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Marine microalgae offer significant potential as sustainably cultivable microorganisms for the biorefining of a diverse array of functional metabolites. In this study, three species of marine microalgae, Tetraselmis chuii Butcher CCAP 66/21B (Chlorophyte), Phaeodactylum tricornutum Bohlin CCAP 1052/1 (Diatom) and Amphidinium carterae Hulburt CCAP 1102/8 (Dinoflagellate), were batch cultivated and their biomass retrieved for analysis in terms of pigment and fatty acid composition as well as bioactivity potential. Sequential solvent maceration of the biomass returned extracts was used to determine antioxidant capacity and assess their growth inhibition potential against A549 (a human lung carcinoma) and MCF-7 (a breast carcinoma) cell lines. The extracts of A. carterae showed higher antioxidant capacity (≤ 33.5 μmol Trolox Equivalent mg Recovered Dried Material‒1) compared to the other extracts. No major cytotoxic activity nor production of reactive oxygen species was observed using the extracts of T. chuii and P. tricornutum. However, the methanolic extraction of A. carterae inhibited the growth of both A549 and MCF-7 cells (< 4%) at 25, 50 and 100 µg ml−1 concentrations, as determined using the MTS assay and AO/PI cell staining. Microalgal metabolites have the potential for practical applications in a variety of industrial sectors. The absence of toxicity and substantial antioxidant potential of extracts of T. chuii and P. tricornutum confirm their suitability for incorporation into animal feeds or human nutrition supplements. A. carterae also appears to be a promising source of bioactives that can be further valorized via multi-compound biorefinery pipelines.

The Arctic is as a key place to perform environmental measurements given its combination of reduced human activity and increased sensitivity to climate change. The Svalbard archipelago constitutes an invaluable measurement location, due to its ease of access and the presence of the Ny-Ålesund research center. Sensors are usually not designed to sustain prolonged periods of time in demanding environments like the Arctic; therefore, chances of failures, drift, and errors are higher than elsewhere. Maintenance and calibration of these sensors must be rigorous and frequent, to avoid poor-quality data, or even their loss. Within the frame of EURAMET EMRP project “MeteoMet 2”, calibration of the temperature sensors hosted by the Climate Change Tower (CCT), a unique research facility designed to monitor lower-atmosphere profiles of several meteorological quantities, has been performed. The calibration campaign pointed out sensor errors up to 1 °C and corrected the measurements, straightening the skewed temperature profiles. Absolute calibration uncertainties have been evaluated at ∼0.2 °C, less than half of those stated by the manufacturer, while an evaluation of relative uncertainties yielded values of just few 0.01 °C. This experience stimulated the creation of an in-situ calibration facility, to the benefit of the whole scientific community based in Ny-Ålesund.

This article addresses the poetic inflection of the last decade in Peruvian poetry; At the same time, it proposes that, in this period, there has been a notable shift in writing by women as an expression of a period characterized by “empolleramiento”. We maintain that this turn is characterized by irreverence, by the hybrid management of forms and by a unique way of tuning into reality. Our study focuses on three creators: Gloria Alvitres, Karuraqmi Puririnay and Lourdes Aparición. To analyze their texts, we appeal to a concept associated with Andean clothing, namely: the skirt. Thus, brooding will be used as an inclusive notion in which the situation of women who are not in the center, who are not part of the canon and who were despised by political power is described and the characteristics of these emerging poetics are examined

Statement of the Problem: The satisfaction of patients with dentures on implants has different points of view that become fundamental aspects for the development of research on the quality of life of these patients, the eventual biomechanical complications to which these prostheses and implants can be subjected, and design considerations for cantilever extensions.Purpose: The objective of research was to assess the implants and prosthesis survival rates, biomechanical complications relative to the length of the distal extensions (cantilevers), and the satisfaction of the patients with a fixed implant-supported full-arch fiber-reinforced composites prosthesis.Materials and Method: A retrospective clinical and radiographic cohort study was developed. Clinical records of a selected cohort were analyzed according to inclusion and exclusion criteria. Data on a patient who underwent to fixed implant-supported full-arch fiber-reinforced composites prosthesis at least of five years of function were collected. Data analysis was performed using Kaplan-Meier curves and Fisher's Exact Test. P values less than 0.05 were considered statistically significant.Results: After insertion, 1 of 29 prostheses failed, the overall prosthetic survival rate observed at 5 years was 96.5%. Of the 120 implants placed in 28 patients, only 4 patients experienced loss of an implant during the 5 years of observation; the implant survival rate throughout the observation period was 86.2%. Distal extension seems to negatively affect the prognosis of implant-supported rehabilitation. Regarding the level of satisfaction of the patient with the prosthesis, none reported being uncomfortable or dissatisfied neither with their appearance nor with the taste of food throughout the studied period.Conclusion: No relevant associations were found between the variables involved. The study found the improvement in quality of life following the installation of fixed rehabilitation on the patients. Once the potential benefits of patients are obtained, controlled clinical trials are encouraged.

Abstract In the design process of large adaptive mirrors numerical simulations represent the first step to evaluate the system design compliance in terms of performance, stability and robustness. For the next generation of Extremely Large Telescopes increased system dimensions and bandwidths lead to the need of modeling not only the deformable mirror alone, but also all the system supporting structure or even the full telescope. The capability to perform the simulations with an acceptable amount of time and computational resources is highly dependent on finding appropriate methods to reduce the size of the resulting dynamic models. In this paper we present a framework developed together with the company Microgate to create a reduced order structural model of a large adaptive mirror as a preprocessing step to the control system simulations. The reduced dynamic model is then combined with the remaining system components allowing to simulate the full adaptive mirror in a computationally efficient way. We analyze the feasibility of our reduced models for Microgate’s prototype of the adaptive mirror of the Giant Magellan Telescope.

Abstract A large number of non‐native trees (NNTs) have been introduced globally and widely planted, contributing significantly to the world's economy. Although some of these species present a limited risk of spreading beyond their planting sites, a growing number of NNTs are spreading and becoming invasive leading to diverse negative impacts on biodiversity, ecosystem functions and human well‐being. To help minimize the negative impacts and maximize the economic benefits of NNTs, Brundu et al. developed eight guidelines for the sustainable use of NNTs globally—the Global Guidelines for the Use of NNTs (GG‐NNTs). Here, we used an online survey to assess perceptions of key stakeholders towards NNTs, and explore their knowledge of and compliance with the GG‐NNTs. Our results show that stakeholders are generally aware that NNTs can provide benefits and cause negative impacts, often simultaneously and they consider that their organization complies with existing regulations and voluntary agreements concerning NNTs. However, they are not aware of or do not apply most of the eight recommendations included in the GG‐NNTs. We conclude that effectively managing invasions linked to NNTs requires both more communication efforts using an array of channels for improving stakeholder awareness and implementation of simple measures to reduce NNT impacts (e.g. via GG‐NNTs), and a deeper understanding of the barriers and reluctance of stakeholders to manage NNT invasions. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications.

The relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) and phytocannabinoids/endocannabinoids (pCBs/eCBs) has been investigated in a variety of models of peripheral illnesses, with little clarification on their interaction within the central nervous system (CNS). In this context, evidence suggests that the Nrf2-pCBs/eCBS interaction is relevant in modulating peroxidation processes and the antioxidant system. Nrf2, one of the regulators of cellular redox homeostasis, appears to have a protective role toward damaging insults to neurons and glia by enhancing those genes involved in the regulation of homeostatic processes. Specifically in microglia and macroglia cells, Nrf2 can be activated, and its signaling pathway modulated, by both pCBs and eCBs. However, the precise effects of pCBs and eCBs on the Nrf2 signaling pathway are not completely elucidated yet, making their potential clinical employment still not fully understood.

This article outlines the two main purposes of the Vatican Library digitization project (long-term digital preservation and dissemination of contents), focusing on the exploitation of digital assets and providing the humanities with a new way to study the ancient roots of knowledge. The article describes the LTDP (Long Term Data Preservation) pipeline, and the choice of preservation format based on sustainability factors and focuses on the LTDP archives requirements in light of the UNI 11845:2022 standard. The dissemination pipeline describes the digital library platform and demonstrates the Vatican Library’s adoption of the IIIF protocol (International Image Interoperability Framework). Finally, the article describes a pilot project relating to the use of AI for the recognition of iconographic details in illuminations, with the peculiarity of managing the results of the artificial neural network within IIIF annotations.

Project-based organizations (PBOs) rely on project management as their core business process. These organizations are characterized by their disaggregated structure and diverse authority distribution, leading to complications in synchronizing projects, governance, and functional divisions. In this regard, there is a need of a tool to manage this complexity. This paper introduces a novel approach – the IModel- for modeling, designing and analyzing PBOs, following the Design Science Research Method, that seeks to is creating an artifact that solves a real-world problem in a specific context. This artifact is developed through a conceptual integration between project management (PM) and enterprise architecture (EA) sources based on ontologies. Ontologies are powerful, machine-readable graph-structured models which enables sophisticated models’ reasoning and querying. IModel fuses the organizational domain from the ArchiMate EA language with PM insights from PMBOK 7th edition. The resulting IModel has been submitted to an expert’s judgement to assess its intended purposes as well, its potential to be applied in the real-world to support the PBO.

Nature-based Solutions (NBS) are increasingly recognized as relevant strategies for mitigating the pressures coming from urbanization and climate change to build resilient and sustainable cities. However, securing financing for urban NBS is a persistent barrier for their widespread implementation. Therefore, understanding how to realize (co-)finance and funding by attracting resources from specific stakeholders – namely those that benefit from NBS - is essential to their expansion. While the need for NBS co-finance has been acknowledged, the funders' perspective on NBS has remained largely conceptual. Through a systematic review of the scientific literature this study identifies barriers and corresponding strategies for financing urban NBS from the funders'-oriented perspective. Knowledge sharing, fostering of innovative and alternative financing models and collaboration, also for co-financing, are among the most cited strategies to leverage other financial resources for NBS implementation and overcoming the budget shortfalls generally affecting public actors. We conclude by proposing future research avenues. Particularly, we suggest that the role of specific classes of stakeholders, namely corporations, the insurance sector, real estate firms and water utilities, should be investigated further since their contributions is likely to be relevant for the upscaling of NBS.

Peru faces substantial social and economic inequality. Rural communities experience social exclusion through the undervaluation of their cultural heritage and native languages, creating significant barriers to their personal and professional growth. Higher education scholarships aim to address this issue, yet educational institutions—typically based in urban areas—often present a disorienting environment for these students, affecting both their academic performance and overall experience. This study proposes an audiovisual literacy program for scholarship students at a private university in Peru, designed to enhance their identity and development within an urban setting. Findings suggest that such a program can foster positive change by reinforcing students’ sense of identity, valuing their cultural heritage, and strengthening their connection to the university environment.

ABSTRACTIndividuals with Inflammatory Bowel Disease (IBD) are more susceptible to experiencing severe complications of COVID-19 if infected. Nevertheless, sub-optimal immunization rates have been reported among these patients. Our study aims to assess COVID-19 VH among a global population of patients with IBD and to investigate the role of healthcare professionals, particularly gastroenterologists, in promoting immunization. Twenty-six studies were systematically selected from scientific articles in the MEDLINE/PubMed, WoK, and Scopus databases from January 1, 2020, to September 15, 2023. The pooled prevalence of COVID-19 VH was 27.2% (95%CI = 20.6–34.2%). A significant relationship was evidenced between COVID-19 vaccine compliance and receiving advice from gastroenterologists or healthcare providers (OR = 2.77; 95%CI = 1.79–4.30). By leveraging their knowledge of IBD, familiarity with patient histories, and trusted patient-doctor relationships, gastroenterologists are pivotal in promoting vaccination. This patient-centered care is crucial in increasing vaccine acceptance among individuals with IBD, contributing to better public health outcomes.

AbstractCorporate Social Responsibility (CSR) promotes sustained productivity, attention to the environment, and various improvements in its operations. All this to benefit internal and external customers. However, it is difficult to implement a comprehensive version of CSR in workers, who find obstacles to satisfy an optimal balance between productivity and family life. This has motivated the emergence of the concept of Corporate Family Responsibility (CFR), which formalizes the presence of the CSR in the workers, through processes and transformations within the company. This article carries out a diagnosis of the Peruvian situation around CFR, using the theory of institutional pressures, system thinking, and stakeholder theory, to formulate a functional CFR proposal. Its attributes are coincident with the Great Place to Work (GPTW) indicators in the companies with the highest score.

AbstractResearch is a common feature in developed countries. Those who dedicate themselves to this activity produce important tools for individual, community, and national development. However, developing countries suffer the opposite situation. In these nations, little investment is devoted to research, and they lack dissemination mechanisms, while offering few possibilities of capitalizing on its benefits. For this reason, the present study carries out an analysis of the relevance of the research, an establishment of these proposal needs in the Latin American context, and the establishment of the bases for a systemic proposal based on a research training program. In that sense, this proposal takes into account the limited economic resources and the lack of investigative culture in the Latin American territory. It is accompanied by a prototype of the training program, based on good practices and lessons learned so far.

This study explored the land use land cover (LULC) change over 45 years (1975 -2020) in the world’s largest mangrove forest, Sundarbansusing Landsat imagery. LULC maps were created with same-season imagery with the lowest cloud cover at four intervals: 1975, 1990, 2005, and 2020. Maximum likelihood classification (MLC) was applied to assign five classes: dense forest, moderate forest, sparse forest, barren land, and water body. Accuracy assessment was carried out with 250 control points for each year resulting in overall accuracy and kappa coefficient ranging from 84.8% to 90.0% and 0.81 to 0.87, respectively. Results show dense forest at its highest cover in 1975 and then decreasing by an estimated annual rate of 1.3% from 1975 to 2020, but not consistently. Dense forest class mostly turned moderate and sparse; most of the sparse forest class turned to barren land. Most of the barren lands were located near the boundary between forest and human settlement, and these two classes were more frequent in the Indian part of Sundarbans than in the Bangladesh part. The conclusion is that the time-series of remote sensing data can validly support effective forest management by identifying space and time changes in the biodiversity of Sundarbans.

Abstract Rationale Elevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen‐presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood. Objective We aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin‐induced pulmonary fibrosis in mice. Methods We used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c‐DTR‐Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin‐induced lung inflammation and fibrosis. Results Fourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c‐DTR‐Tg mice protected against bleomycin‐induced mortality and pulmonary fibrosis compared to wild‐type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis‐related mRNAs (Collagen‐1α1 and α‐SMA). Increased anti‐inflammatory cytokine IL‐10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL‐1β, with lung hyper‐inflammation and early fibrosis development. Conclusion Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality.

Climate change triggers abiotic stress, such as drought and high salinity, that can cause osmotic stress. Water availability can limit plant growth, and the root tip tissues initially sense it. Most experiments destined to understand root growth adaptation to osmotic stress apply homogeneous high osmotic potentials (osmotic shock) to shoots and roots. However, this treatment does not represent natural field conditions where a root may encounter increasing osmotic potentials while exploring the soil. Osmotic shock severely reduces root growth rate, decreasing cell division in the proximal meristem and reducing mature cell length. In this work, we developed an in vitro osmotic gradient experimental system with increasing osmotic potentials. The system generates a controlled osmotic gradient in the root growth zone while exposing the aerial tissues to control conditions. The osmotic gradient system allowed Arabidopsis seedlings of Col-0 and ttl1 mutant (affected in the gene TETRATRICOPEPTIDE THIOREDOXIN-LIKE 1 (TTL1)) to sustain proper root growth for 25 days, reaching osmotic potentials of -1.2 MPa. We demonstrated that roots of seedlings grown in the osmotic gradient sustain a higher root growth rate than those that were grown under a homogeneous high osmotic potential. Furthermore, we found out that the expression of some genes is modified in the roots grown in the osmotic gradient compared to those grown in osmotic shock. Our data indicate that using an osmotic gradient can improve our understanding of how plants respond to osmotic stress and help find new genes to improve plant field performance.

Organic matter is crucial in aerosol–climate interactions, yet the physicochemical properties and origins of organic aerosols remain poorly understood. Here we show the seasonal characteristics of submicron organic aerosols in Arctic Svalbard during spring and summer, emphasizing their connection to transport patterns and particle size distribution. Microbial-derived organic matter (MOM) and terrestrial-derived organic matter (TOM) accounted for over 90% of the total organic mass in Arctic aerosols during these seasons, comprising carbohydrate/protein-like and lignin/tannin-like compounds, respectively. In spring, aerosols showed high TOM and low MOM intensities due to biomass-burning influx in the central Arctic. In contrast, summer exhibited elevated MOM intensity, attributed to the shift in predominant atmospheric transport from the central Arctic to the biologically active Greenland Sea. MOM and TOM were associated with Aitken mode particles (100 nm diameter), respectively. This association is linked to the molecular size of biomolecules, impacting the number concentrations of corresponding aerosol classes. These findings highlight the importance of considering seasonal atmospheric transport patterns and organic source-dependent particle size distributions in assessing aerosol properties in the changing Arctic.

Abstract Extracellular vesicles (EVs) are promising natural nanocarriers for the delivery of therapeutic agents. As with any other kind of cell, red blood cells (RBCs) produce a limited number of EVs under physiological and pathological conditions. Thus, RBC-derived extracellular vesicles (RBCEVs) have been recently suggested as next-generation delivery systems for therapeutic purposes. In this paper, we show that thanks to their unique biological and physicochemical features, RBCs can be efficiently pre-loaded with several kinds of molecules and further used to generate RBCEVs. A physical vesiculation method, based on “soft extrusion”, was developed, producing an extremely high yield of cargo-loaded RBCEV mimetics. The RBCEVs population has been deeply characterized according to the new guidelines MISEV2023, showing great homogeneity in terms of size, biological features, membrane architecture and cargo. In vitro preliminary results demonstrated that RBCEVs are abundantly internalized by cells and exert peculiar biological effects. Indeed, efficient loading and delivery of miR-210 by RBCEVs to HUVEC has been proven, as well as the inhibition of a known mRNA target. Of note, the bench-scale process can be scaled-up and translated into clinics. In conclusion, this investigation could open the way to a new biomimetic platform for RNA-based therapies and/or other therapeutic cargoes useful in several diseases.

Abstract Background Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status—whether it is nodulated or not—can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit. Results Here, we analyzed soybean roots’ differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination. Conclusions Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.

Abstract Background Sleep is vital for maintaining individuals’ physical and mental health and is particularly challenged during pregnancy. More than 70% of women during the gestational period report insomnia symptoms. Sleep dysfunction in the peripartum increases the risk for a cascade of negative health outcomes during late pregnancy, birth, and postpartum. While psychological interventions are considered the first line treatment for sleep difficulties, they are still scarcely offered during pregnancy and there is a lack of longitudinal research combining psychological and physiological indices. Methods The present protocol outlines a randomized controlled trial aimed at testing the long-term effectiveness of an automatized digitalized psychoeducational intervention for insomnia for expectant mothers complaining insomnia symptoms without comorbidity. Outcomes include physiological, hormonal, and subjective indices of maternal psychopathology, stress, and emotional processes, and sleep and wellbeing of the family system. The trial is part of a longitudinal study evaluating expectant mothers from early pregnancy (within the 15th gestational week) to 6-months postpartum through 6 observational phases: baseline (BSL), 6- and 12-weeks from BSL (FU1-FU2), 2-to-4 weeks after delivery (FU3), and 3- and 6-months after delivery (FU4-5). We plan to recruit 38 women without sleep difficulties (Group A) and 76 women with sleep difficulties (Group B). Group B will be randomly assigned to digital psychological control intervention (B1) or experimental psychoeducational intervention targeting insomnia (B2). At 3 time points, an ecological-momentary-assessment (EMA) design will be used to collect data on sleep and emotions (diaries), sleep-wake parameters (actigraphy) and stress reactivity (salivary cortisol). We will also test the DNA methylation of genes involved in the stress response as biomarkers of prenatal poor sleep. Information on partner’s insomnia symptoms and new-borns’ sleep will be collected at each stage. Discussion The proposed protocol aims at testing an easily accessible evidence-based psychoeducational intervention for expectant mothers to help them improving sleep, health, and wellbeing in the peripartum. The results could improve the understanding and management of sleep difficulties and peripartum depression. Trial registration The study protocol has been registered on 22 April 2024 with ClinicalTrials.gov Protocol Registration and Results System (PRS), ID: NCT06379074. Protocol version: April 23, 2024.

Abstract Biostimulants are heterogeneous products designed to support plant development and to improve the yield and quality of crops. Here, we focused on the effects of triacontanol, a promising biostimulant found in cuticle waxes, on tomato growth and productivity. We examined various phenological traits related to vegetative growth, flowering and fruit yield, the metabolic profile of fruits, and the response of triacontanol-treated plants to salt stress. Additionally, a proteomic analysis was conducted to clarify the molecular mechanisms underlying triacontanol action. Triacontanol application induced advanced and increased blooming without affecting plant growth. Biochemical analyses of fruits showed minimal changes in nutritional properties. The treatment also increased the germination rate of seeds by altering hormone homeostasis and reduced salt stress-induced damage. Proteomics analysis of leaves revealed that triacontanol increased the abundance of proteins related to development and abiotic stress, while down-regulating proteins involved in biotic stress resistance. The proteome of the fruits was not significantly affected by triacontanol, confirming that biostimulation did not alter the nutritional properties of fruits. Overall, our findings provide evidence of the effects of triacontanol on growth, development, and stress tolerance, shedding light on its mechanism of action and providing new insights into its potential in agricultural practices.

Abstract Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright–Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte’s structural integrity. Maximum loading achieved (1386.68 ± 22.43 μg/ml) at 1500 μg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1β, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.

En la vida y obra da Gamaliel Churata la muerte de su esposa Brunilda (Rosa Calderón) y de sus hijos Teófano (Teófano Peralta) y Qimensa (Clemencia Peralta) tuvo un impacto singular. Este acontecimiento no solo afectó a Churata, sino que también alcanzó a otros miembros del Grupo Orkopata, quienes escribieron poemas dedicados a estas almas significativas. En este artículo estudiamos el ritual de la muerte representado en la poesía de Churata, en específico a las fases que corresponden a la partida y al retorno del alma (ajayu). Para ello, analizamos dos poemas dedicados a la muerte de Teófano, que siguen esta secuencia ritual. Nos serán de utilidad las categorías de ajayu, amaya y ajayu-watan, además de las nociones de la lírica andina. Con ello, evidenciaremos que el canto a la muerte propuesto por Churata sigue el ritual de la concepción andina de la muerte, en especial el ritual aymara.

Neste artigo propõe-se analisar os discursos produzidos sobre as bruxas, mulheres e feminino, contidos no tratado de Demonologia, Malleus Maleficarum (Martelo das Bruxas) escrito no período inquisitorial. Através de fragmentos do tratado é possível perceber a produção de lugares destinados ao feminino e às mulheres. Por meio da análise do discurso, e nos pressupostos foucaultianos, põe-se também em evidência a teia de relações e técnicas de saber e poder que envolvem as mulheres, a bruxaria e o feminino. Finalmente, compreendendo que linguagem e discurso são lugares de lutas e disputas permanentes, constata-se a reverberação dos discursos originados no período histórico inquisitorial até os dias atuais.

Hypertensive crises in pediatric patients are rare conditions. However, determining their precise prevalence is more challenging than in adults due to the heterogeneity in the definition itself. These crises frequently occur without a prior diagnosis of hypertension and may indicate an underlying cause of secondary hypertension, including pheochromocytoma/paraganglioma (PPGL). The mechanisms of hypertensive crises in the pediatric population with PPGL are directly related to different types of catecholamine excess. Noradrenergic tumors typically present with sustained hypertension due to their predominant action on α1-adrenoceptors in the vasculature. Conversely, adrenergic tumors, through epinephrine binding to β2-adrenoceptors in addition to stimulation of α1- and α2-adrenoceptors, more frequently cause paroxysmal hypertension. Furthermore, the biochemical phenotype also reflects the tumor localization and the presence of a genetic mutation. Recent evidence suggests that more than 80% of PPGL in pediatric cases have a hereditary background. PPGL susceptibility mutations are categorized into three clusters; mutations in cluster 1 are more frequently associated with a noradrenergic phenotype, whereas those in cluster 2 are associated with an adrenergic phenotype. Consequently, the treatment of hypertensive crises in pediatric patients with PPGL, reflecting the underlying pathophysiology, requires first-line therapy with alpha-blockers, potentially in combination with beta-blockers only in the case of tachyarrhythmia after adequate alpha-blockade. The route of administration for treatment depends on the context, such as intraoperative or pre-surgical settings, and whether it presents as a hypertensive emergency (elevated blood pressure with acute target organ damage), where intravenous administration of antihypertensive drugs is mandatory. Conversely, in cases of hypertensive urgency, if children can tolerate oral therapy, intravenous administration may initially be avoided. However, managing these cases is complex and requires careful consideration of the selection and timing of therapy administration, particularly in pediatric patients. Therefore, facing these conditions in tertiary care centers through interdisciplinary collaboration is advisable to optimize therapeutic outcomes.

BackgroundSevere eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short- and middle-term effects are well described, no study has so far investigated its long-lasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients.MethodsWe conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20).ResultsOf 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment.ConclusionMepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function.

This work provides an investigation of the influence of low temperature heat treatments on the fatigue behavior of a PBF-LB AlSi10Mg alloy. Fatigue specimens are produced in form of round bars on a build platform preheated at 200 °C. The specimens have been tested in three different conditions: as-built, and after heat treatments at 265 °C for 1 h and 300 °C for 2 h. Prior to the fatigue testing, the defect distribution is analyzed by means of micro computed tomography. Subsequently, the peak over threshold method is successfully applied to provide a prediction of the size of killer defect. The defect population was of gas porosity type. No clear improvement of the fatigue performance is observed after the heat treatments. The fatigue strength predicted using fracture mechanics-based approaches is in good agreement with the experimental data. Among the studied approaches, short crack models provided the most conservative predictions.

IntroductionSARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.MethodsWe longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.ResultsMore than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14+CD91+ monocytes, and high CD8+ Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.DiscussionThese results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.

IntroductionPreclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents.MethodsThe in vitro pharmacology of RG7774 was investigated for CB2R binding and receptor activation using recombinant human and mouse CB2R expression in Chinese hamster ovary cells, and endogenous CB2R expression in human Jurkat cells, and rat and mouse spleen cells. The ADMET profile was evaluated and the effects of RG7774 on retinal permeability, leukocyte adhesion, and choroidal neovascularization (CNV) were investigated in rodent models of retinal disease. Pharmacokinetic (PK) parameters and the exposure-response relationship were characterized in healthy animals and in animals with laser-induced CNV.ResultsRG7774 was found to be a potent (EC50: 2.8 nM and Ki: 51.3 nM), selective, and full CB2R agonist with no signs of cannabinoid receptor type 1 (CB1R) binding or activation. The ligand showed a favorable ADMET profile and exhibited systemic and ocular exposure after oral delivery. Functional potency in vitro translated from recombinant to endogenous expression systems. In vivo, orally administered RG7774 reduced retinal permeability and leukocyte adhesion in rodents with lipopolysaccharide (LPS)-induced uveitis and streptozotocin (STZ)-induced DR, and reduced lesion areas in rats with laser-induced CNV with an ED50 of 0.32 mg/kg. Anatomically, RG7774 reduced the migration of retinal microglia to retinal lesions.DiscussionRG7774 is a novel, highly selective, and orally bioavailable CB2R agonist, with an acceptable systemic and ocular PK profile, and beneficial effects on retinal vascular permeability, leukocyte adhesion, and ocular inflammation in rodent animal models. Results support the development of RG7774 as a potential treatment for retinal diseases with similar pathophysiologies as addressed by the animal models.

Resumo: A versão de sentido foi desenvolvida há mais de vinte anos como instrumento de registro e reflexão na prática psicoterápica. Trata-se de um modo breve de registrar a experiência essencial de uma sessão, diferentemente do costumeiro e longo relatório. Desde a sua origem, o uso da versão de sentido tem se espalhado por várias regiões do Brasil, tanto na clínica quanto na academia. Esta revisão integrativa tem como objetivo verificar a evolução do conceito de versão de sentido desde a sua concepção até os dias atuais e em quais contextos é utilizada. Os 29 trabalhos selecionados revelam que a versão de sentido vem sendo usada em diversos contextos, com uma variedade de procedimentos e caracterizações que, no entanto, não eliminam a intenção comum de facilitar o acesso ao sentido vivido pelos participantes do encontro.

Microplastics (MP) can influence a plethora of fungal species within the rhizosphere. Nevertheless, there are few studies on the direct impacts of MPs on soil fungi and their intricate interplay with plants. Here, we investigated the impact of polyethylene microspheres (PEMS) on the ecological interactions between Fusarium solani, a plant pathogenic fungus, and Trichoderma viride, a fungal plant growth promotor, within the rhizosphere of Solanum lycopersicum (tomato). Spores of F. solani and T. viride were pre-incubated with PEMS at two concentrations, 100 and 1000 mg L-1. Mycelium growth, sporulation, spore germination, and elongation were evaluated. Tomato seeds were exposed to fungal spore suspensions treated with PEMS, and plant development was subsequently assessed after 4 days. The results showed that PEMS significantly enhanced the sporulation (106.0 % and 70.1 %) but compromised the spore germination (up to 27.3 % and 32.2 %) and radial growth (up to -5.2% and -21.7 %) of F. solani and T. viride, respectively. Furthermore, the 100 and 1000 mg L-1 concentrations of PEMS significantly (p

Abstract The media and even the specialized literature report that the ultraviolet (UV) protection for sunglasses is critical, on the grounds that sunglasses can have a counter effect if the lenses do not provide adequate UV protection. They reason that the primary and natural mechanism is that the pupil of the eye contracts to attenuate radiation and protect the inner eye under sun exposure. Therefore, if dark lenses do not provide appropriate UV protection, there is an increased UV incidence in the inner eye due to pupil dilation, which enhances the adverse effects and impacts the ocular tissues more severely than in situations without UV protection. However, no existing literature properly quantified or supported this argument. In this work, the influx of solar UV throughout the pupil of the eye was calculated in two situations: when a person wear sunglasses and when he/she does not. In both situations, the pupil dilation and the field of view (squint) were considered with their dependence on the brightness of the ambient, calculated by modeling the solar irradiation. Finally, it was assessed whether sunglasses with poor UV protection actually increase the UV influx throughout the dilated pupil compared to the non-dilated pupil. A set of 214 sunglasses lenses were tested and the results show that pupil dilation does not play an important role in the UV influx throughout the pupil. It was observed that the FOV is the main player, surpassing the pupil size contribution by up to 314.3%, disproving the common explanation. Because of the major role of the FOV, our results show that sunglasses with UV-A protection below 86% may have a slight potential to increase hazards to the eye compared to not wearing sunglasses at all. These results can have direct impact on sunglasses standards regarding the UV protection linked to the category of the lenses.

Abstract Background Severe asthma can cause poor health status, poor health-related quality of life (HRQoL) and an impaired functioning at work. However, to date, limited data are available on the impact of the biological therapies on such outcomes. Therefore, aim of the present study was to prospectively assess the clinical, quality of life and work functionality issues in severe asthma patients both at baseline and after 6 months of biological therapies and determine which individual, pathological and occupational factors can influence such parameters. Methods Fifty-two patients were enrolled between December 2022 and June 2023. Patients’ personal, clinical, functional and occupational features were assessed. The Short Form Health Survey (SF-12), the Work Productivity and Activity Impairment (WPAI) questionnaire and the Work Ability Index (WAI) were employed to assess HRQoL, the employee’s productivity and perception of work ability, respectively. Results Among the enrolled patients, 30 (57.70%) were employed. Biological therapy induced a significant improvement in clinical and functional parameters, e.g., FEV1% (72 ± 12 vs.87 ± 13%; 72 ± 14 vs. 86 ± 14%), FVC% (92 ± 11 vs. 101 ± 11%; 90 ± 13 vs. 98 ± 14%) and FEV1/FVC (62 ± 11 vs. 71 ± 8%; 64 ± 9 vs. 70 ± 8%) in workers and non-workers, respectively (P

Understanding and monitoring the surrounding environment increasingly rely on its 3-D representations. However, the often high costs of 3-D data equipment limit its wide usage, and low-cost solutions are in demand. Here, we propose a novel approach based on spherical stereo videos captured with a known baseline (distance between the cameras) for a low-cost and efficient 3-D point cloud reconstruction. In a forest environment, we evaluated 1) the influence of baseline length on point cloud quality and 2) the suitability of the generated point clouds for extracting primary forest attributes (tree position and diameter). Our results show that the proposed approach allows for feasible 3-D reconstruction of complex forest plots. The highest point cloud quality was achieved with a baseline of 60 cm. This setup enabled the correct detection of more than 65% of the trees within the forest plots, producing an average tree position error between 30 and 50 cm and clearly outperforming other setups. A multiscale model-to-model cloud comparison analysis showed signed distances between the generated point cloud and the reference data with zero mean and 1 m standard deviation. We demonstrate that the proposed approach can be a valuable low-cost solution for 3-D point cloud reconstruction, facilitating forest assessment and monitoring.

Expensive sensors and inefficient algorithmic pipelines significantly affect the overall cost of autonomous machines. However, affordable robotic solutions are essential to practical usage, and their financial impact constitutes a fundamental requirement for employing service robotics in most fields of application. Among all, researchers in the precision agriculture domain strive to devise robust and cost-effective autonomous platforms in order to provide genuinely large-scale competitive solutions. In this article, we present a complete algorithmic pipeline for row-based crops autonomous navigation, specifically designed to cope with low-range sensors and seasonal variations. Firstly, we build on a robust data-driven methodology to generate a viable path for the autonomous machine, covering the full extension of the crop with only the occupancy grid map information of the field. Moreover, our solution leverages on latest advancement of deep learning optimization techniques and synthetic generation of data to provide an affordable solution that efficiently tackles the well-known Global Navigation Satellite System unreliability and degradation due to vegetation growing inside rows. Extensive experimentation and simulations against computer-generated environments and real-world crops demonstrated the robustness and intrinsic generalizability to different factors of variations of our methodology that open the possibility of highly affordable and fully autonomous machines.

Abstract A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.

Globally positive unbounded solutions, with zero derivative at infinity, are here considered for ordinary differential equations involving the generalized Euclidean mean curvature operator. When p≥2, the results highlight an analogy with an auxiliary equation with the p-Laplacian operator. The results are obtained using some comparison criteria for the principal solutions of a class of associated half-linear equations.

This research investigates the dynamics of contaminant exposure in European hake (Merluccius merluccius, L. 1758) from the Adriatic Sea (Central Mediterranean Sea) by examining the levels of total mercury (THg) and polycyclic aromatic hydrocarbons (PAHs) in the muscle fish tissues. The study explores the correlations between these pollutants and somatic indexes to identify the early warning signals of pollution and ecological effects. The levels of pollutants are influenced by season and sex. Lipids appear to have a minimal effect on the PAH levels, whereas they exhibit a positive correlation with mercury levels in the muscle. No significant relationships between the pollutants and condition indexes were observed, except for a positive correlation between THg and the gonadosomatic index, indicating a potential impact on the reproductive health of fish. In contrast, PAHs showed no meaningful correlation with condition indexes. Differences in contaminant accumulations and lipid levels between sexes reflect variations in metabolic activity, reproductive costs, and adaptive strategies to seasonal changes and energy demands. This study highlights the importance of long-term monitoring to improve pollution management, environmental conservation, and the protection of marine organisms’ health.

Survivors of neurologic injury (most commonly stroke or traumatic brain injury) frequently experience a disorder in which contralesionally positioned objects or the contralesional features of individual objects are often left unattended or underappreciated. The disorder is known by >200 unique labels in the literature, which potentially causes confusion for patients and their families, complicates literature searches for researchers and clinicians, and promotes a fractionated conceptualization of the disorder. The objective of this Delphi was to determine if consensus (≥75% agreement) could be reached by an international and multidisciplinary panel of researchers and clinicians with expertise on the topic.To accomplish this aim, we used a modified Delphi method in which 66 researchers and/or clinicians with expertise on the topic completed at least 1 of 4 iterative rounds of surveys. Per the Delphi method, panelists were provided with results from each round prior to responding to the survey in the subsequent round with the explicit intention of achieving consensus. The panel ultimately reached consensus that the disorder should be consistently labeled spatial neglect. Based on the consensus reached by our expert panel, we recommend that researchers and clinicians use the label spatial neglect when describing the disorder in general and more specific labels pertaining to subtypes of the disorder when appropriate.