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European citizens and attitudes towards science and technology: what account for societal development and scientific knowledge?
No full textReconstruction of the Lightning Return-Stroke Current from the Radiated Magnetic Field
No full textThis paper presents a new method to solve the inverse problem of reconstructing the lightning return-stroke current from measurements of the radiated magnetic field. Although the lightning channel is still assumed to be straight, vertical and at a known distance from the sensors measuring the fields, no model or channel-base measurement of the current is required, so that, unlike previous approaches to this kind of inverse problem, several assumptions on the current propagation along the channel can be dropped. The method is formulated in the frequency domain and is based on a double Fourier series representation of the unknown current as a function of two variables, i.e., the vertical coordinate and the frequency. The theoretical investigation results in an inversion algorithm, which is tested against simulated data in order to obtain some examples of current reconstruction
Evolution of Self-reported Neuropsychiatric Symptoms After Switching from Dolutegravir/Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide: Results from the Randomized DOBINeuro Trial
No full textIntroduction: Central nervous system adverse events (AE) have been a cause of discontinuation of dolutegravir-containing therapy, especially in combination with abacavir. The main aim of the study was to evaluate whether the switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was associated with a reduction in severity and incidence of neuropsychiatric symptoms compared to continued dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Methods: DOBINeuro is a randomized trial enrolling people living with HIV (PLWH) treated with DTG/ABC/3TC for > 6 months and with HIV-RNA < 50 cps/ml for > 12 months. At baseline, PLWH are randomized to continue DTG/ABC/3TC or switch to BIC/FTC/TAF. The original sample size was 50 PLWH per arm, but the enrollment was prematurely stopped due to a delayed recruitment process. Neuropsychiatric symptoms were evaluated by the self-report Symptom Checklist (SCL)-90-R and the Mini-International Neuropsychiatric Interview Plus. Results: A total of 41 PLWH were enrolled and underwent randomization: 20 were randomized to continue DTG/ABC/3TC and 21 to switch to BIC/FTC/TAF. At baseline, clinical and laboratory characteristics were homogeneous in the two arms. Switching from DTG/ABC/3TC to BIC/FTC/TAF in virologically suppressed PLWH was associated with an improvement in sleep disorders but not in any other neuropsychiatric symptom. Conclusions: Although limited by a low sample size, this study suggests neuropsychiatric tolerability may improve when switching virologically suppressed PLWH from DTG to BIC-based strategies
Early Upper Palaeolithic marine mollusc exploitation at Riparo Bombrini (Balzi Rossi, Italy): shellfish consumption and ornament production
No full textThis research explores the modes of exploitation of marine molluscs at Riparo Bombrini (Ventimiglia, north-west Italy) during the Protoaurignacian and the Early Aurignacian. Our results prove that Early Modern Humans who inhabited the rock- shelter extensively exploited marine malacofauna for both dietary purposes and ornament production, offering new insights into human adaptation to coastal environments during the early phases of the Upper Palaeolithic along the Mediterranean coast. Combining taxonomy and taphonomy, we identified five main categories of shell remains within the assemblage: edible specimens, shell beads, non-worked ornamental shells, accidental introductions, and potential ornamental shells. A total of 91 perforated gastropods were recovered during the excavations of the Early Upper Palaeolithic layers. The orna- ment assemblage shows a certain richness in mollusc species, whose shells were collected dead from the beach. However, a preference for spherical and semi-spherical shells can be observed, highlighting the existence of trends in the selection of shell species for bead production. Use wear analysis demonstrates that some of the shell beads exhibit rounding and polishing around the rim of the perforation, implying that most of them arrived at the site as worn components, possibly forming part of more complex decorative combinations. Finally, the presence of both perforated and unperforated shells interpretable as raw material suggests that the rockshelter served as a “manufacturing site”, where shell ornaments were fabricated, discarded and replaced in new beadworks. This hypothesis is further supported by the presence of broken shell beads, interpretable as manufacturing errors or worn beads ready for replacement
Assessing pathogenicity of germline ATM variation and mechanisms maintaining genomic integrity for response to therapy in a melanoma model
No full textThe Ataxia-Telangiectasia Mutated (ATM) protein kinase plays a key role in the DNA damage response (DDR). It is activated by DNA double-strand breaks (DSB) and initiates repair processes by phosphorylating several key proteins involved in DNA repair, including those in the homologous recombination (HR) pathway. HR-deficient tumors are more susceptible to specific therapies, such as Poly ADP-Ribose Polymerase inhibitors (PARPi), which exploit the DNA repair defects to induce synthetic lethality.
Studies have shown that ATM pathogenic variants can contribute to homologous recombination deficiency (HRD) in various cancers. Little is known about melanoma. We observed that germline variants are enriched in melanoma patients, but to clarify their potential effect in melanoma, a careful functional assessment and classification of the variants is needed, considering that ATM is a hypermutated gene, posing a challenge for their interpretation.
Here, we aimed to functionally assess germline ATM variants in melanoma by establishing primary cell line models to test Loss of Heterozygosity (LOH), HRD, activation of DDR downstream pathway, and response to inhibition of DNA damage repair by PARPi as a potential therapeutic approach.
Despite proven LOH, lack of ATM protein, HRD (determined by the absence of RAD51 foci), and downstream pathway dysregulation, our model did not show sensitivity to PARPi.
Therefore, we assessed the potential role of the Schlafen family member 11 (SLFN11), a helicase involved in regulating cell proliferation, differentiation, and immune response, whose expression sensitizes tumors to PARP inhibitors.
Our ATM mutant cell line lacked SLFN11 protein and featured hypermethylation-mediated silencing of the SLFN11 promoter. Our findings provide functional evidence for the pathogenicity of the germline ATM variation in melanoma through disruption of mechanisms maintaining genomic integrity and show lack of sensitivity to PARPi despite HRD. SLFN11 appears to play a role in regulating sensitivity to agents targeting HR in our model
Prevalence of Dysphagia and Its Health Implications Among Elderly Residents in Long-Term Care Facilities in the Liguria Region (Italy): An Observational Cohort Study
No full text: Background/Objectives: Dysphagia is a common condition among older adults, associated with significant health risks. This prospective, open-label observational cohort study aimed to determine the prevalence of dysphagia and its impact on nutritional status and clinical outcomes in elderly residents of six long-term care facilities. Methods: Patients aged ≥ 65 years were screened using the 3 oz Water Swallow Test (WST); those with dysphagia were followed for 6 months. Nutritional status was evaluated with the Mini Nutritional Assessment short-form (MNA-SF), the Global Leadership Initiative on Malnutrition (GLIM), and the SARC-F questionnaire. Anthropometric and body composition measurements were also obtained. Results: Among 656 patients screened, 188 (28.6%) had dysphagia (median age 90 years; 89.9% females). Mild dysphagia was present in 34.0%, while 66.0% had moderate-to-severe dysphagia. At baseline, patients with moderate-to-severe dysphagia had significantly lower BMI (18.4 vs. 20.6 kg/m2, p = 0.014), smaller calf circumference (24.0 vs. 28.0 cm, p = 0.005), and higher SARC-F score (8 vs. 7, p = 0.028). Bioimpedance analysis showed lower fat mass (6.7 vs. 12.9 kg, p < 0.001) and fat mass% (14.7 vs. 25.4%, p < 0.001), and higher FFM% (85.3 vs. 74.6%, p < 0.001). At 6 months, BMI, calf circumference, handgrip strength, fat mass, and fat mass% resulted significantly lower in patients with moderate-to-severe dysphagia. A total of 23 participants (12.2%) died during follow-up, with a higher mortality rate in the moderate-to-severe group (HR 2.58, 95% CI 1.20-7.59, p = 0.044); aspiration pneumonia was the leading cause (21.7%). Conclusions: Dysphagia significantly affects nutritional status and survival in elderly residents of long-term care facilities. Early personalized nutritional intervention is pivotal to improve outcomes
Exploratory Analysis of Gut Microbiota Profile in Duchenne Muscular Dystrophy (DMD) Patients with Intellectual Disability
No full textThis study investigates the differences in gut microbiota composition between DMD patients with (DMD +) and without (DMD −) intellectual disability (ID) and its potential role in cognitive outcomes. In this study, we assessed the gut microbiota in 50 genetically confirmed DMD patients (median age 13.1 years) using 16S rRNA gene sequencing. Cognitive assessment was performed using the Wechsler Intelligence Scales, with ID defined as an IQ < 70. Stool samples were analyzed, and statistical methods were used to assess alpha- and beta-diversity. Thirty-four percent of patients had ID. No significant differences were found in alpha-diversity or in the Firmicutes/Bacteroidetes ratio. However, beta-diversity analysis revealed significant differences between DMD + and DMD − groups, including, in DMD +, an increased abundance of Propionibacterium and Bifidobacterium, and a reduction in Bulleidia. These bacteria are involved in metabolic pathways that can influence neurological health through the gut-brain axis, particularly via the production of short-chain fatty acids. While these preliminary findings suggest a possible association between gut microbiota profile and cognitive impairment in DMD, further research is needed to explore a causal relationship and consider microbiota-targeted therapeutic strategies
Ex Oriente Lux IV – Nuove indagini e riflessioni sulla Lista Egea
No full textOn the Egyptian rendering of Cretan place-names and the outcome of Proto-Indo-European Voiced Aspirates in Proto-Greek and Macedonia
