submitted work, personal fees for an advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, Astrazeneca, Roche, and Bayer. Dr. Torrisi received research grants from Pfizer, consultancy fees from MSD and lecture fees from Pfizer, Eli Lilly, EISAI and Genomic Health outside the submitted work. Dr. Lania received grants from Pfizer and consultancy fees from Ipsen, outside the submitted work. Dr Berruti reports receiving grants and personal fees from Janssen Cilag, grants and personal fees from Astellas, and personal fees from Bayer outside the submitted work., (© 2022 The Authors.)

Derangement of pituitary hormone axes can induce changes in bone remodeling and metabolism with possible alterations in bone microarchitectural structure and increased susceptibility to fractures. Vertebral fractures (VFs), which are a hallmark of skeletal fragility, have been described in a very large number of patients with pituitary diseases. These fractures are clinically relevant, since they predispose to further fractures and may negatively impact on patients' quality of life. However, the management of skeletal fragility and VFs in the specific setting of pituitary diseases is a challenge, since the awareness for this disease is still low, prediction of VFs is uncertain, the diagnosis of VFs cannot be solely based on a clinical approach and also needs a radiological and morphometric approach, the risk of fractures may not be decreased via treatment of pituitary hormone disorders, and the effectiveness of bone-active drugs in this setting is not always evidence-based. This review is an update on skeletal fragility in patients with pituitary diseases, with a focus on clinical and therapeutic aspects concerning the management of VFs., (© 2021. Hellenic Endocrine Society.)

Background: Medication adherence is a determinant of therapeutic outcomes in osteoporotic patients treated with bisphosphonates. In this monocentric study, we evaluated whether the regular drug administration may influence the effectiveness of denosumab in preventing vertebral fractures (VFs) in real-world clinical practice., Methods: Two-hundred and four women (median age 75 years, range: 54-90 years) under treatment with denosumab for post-menopausal osteoporosis were longitudinally evaluated for incident radiological VFs and changes in lumbar spine bone mineral density (BMD) in relationship with medication adherence. All patients were persistent with denosumab treatment (i.e., maximum delay in administration of a single denosumab dose: 90 days). Patients were defined adherent to denosumab therapy when the drug was administered every 6 months ±28 days., Results: One-hundred-seventy-three patients (84.4%) were adherent to denosumab therapy, whereas the remaining 31 patients (15.6%) received in delay one or more denosumab doses (cumulative delay: 52 days, range 29-183 days). Fourteen patients (6.9%) experienced incident VFs during the follow-up (median duration: 30 months, range: 18-48 months), in relationship with non-adherence to denosumab therapy (hazard ratio 4.44; 95% CI: 1.01-19.47) and smaller increase in lumbar spine BMD (hazard ratio 0.85, 95% CI: 0.76-0.94)., Conclusions: In post-menopausal women at high risk of fractures, the small delay in the administration of denosumab (i.e., not uncommon in clinical practice) was associated with a significant increase in incidence of VFs. Preservation of standard dosing schedule appears to be an important determinant of denosumab effectiveness in the real-life clinical practice.

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination., Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination., Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% ± 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression., Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients.

Background: Nutrition-sensitive programs can accelerate progress in addressing malnutrition. However, evidence gaps exist related to their effectiveness and how to optimize program design and implementation., Objective: We present the process the International Food Policy Research Institute and the World Food Programme (WFP) used to develop nutrition-sensitive program guidance and plans for improving program effectiveness and contributing to the evidence base through rigorous evaluations., Methods: A 5-step process, using principles of design thinking (a systematic, iterative analytical approach to problem solving), was used to develop, test, and refine WFP's nutrition-sensitive guidance. The guidance focuses on improving nutrition outcomes for nutritionally vulnerable groups across the life cycle: women and children in the first 1000 days, preschoolers, schoolchildren, and adolescents., Results: Through iterative consultations, we created WFP's nutrition-sensitive guidance that includes harmonized theories of change across WFP's programs; 7 opportunities to enhance the programs' nutrition-sensitivity; and mapping of these opportunities to WFP programs and key evidence gaps. This guidance has been rolled out to WFP's offices worldwide to support improved nutrition outcomes. Finally, several evaluation designs have been proposed to fill identified evidence gaps., Conclusions: By leveraging our implementation-research partnership, we expect that WFP's programs will be more effective and cost effective for improving nutrition. This can be assessed through coupling newly designed nutrition-sensitive programs with rigorous evaluations. Evaluation results will be used to refine WFP's nutrition-sensitive guidance and improve their programs globally. This guidance, and creation process, could be useful for others interested in designing nutrition-sensitive programs and increasing program effectiveness for nutrition.

Starting from racemic 4-hydroxy-4-methyl-2-cyclopentenone, a family of enantiopure carbanucleosides locked in the northern conformation has been synthesized. The use of ionic liquids was determinant in the last step resulting in a tangible increase of the yields and dramatic reduction of reaction times and volumes of organic solvents. To our knowledge, this is the first example of the use of ionic liquids in the coupling of carbasugars with heterocyclic bases.