Search

Abstract Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.

The progression of logistics and supply chain management (LSCM) has been significantly influenced by various factors, such as structural changes, increased customer awareness, digitalization, resilience requirements, and a growing emphasis on sustainability. This intricacy emphasizes the need for a comprehensive reevaluation of essential professional competencies. This study aims to provide a thorough and comprehensive examination of the existing academic literature to identify the critical skills that are crucial to the current LSCM environment.The paper is a systematic analysis based on bibliographic methods. Descriptive, bibliographic coupling, and conceptual analyses will be carried out using two distinct software applications: Biblioshiny for Bibliometrix (employed for descriptive and conceptual analyses) and VOSViewer (utilized for bibliographic coupling). A systematic examination of the clusters derived from bibliographic analyses will then be undertaken to derive more nuanced insights.The analysis of academic literature indicates that much of the attention in the LSCM field has been directed toward technical proficiencies, quantitative abilities, and operational expertise. The overemphasis on hard skills suggests a potential oversight in recognizing the full spectrum of competencies required for success in the evolving landscape of LSCM. Our research reveals a discernible trend towards emphasizing soft skills, as evidenced by the presence of two out of the four clusters focusing on competencies of this nature.The practical application of this research involves assisting professionals in creating personalized training plans, aiding logistics associations in developing a broader range of skills in response to significant changes and helping universities in designing specialized courses on soft skills for logistics. The theoretical aspect delves into the intricate relationship between soft skills and technical proficiency in logistics, yielding critical insights into how Human Resources can effectively contribute to enhancing a company's overall value.

Abstract We capitalized on the respiratory bodily illusion that we discovered in a previous study and called ‘Embreathment’ where we showed that breathing modulates corporeal awareness in men. Despite the relevance of the issue, no such studies are available in women. To bridge this gap, we tested whether the synchronization of avatar-participant respiration patterns influenced females’ bodily awareness. We collected cardiac and respiratory interoceptive measures, administered body (dis)satisfaction questionnaires, and tracked participants’ menstrual cycles via a mobile app. Our approach allowed us to characterize the ‘Embreathment’ illusion in women, and explore the relationships between menstrual cycle, interoception and body image. We found that breathing was as crucial as visual appearance in eliciting feelings of ownership and held greater significance than any other cue with respect to body agency in both women and men. Moreover, a positive correlation between menstrual cycle days and body image concerns, and a negative correlation between interoceptive sensibility and body dissatisfaction were found, confirming that women’s body dissatisfaction arises during the last days of menstrual cycle and is associated with interoception. These findings have potential implications for corporeal awareness alterations in clinical conditions like eating disorders and schizophrenia.

Climate change is projected to increase the frequency and intensity of extreme rainfall events in the Mediterranean region, increasing runoffs of terrestrial matter into coastal waters. To evaluate the consequences of terrestrial runoff for plankton key processes, an in situ mesocosm experiment was conducted for 18 d in the spring of 2021 in the coastal Mediterranean Thau Lagoon. Terrestrial runoff was simulated in replicate mesocosms by adding soil from an adjacent oak forest that had matured in water from the main tributary river of the lagoon. Automated high-frequency monitoring of dissolved oxygen, chlorophyll a fluorescence, salinity, light, and temperature was combined with manual sampling of organic and inorganic nutrient pools, pH, carbonate chemistry, and maximum quantum yield (Fv:Fm) of photosystem II (PSII). High-frequency data were used to estimate the gross primary production (GPP) of oxygen, community respiration (CR), and phytoplankton growth (μ) and loss (L) rates. During the first half of the experiment (d2–d11), the simulated runoff reduced light availability (−52 %), chlorophyll a concentrations (−70 %), and phytoplankton growth rates (−53 %). However, phytoplankton maintained a certain level of primary production by increasing its photosynthetic efficiency. Meanwhile, the runoff enhanced CR (+53 %), shifting the metabolic status (GPP : CR) of the system toward heterotrophy and increasing the partial pressure of carbon dioxide (pCO2), potentially switching the direction of the air–sea CO2 exchange. However, during the second part of the experiment (d11–d17), remineralized nutrients boosted phytoplankton growth (+299 %) in the terrestrial runoff treatment but not its loss rates, leading to phytoplankton biomass accumulation and suggesting a mismatch between phytoplankton and its predators. Our study showed that a simulated terrestrial runoff significantly affected key plankton processes, suggesting that climate-change-related increases in runoff frequency and intensity can shift the metabolic balance of Mediterranean coastal lagoons towards heterotrophy.

We analyze different Latin American scenarios from a perspective that brings together contributions from performance studies and critical theories of colonialism. In this crossroads we put in dialogue two artistic devices (the work Tierra by Regina José Galindo and Reunión: Lof Lauken Winkul Mapu by Dani Zelko) with the notion of conquistuality, by the Argentine anthropologist Rita Segato. We examine the productivity of these materials (theoretical and artistic) to reflect on recent events that, from our perspective, are part of a colonial history.

Abstract Background Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

The long story of NK cells started about 50 y ago with the first demonstration of a natural cytotoxic activity within an undefined subset of circulating leukocytes, has involved an ever-growing number of researchers, fascinated by the apparently easy-to-reach aim of getting a “universal anti-tumor immune tool”. In fact, in spite of the impressive progress obtained in the first decades, these cells proved far more complex than expected and, paradoxically, the accumulating findings have continuously moved forward the attainment of a complete control of their function for immunotherapy. The refined studies of these latter years have indicated that NK cells can epigenetically calibrate their functional potential, in response to specific environmental contexts, giving rise to extraordinarily variegated subpopulations, comprehensive of memory-like cells, tissue-resident cells, or cells in various differentiation stages, or distinct functional states. In addition, NK cells can adapt their activity in response to a complex body of signals, spanning from the interaction with either suppressive or stimulating cells (myeloid-derived suppressor cells or dendritic cells, respectively) to the engagement of various receptors (specific for immune checkpoints, cytokines, tumor/viral ligands, or mediating antibody-dependent cell-mediated cytotoxicity). According to this picture, the idea of an easy and generalized exploitation of NK cells is changing, and the way is opening toward new carefully designed, combined and personalized therapeutic strategies, also based on the use of genetically modified NK cells and stimuli capable of strengthening and redirecting their effector functions against cancer.

Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.

Abstract (Mg,Fe)O ferropericlase‐magnesiowüstite has been proposed to host the majority of Earth's sodium, but the mechanism and capacity for incorporating the alkali cation remain unclear. In this work, experiments in the laser‐heated diamond anvil cell and first‐principles calculations determine the solubility of sodium and favorability of sodium incorporation in iron‐rich magnesiowüstite relative to (Mg,Fe)SiO3 bridgmanite. Reaction of Mg/(Mg + Fe) (Mg#) 55 and 28 olivine with NaCl at 33–128 GPa and 1600–3000 K produces iron‐rich magnesiowüstite containing several percent sodium, while iron‐rich bridgmanite contains little to no detectable sodium. In sodium‐saturated magnesiowüstite, sodium number [Na/(Na + Mg + Fe)] is 2–5 atomic percent at pressures below 60 GPa and drastically increases to 10–20 atomic percent at deep lower mantle pressures. For these two compositions, there is no significant dependence of the results on Mg#. Our calculations not only show consistent results with experiments but further indicate that such an increase in solubility and partitioning of Na into magnesiowüstite is driven by the spin transition in iron. These results provide fundamental constraints on the crystal chemistry of sodium at lower‐mantle conditions. If the sodium capacity of (Mg,Fe)O is not strongly dependent on Mg#, (Mg,Fe)O in the lower mantle may have the capacity to store the entire sodium budget of the Earth.

Abstract Background The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls. Methods A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non-carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment. Results The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001). Conclusions The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.

The aim of this contribution is to advance the hypothesis of a possible reading under the prism of the melodramatic mode of narratives belonging to the corpus of the generation of Argentinean HIJOS that focus on the theme of intergenerational affective bonds. After a reflection on the characteristics of melodrama and its tradition in Latin America, attention is focused on mapping texts with a testimonial matrix that nevertheless present melodramatic features, to then analyze the specific cases of two novels –Una muchacha muy bella (2013) by Julián López and Magdalufi (2018) by Verónica Sánchez Viamonte– in which the melodramatic mode functions as the articulating matrix.

Whole-body positron emission tomography (PET)–computed tomography (CT) imaging performed for oncological purposes may provide additional parameters such as the coronary artery calcium (CAC) and epicardial adipose tissue (EAT) volume with cost-effective prognostic information in asymptomatic people beyond traditional cardiovascular risk factors. We evaluated the feasibility of measuring the CAC score and EAT volume in cancer patients without known coronary artery disease (CAD) referred to whole-body 18F-FDG PET–CT imaging, regardless of the main clinical problem. We also investigated the potential relationships between traditional cardiovascular risk factors and CAC with EAT volume. A total of 109 oncological patients without overt CAD underwent whole-body PET–CT imaging with 18F-fluorodeoxyglucose (FDG). Unenhanced CT images were retrospectively viewed for CAC and EAT measurements on a dedicated platform. Overall, the mean EAT volume was 99 ± 49 cm3. Patients with a CAC score ≥ 1 were older than those with a CAC = 0 (p < 0.001) and the prevalence of hypertension was higher in patients with detectable CAC as compared to those without (p < 0.005). The EAT volume was higher in patients with CAC than in those without (p < 0.001). For univariable age, body mass index (BMI), hypertension, and CAC were associated with increasing EAT values (all p < 0.005). However, the correlation between the CAC score and EAT volume was weak, and in multivariable analysis only age and BMI were independently associated with increased EAT (both p < 0.001), suggesting that potential prognostic information on CAC and EAT is not redundant. This study demonstrates the feasibility of a cost-effective assessment of CAC scores and EAT volumes in oncological patients undergoing whole-body 18F-FDG PET–CT imaging, enabling staging cancer disease and atherosclerotic burden by a single test already included in the diagnostic work program, with optimization of the radiation dose and without additional costs.