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Non-thermal plasma (NTP) shows promise as a potent anti-cancer therapy with both cytotoxic and immunomodulatory effects. In this study, we investigate the chemical and biological effects of NTP-induced oxidation on several key, determinant immune checkpoints of natural killer (NK) cell function. We used molecular dynamics (MD) and umbrella sampling simulations to investigate the effect of NTP-induced oxidative changes on the MHC-I complexes HLA-Cw4 and HLA-E. Our simulations indicate that these chemical alterations do not significantly affect the binding affinity of these markers to their corresponding NK cell receptor, which is supported with experimental read-outs of ligand expression on human head and neck squamous cell carcinoma cells after NTP application. Broadening our scope to other key ligands for NK cell reactivity, we demonstrate rapid reduction in CD155 and CD112, target ligands of the inhibitory TIGIT axis, and in immune checkpoint CD73 immediately after treatment. Besides these transient chemical alterations, the reactive species in NTP cause a cascade of downstream cellular reactions. This is underlined by the upregulation of the stress proteins MICA/B, potent ligands for NK cell activation, 24 h post treatment. Taken together, this work corroborates the immunomodulatory potential of NTP, and sheds light on the interaction mechanisms between NTP and cancer cells.

IntroductionImmune dysregulation plays a major role in cancer progression. The quantification of lymphocytic spatial inflammation may enable spatial system biology, improve understanding of therapeutic resistance, and contribute to prognostic imaging biomarkers.MethodsIn this paper, we propose a knowledge-guided deep learning framework to measure the lymphocytic spatial architecture on human H&E tissue, where the fidelity of training labels is maximized through single-cell resolution image registration of H&E to IHC. We demonstrate that such an approach enables pixel-perfect ground-truth labeling of lymphocytes on H&E as measured by IHC. We then experimentally validate our technique in a genetically engineered, immune-compromised Rag2 mouse model, where Rag2 knockout mice lacking mature lymphocytes are used as a negative experimental control. Such experimental validation moves beyond the classical statistical testing of deep learning models and demonstrates feasibility of more rigorous validation strategies that integrate computational science and basic science.ResultsUsing our developed approach, we automatically annotated more than 111,000 human nuclei (45,611 CD3/CD20 positive lymphocytes) on H&E images to develop our model, which achieved an AUC of 0.78 and 0.71 on internal hold-out testing data and external testing on an independent dataset, respectively. As a measure of the global spatial architecture of the lymphocytic microenvironment, the average structural similarity between predicted lymphocytic density maps and ground truth lymphocytic density maps was 0.86 ± 0.06 on testing data. On experimental mouse model validation, we measured a lymphocytic density of 96.5 ± %1% in a Rag2+/- control mouse, compared to an average of 16.2 ± %5% in Rag2-/- immune knockout mice (p

Rural areas are regaining attention as key resource holders. This includes the attractiveness of intact and traditional cultural elements and heritage which helps to create new opportunities. However, renewal is needed for rural areas to be competitive beyond tourism. Knowledge exchange and transfer is seen as an enabling tool for regeneration and heritage valorization, although it has mostly been applied in an urban context. The aim of this paper is to explore the role of capacity building and knowledge exchange at different levels in promoting rural regeneration through heritage-led initiatives. The article describes a multi-directional knowledge transfer and exchange in 19 rural areas. The applied knowledge exchange methodology was designed to be a dynamic and vibrant exchange of capacity building and mutual learning. This exchange of knowledge enabled the local communities involved to explore new ideas and viable solutions for the regeneration of rural areas through the valorization of cultural and natural heritage. The research findings show that structuring a knowledge transfer and capacity building process that also involves key local stakeholders and the rural communities is an important milestone in the regeneration process. In addition, it can be a unique opportunity to start and build new professional long-term relationships.

Introduction: Immune dysregulation plays a major role in cancer progression. The quantification of lymphocytic spatial inflammation may enable spatial system biology, improve understanding of therapeutic resistance, and contribute to prognostic imaging biomarkers. Methods: In this paper, we propose a knowledge-guided deep learning framework to measure the lymphocytic spatial architecture on human H&E tissue, where the fidelity of training labels is maximized through single-cell resolution image registration of H&E to IHC. We demonstrate that such an approach enables pixel-perfect ground-truth labeling of lymphocytes on H&E as measured by IHC. We then experimentally validate our technique in a genetically engineered, immune-compromised Rag2 mouse model, where Rag2 knockout mice lacking mature lymphocytes are used as a negative experimental control. Such experimental validation moves beyond the classical statistical testing of deep learning models and demonstrates feasibility of more rigorous validation strategies that integrate computational science and basic science. Results: Using our developed approach, we automatically annotated more than 111,000 human nuclei (45,611 CD3/CD20 positive lymphocytes) on H&E images to develop our model, which achieved an AUC of 0.78 and 0.71 on internal hold-out testing data and external testing on an independent dataset, respectively. As a measure of the global spatial architecture of the lymphocytic microenvironment, the average structural similarity between predicted lymphocytic density maps and ground truth lymphocytic density maps was 0.86 ± 0.06 on testing data. On experimental mouse model validation, we measured a lymphocytic density of 96.5 ± %1% in a Rag2+/- control mouse, compared to an average of 16.2 ± %5% in Rag2-/- immune knockout mice (p<0.0001, ANOVA-test). Discussion: These results demonstrate that CD3/CD20 positive lymphocytes can be accurately detected and characterized on H&E by deep learning and generalized across species. Collectively, these data suggest that our understanding of complex biological systems may benefit from computationally-derived spatial analysis, as well as integration of computational science and basic science. [ABSTRACT FROM AUTHOR]

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD–specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD. [ABSTRACT FROM AUTHOR]

A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Objectives: Decision‐making for patients with a locally advanced laryngeal carcinoma (T3 and T4) is challenging due to the treatment choice between organ preservation and laryngectomy, both with different and high impact on function and quality of life (QoL). The complexity of these treatment decisions and their possible consequences might lead to decisional conflict (DC). This study aimed to explore the level of DC in locally advanced laryngeal carcinoma patients facing curative decision‐making, and to identify possible associated factors. Methods: In this multicenter prospective cohort study, participants completed questionnaires on DC, level of shared decision‐making (SDM), and a knowledge test directly after counseling and 6 months after treatment. Descriptive statistics and Spearman correlation tests were used to analyze the data. Results: Directly after counseling, almost all participants (44/45; 98%) experienced Clinically Significant DC score (CSDC >25, scale 0–100). On average, patients scored 47% (SD 20%) correct on the knowledge test. Questions related to radiotherapy were answered best (69%, SD 29%), whilst only 35% (SD 29%) of the questions related to laryngectomy were answered correctly. Patients' perceived level of SDM (scale 0–100) was 70 (mean, SD 16.2), and for physicians this was 70 (SD 1.7). Conclusion: Most patients with advanced larynx cancer experience high levels of DC. Low knowledge levels regarding treatment aspects indicate a need for better patient counseling. Level of Evidence: 4 Laryngoscope, 134:3604–3610, 2024 [ABSTRACT FROM AUTHOR]

Importance: Head and neck cancer (HNC) often requires treatment with a major impact on quality of life. Treatment decision-making is often challenging, as it involves balancing survival against the preservation of quality of life and choosing among treatments with comparable outcomes but variation in morbidity and adverse events; consequently, the potential for decisional conflict (DC) and decision regret (DR) is high., Objectives: To summarize the literature on DC and DR in HNC, to give an overview of its prevalence and extent, and to advise on clinical practice and future research., Data Sources: Embase, Web of Science, MEDLINE, and PsycINFO were searched up to February 24, 2023, including all years of publication., Study Selection: Eligible studies addressed DC and/or DR as primary or secondary outcomes with any instrument in HNC, except cutaneous tumors. Two mutually blinded researchers conducted screening and inclusion with support of an artificial intelligence assistant and conducted risk of bias (ROB) assessment., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed for data extraction. ROB assessments were done using Critical Appraisal Skills Programme (qualitative) and CLARITY (quantitative). Meta-analysis with a random-effects model was used to obtain pooled prevalence estimates for DC and DR when at least 4 sufficiently clinically homogeneous studies were available., Main Outcomes and Measures: Prevalence of DC (qualitative, Decisional Conflict Scale, SURE questionnaire) and DR (qualitative, study-specific questionnaires, Decision Regret Scale, Shame and Stigma Scale)., Results: Overall, 28 studies were included, with 16 included in meta-analyses for DR prevalence. The pooled prevalence of clinically relevant DR above the cutoff score for validated questionnaires (11 studies; 2053 participants) was 71% (95% CI, 58%-82%; I2 = 94%), while for study-specific questionnaires (5 studies; 674 participants) it was 11% (95% CI, 5%-22%; I2 = 92%). Only 4 studies investigated DC, showing a prevalence of 22.6% to 47.5% above cutoff values. Derived overarching themes found in qualitative studies were preparation, shared decision-making roles, information, time pressure, stress of diagnosis, and consequences., Conclusions and Relevance: Although limited data on DC and DR were available, the studies performed indicated that DC and DR are highly prevalent issues in HNC. Results suggest that study-specific questionnaires underestimated DR. The findings underscore the rationale to improve counseling and shared decision-making for this patient population.

Objective: After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. Methods: Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded. Results: All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. Conclusion: Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample. [ABSTRACT FROM AUTHOR]

Magnetic field-assistance holds the promise of becoming a new or complementary approach to enhance the efficiency of atmospheric pressure plasma jet (APPJ), but there is currently a lack of research on the effect of the assistance region between magnetic field and plasma on application of APPJ. Herein, using a 130 mT perpendicular magnetic field to assist APPJ in treating deionized water to prepare plasma activated water (PAW) as a model, we studied the effect of the magnetic field-assisted region on the performance of PAW produced by APPJ, and found that introducing a magnetic field could always enhance the performance of the prepared PAW with higher concentrations of H2O2, NO3-, and NO2- and lower concentrations of O3 and lower pH values, but this enhancement effect was related to the magnetic field-assisted region relative to the APPJ, where the optimized PAW performance was achieved when the magnetic field did not act on the jet tube wall (only assisting plasma plume). To reveal the underlying physicochemical mechanism behind the differences in the enhanced performance of PAW in different magnetic field-assisted regions, a plasma reaction network involving physical parameters and chemical products was considered. The results showed that the magnetic field-assisted region modulated the equilibrium between the confinement effect and the recombination loss of magnetized electrons, and subsequently altered the reactive species in PAW via a plasma reaction network mediated by electron density ne and electron excitation temperature Texc without remarkably changing the discharge intensity, discharge power, plasma plume, and gas temperature Tgas. These insights contribute to understanding the mechanism of the magnetic fieldassisted region effect on APPJ, which provides guidance for optimizing discharge activity and promotes the development of applications. [ABSTRACT FROM AUTHOR]

The advent of RNA therapy, particularly through the development of mRNA cancer vaccines, has ushered in a new era in the field of oncology. This article provides a concise overview of the key principles, recent advancements, and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment. mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body's innate immune system. These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens, prompting the immune system to recognize and mount a targeted response against malignant cells. This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients. Recent breakthroughs in the development of mRNA vaccines, exemplified by the success of COVID-19 vaccines, have accelerated their application in oncology. The mRNA platform's versatility allows for the rapid adaptation of vaccine candidates to various cancer types, presenting an agile and promising avenue for therapeutic intervention. Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety, immunogenicity, and efficacy. Pioneering candidates, such as BioNTech's BNT111 and Moderna's mRNA-4157, have exhibited promising outcomes in targeting melanoma and solid tumors, respectively. These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses. While the field holds great promise, challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption. The development of scalable and cost-effective manufacturing processes, along with ongoing clinical research, will be pivotal in realizing the full potential of mRNA cancer vaccines. Overall, mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment. As research progresses, addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice, offering new hope for patients in the fight against cancer. [ABSTRACT FROM AUTHOR]

Purpose: The negative effects of job stress and burnout on construction professionals (CPs) at the construction site have been widely concern in the construction industry. The purpose of this study is committed to explore the impact of job stress on CPs on the construction site, especially in the context of the widespread use of social media to express their emotions. Design/methodology/approach: This study developed a job-related stress-burnout-health conditions-turnover intention (S-B-HT) framework to explore the direct and lagged effects of job stress, we also examined the moderating effects of online emotions, operationalized in terms of emotional intensity and expression pattern, on the relationship between job stress with job burnout under two evolution paths (i.e. health conditions or turnover intention). This study collected 271 samples through a survey questionnaire for empirical testing, and introduced structural equation models to validate the proposed conceptual model. Findings: The results show that job stress has a significant positive effect on job burnout, and job burnout maintains a positive relationship with health conditions (or turnover intention) under the interference mechanism. Simultaneously, the online emotions expressed in social media have a positive moderating effect in two stages of the evolution path. Practical implications: The findings of this study remind the project manager need to timely find and solve the job burnout characteristics of CPs due to excessive job stress, especially to prevent the accidental consequences caused by job burnout. Originality/value: On this basis, this study provides an important value of using social media to express emotions for the project team to alleviate the adverse of professionals under job stress. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 Omicron sublineages escape most preclinical/clinical neutralizing antibodies in development, suggesting that previously employed antibody screening strategies are not well suited to counteract the rapid mutation of SARS‐CoV‐2. Therefore, there is an urgent need to screen better broad‐spectrum neutralizing antibody. In this study, a comprehensive approach to design broad‐spectrum inhibitors against both SARS‐CoV‐1 and SARS‐CoV‐2 by leveraging the structural diversity of nanobodies is proposed. This includes the de novo design of a fully human nanobody library and the camel immunization‐based nanobody library, both targeting conserved epitopes, as well as the development of multivalent nanobodies that bind nonoverlapping epitopes. The results show that trivale B11‐E8‐F3, three nanobodies joined tandemly in trivalent form, have the broadest spectrum and efficient neutralization activity, which spans from SARS‐CoV‐1 to SARS‐CoV‐2 variants. It is also demonstrated that B11‐E8‐F3 has a very prominent preventive and some therapeutic effect in animal models of three authentic viruses. Therefore, B11‐E8‐F3 has an outstanding advantage in preventing SARS‐CoV‐1/SARS‐CoV‐2 infections, especially in immunocompromised populations or elderly people with high‐risk comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: From the observation of a negative relationship between UV-B exposure and cancer rates, we hypothesized that vitamin D (VD) may play a protective role in oncogenesis. Moreover, repurposing a well-known and relatively safe drug for conditions with dismal prospects, such as pancreatic ductal adenocarcinoma (PDAC), is a tempting idea. Thus, we aimed to summarize the current knowledge regarding the role of VD in the prevention and treatment of PDAC. Methods: We conducted a systematic review of VD and PDAC using Medline-indexed studies accessed through PubMed as the primary data source. This study aimed to identify articles focusing on the role of VD as a risk and prognostic factor for PDAC, mechanistic studies evaluating the effects of VD or vitamin D analogs (VDAs) in PDAC models, and clinical trials on VDAs in PDAC. After the screening, 97 studies were included in the final manuscript. Conclusion: Even though the results from epidemiologic studies were contradictory, basic research has demonstrated that VD can act on PDAC cells either directly, inhibiting proliferation, apoptosis, EMT, migration, invasion, and stemness, or indirectly, through stromal remodeling. A better understanding of the consequences of VD-induced tumor–stroma cross-talk alterations is needed to determine whether VD/VDAs can be used to our own advantage in the treatment of PDAC. [ABSTRACT FROM AUTHOR]

Outlined is a proposal designed to culminate in the foundry fabrication of arrays of singly addressable quantum dot sources deterministically emitting single pairs of energy-time entangled photons at C-band wavelengths, each pair having negligible spin-orbit fine structure splitting, each pair being channeled into single mode pig-tail optical fibers. Entangled photons carry quantum state information among distributed quantum servers via I/O ports having two functions: the unconditionally secure distribution of decryption keys to decrypt publicly distributed, encrypted classical bit streams as input to generate corresponding qubit excitations and to convert a stream of quantum nondemolition measurements of qubit states into a classical bit stream. Outlined are key steps necessary to fabricate arrays of on-demand quantum dot sources of entangled photon pairs; the principles are (1) foundry fabrication of arrays of isolated quantum dots, (2) generation of localized sub-surface shear strain in a semiconductor stack, (3) a cryogenic anvil cell, (4) channeling entangled photons into single-mode optical fibers, (5) unconditionally secure decryption key distribution over the fiber network, (6) resonant excitation of a Josephson tunnel junction qubits from classical bits, and (7) conversion of quantum nondemolition measurements of qubit states into a classical bit. [ABSTRACT FROM AUTHOR]

Background: CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear. Aim: To explore the relationship between CD83 and CD4+ T cell subsets and clarify the role of CD83 in the pathogenesis of ITP. Methods: RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4+ T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression. Results: The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4+ T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-β, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression. Conclusion: The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients. [ABSTRACT FROM AUTHOR]

Introduction: Unwanted exposure (UE) to sexual content may have important consequences on children/adolescents' psychosexual development. Our objective was to analyze UE to online pornography, parental filter use, type of sexual contents seen, emotional/behavioral reactions, and UE as positive/traumatic experience in Spanish adolescents and to examine these experiences and reactions depending on the type of sexual content. Methods: In 2020, 500 Spanish teenagers (13–18 years) completed an ad hoc questionnaire for the evaluation of different dimensions involved in UE to sexual contents, such as those mentioned in the study objectives. Results: A high frequency of UE (88.2%) is observed. Regarding the kind of scenes, naked people, straight porn, and people showing genitals are the most unexpectedly seen. Adolescents used to react to the UE closing the window and deleting sexual materials. A greater predominance of negative emotions was revealed, and another noteworthy result is related to the role played by type of sexual content and gender. Gay scenes and being woman increased the probability of living the experience as non-positive, and being woman and viewing naked people/BDSM scenes/under-age sex were associated with reactions of rejection. Conclusions: This study contributes significantly to the knowledge of UE to online pornography in adolescents. It provides valuable information about the role played by the type of sexual content seen and the gender in the diverse reactions/experiences derived from the UE to pornography. Policy Implications: This topic, that is, involuntary exposure to online sexual material in adolescents, should be included in affective-sexual education and prevention programs at early ages, so that children/adolescents are already trained in healthy sexuality when facing this type of content for the first time. These programs, adjusted to the reality of our adolescents, will minimize the negative impact that UE may have on their psychosexual development. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this paper is to advance research concerning the factors affecting the intentions to start-up. In this vein, scholars are more and more interested in perceptual variables, i.e. subjective perceptions that may affect individuals' intentions to start-up. These can have an internal locus of control (PVIs), if they depend on personal cognitive styles, or an external locus of control (PVEs), if they depend on how individuals perceive environmental stimuli. Usually, scholars investigate them at a micro-level of analysis, by focusing on individuals in a country. Instead, this paper adopts a macro-level analysis. Thus, the research question at the basis of this paper is: whether the impact of perceptual variables (with an internal or external locus of control) on the intentions to start-up varies across countries. Design/methodology/approach: Stochastic frontier analyses – SFAs are carried out since they allow disentangling technical and random inefficiencies and comparing statistical results. SFAs are based on data retrieved from the Global Entrepreneurship Monitor – GEM website and refer to PIGS (Portugal, Italy, Greece, and Spain) and BRICs (Brazil, Russia, India, and China) countries where entrepreneurship is a vibrant phenomenon, but cultural and economic differences are manifest. Findings: Concerning the drivers of entrepreneurship, achieved results reveal that some differences exist across PIGS and BRICs countries, but they cannot be generalized so easily. Originality/value: This paper reveals its originality in reference to the classification of the variables, the macro-level of analysis, and the results that – at the same time – are in line with previous ones, but also offer new insights about perceptual variables in entrepreneurship and – at a wider extent – about the drivers of entrepreneurship. [ABSTRACT FROM AUTHOR]

The integration of electrospun nanofibres into composite materials such as carbon fibre reinforced polymers (CFRP) and glass fibre reinforced polymers (GFRPs) has gained significant attention for enhancing their mechanical and thermal properties. This study focuses on the impact of incorporating polyacrylonitrile (PAN)-based nanofibres into an epoxy matrix to form multi-layered laminate composites. Our approach involved interleaving these orientated nanofibres within CFRP/GFRP matrices to investigate improvements in bulk material characteristics. The tensile and thermal properties of the resulting nanocomposites were thoroughly analysed. Thermogravimetric analysis (TGA) was employed to evaluate the thermal stability and degradation behaviour. In particular, nanocomposites exhibited an increase of 5–24 % in elastic modulus, aligning with predictions from analytical models. This research underscores the potential of PAN nanofibre mats for the development of lightweight, high-performance nanocomposites, offering a novel methodology for the enhancement of composite materials. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is exploring teenagers' (aged 11–17) and their parents' reflections and insights regarding influencer marketing on social media, with a particular focus on advertising literacy and associated ethical perspectives. It examines the impact of influencer marketing on teenagers' decision-making processes and emphasizes the importance of influencers clearly indicating their advertising collaborations. The study delves into the ethical aspects of advertising literacy, highlighting the significant role that transparent signaling of commercial collaborations plays. Design/methodology/approach: The research involved conducting 40 interviews with both teenagers and one of their parents. Findings: The study highlights a divergence in perspectives between teenagers and their parents regarding influencer marketing. While parents emphasized the importance of influencers clearly disclosing the commercial nature of sponsored content, teenagers did not see this as necessary. Additionally, the study found that parents often overlooked the ethical implications of honesty in influencer marketing discussions. Originality/value: These findings underscore the importance of further exploring the complexities surrounding influencer marketing dynamics and the crucial role that parents can play in promoting ethical advertising literacy among teenagers. [ABSTRACT FROM AUTHOR]

Subaqueous mass transport deposits (MTDs) attributed to the Mw 6.1 1935 CE Témiscaming earthquake were mapped at 17 sub-bottom acoustic profile survey areas on 11 lakes near Témiscaming, Quebec. Distributed over about 1270 km2, MTDs are the product of shallow failures, up to several metres thick, that occurred along planar surfaces and involved primarily lacustrine sediments. Core samples of unfailed deposits indicate that the failure planes occurred within soft sediments at the top of a glaciolacustrine unit or at the base of overlying lacustrine deposits. Radioisotope dating of sediment samples from six coring sites on Tee and Kipawa lakes confirm that the MTDs are the product of failures triggered by the 1935 CE earthquake. To assess the application of such a mapping study to a paleoseismic investigation, the minimum magnitude of an earthquake that can generate an MTD distribution of 1270 km2 was extrapolated from a published empirical plot. The resulting magnitude of Mw/Ms 5.7–5.8 is less than the instrumental Mw 6.1 magnitude and deemed a reasonable estimation of minimum earthquake magnitude. The distribution of MTDs triggered by the 1935 CE earthquake forms the only such signature within the Témiscaming study area since roughly 8 ka cal B.P. The lack of an analogous, older signature(s) is consistent with the absence of equivalent shaking to the 1935 CE earthquake over this period, but the actual timespan may be shorter and begin when gyttja deposits on slopes became thick enough to be prone to failure from such an event. [ABSTRACT FROM AUTHOR]

Co-delivery of different protein-encoding polynucleotide species with varying expression kinetics of their therapeutic product will become a prominent requirement in the realm of combined nucleic acid(NA)-based therapies in the upcoming years. The current study explores the capacity for time-staggered expression of encoded proteins by simultaneous delivery of plasmid DNA (pDNA) in the core and mRNA on the shell of the same nanocarrier. The core is based on a Gelatin Type A-pDNA coacervate, thermally stabilized to form an irreversible nanogel stable enough for the deposition of cationic coats namely, protamine sulfate or LNP-related lipid mixtures. Only the protamine-coated nanocarriers remained colloidally stable following mRNA loading and could successfully co-transfect murine dendritic cell line DC2.4 with fluorescent reporter mRNA(mCherry) and pDNA (pAmCyan1). Further investigation of the protamine-coated nanosystem only, the transfection efficiency (percentage of transfected cells) and level of protein expression (mean fluorescence intensity, MFI) of mRNA and pDNA, simultaneously delivered by the same nanocarrier, were compared and kinetically assessed over 48 h in DC2.4 using flow cytometry. The onset of transfection for both nucleotides was initially delayed, with levels < 5% at 6 h. Thereafter, mRNA transfection reached 90% after 24 h and continued to slightly increase until 48 h. In contrast, pDNA transfection was clearly slower, reaching approximately 40% after 24 h, but continuing to increase to reach 94% at 48 h. The time course of protein expression (represented by MFI) for both NAs essentially followed that of transfection. Model-independent as well as model-dependent kinetic parameters applied to the data further confirmed such time-staggered expression of the two NA's where mRNA's rate of transfection and protein expression initially exceeded those of pDNA in the first 24 h of the experiment whereas the opposite was true during the second 24 h of the experiment where pDNA displayed the higher response rates. We expect that innovative nanocarriers capable of time-staggered co-delivery of different nucleotides could open new perspectives for multi-dosing, pulsatile or sustained expression of nucleic acid-based therapeutics in protein replacement, vaccination, and CRISPR-mediated gene editing scenarios. [ABSTRACT FROM AUTHOR]

Earthquakes and tsunamis are natural phenomena that have strongly affected communities located along the Chilean active plate margin. Large-magnitude megathrust earthquakes produced at the plate interface of the subduction zone and their associated tsunamis have repeatedly impacted the Chilean coast, leaving a sedimentary record at particular sites from historic and prehistoric times. Here we assess paleoseismic sites related to late Holocene (< 1.5 ka) earthquakes and tsunamis that occurred along the Pacific coastline of south-central Chile (38°-42°S), which record critical information for the study of megathrust earthquakes. We focus on sites along the Valdivia segment that were affected by the great earthquake and tsunami of 1960 (Mw = 9.5; the largest recorded by modern seismology), which host geologic evidence of coseismic land-level changes found in tidal marshes and wetlands. We present an inventory of seven paleoseismic geosites composed mainly of different layers of buried soils and sand deposits, and a quantitative assessment of their scientific value, their potential touristic and educational value, and their degradation risk. These sites are considered part of the paleoseismic heritage of Chile and are relevant globally. Our inventory contributes to the establishment of management strategies for geoconservation of the coastal area of south-central Chile, and the mitigation of the effects of seismological hazards through the promotion of educational, touristic and outreach activities. [ABSTRACT FROM AUTHOR]