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Israel M. Kirzner, more than any other economist in the post-World War II era, has revived our understanding of the systemic role of the entrepreneur as the driving force of [...]

Abstract Regular exercise has both immediate and long-lasting benefits on cardiometabolic health, and has been recommended as a cornerstone of treatment in the management of diabetes and cardiovascular conditions. Exerkines, which are defined as humoral factors responsive to acute or chronic exercise, have emerged as important players conferring some of the multiple cardiometabolic benefits of exercise. Over the past decades, hundreds of exerkines released from skeletal muscle, heart, liver, adipose tissue, brain, and gut have been identified, and several exerkines (such as FGF21, IL-6, and adiponectin) have been exploited therapeutically as exercise mimetics for the treatment of various metabolic and cardiovascular diseases. Recent advances in metagenomics have led to the identification of gut microbiota, a so-called “hidden” metabolic organ, as an additional class of exerkines determining the efficacy of exercise in diabetes prevention, cardiac protection, and exercise performance. Furthermore, multiomics-based studies have shown the feasibility of using baseline exerkine signatures to predict individual responses to exercise with respect to metabolic and cardiorespiratory health. This review aims to explore the molecular pathways whereby exerkine networks mediate the cardiometabolic adaptations to exercise by fine-tuning inter-organ crosstalk, and discuss the roadmaps for translating exerkine-based discovery into the therapeutic application and personalized medicine in the management of the cardiometabolic disease.

Abstract Breast cancer is the most diagnosed cancer worldwide and represents the fifth cause of cancer mortality globally. It is a highly heterogeneous disease, that comprises various molecular subtypes, often diagnosed by immunohistochemistry. This technique is widely employed in basic, translational and pathological anatomy research, where it can support the oncological diagnosis, therapeutic decisions and biomarker discovery. Nevertheless, its evaluation is often qualitative, raising the need for accurate quantitation methodologies. We present the software BreastAnalyser, a valuable and reliable tool to automatically measure the area of 3,3’-diaminobenzidine tetrahydrocholoride (DAB)-brown-stained proteins detected by immunohistochemistry. BreastAnalyser also automatically counts cell nuclei and classifies them according to their DAB-brown-staining level. This is performed using sophisticated segmentation algorithms that consider intrinsic image variability and save image normalization time. BreastAnalyser has a clean, friendly and intuitive interface that allows to supervise the quantitations performed by the user, to annotate images and to unify the experts’ criteria. BreastAnalyser was validated in representative human breast cancer immunohistochemistry images detecting various antigens. According to the automatic processing, the DAB-brown area was almost perfectly recognized, being the average difference between true and computer DAB-brown percentage lower than 0.7 points for all sets. The detection of nuclei allowed proper cell density relativization of the brown signal for comparison purposes between the different patients. BreastAnalyser obtained a score of 85.5 using the system usability scale questionnaire, which means that the tool is perceived as excellent by the experts. In the biomedical context, the connexin43 (Cx43) protein was found to be significantly downregulated in human core needle invasive breast cancer samples when compared to normal breast, with a trend to decrease as the subtype malignancy increased. Higher Cx43 protein levels were significantly associated to lower cancer recurrence risk in Oncotype DX-tested luminal B HER2- breast cancer tissues. BreastAnalyser and the annotated images are publically available https://citius.usc.es/transferencia/software/breastanalyser for research purposes.

Abstract Background The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamina. Lamins have been associated with important cellular functions: DNA replication, chromatin organization, differentiation of the cell, apoptosis and in maintenance of nuclear structure. Little is known regarding the etiopathogenesis of adhesive capsulitis (AC); recently, a dysregulating fibrotic response starting from a subpopulation has been described within the fibroblast compartment, which suddenly turns on an activated phenotype. Considering the key role of A-type lamins in the regulation of cellular stability and function, our aim was to compare the lamin A/C expression between patients with AC and healthy controls. Materials and methods A case–control study was performed between January 2020 and December 2021. Tissue samples excised from the rotator interval were analysed for lamin A/C expression by immunohistochemistry. Patients with AC were arbitrarily distinguished according to the severity of shoulder flexion limitation: ≥ 90° and 0.05). Considering only patients with AC, lamin A/C intensity staining was found to be significantly higher in samples where acute inflammatory infiltrate was detected (p: 0.004). No significant changes in levels of lamin A/C expression were documented between the mild and severe adhesive capsulitis severity groups. Conclusions Our study demonstrated that the activity of lamin A/C in maintaining nuclear structural integrity and cell viability is decreased in patients with adhesive capsulitis. The phase of the pathogenetic process (freezing and early frozen) is the key factor for cell functionality. On the contrary, the clinical severity of adhesive capsulitis plays a marginal role in nuclear stability. Level of evidence III.

In a blend of poly(lactic acid) (PLA) and thermoplastic starch (TPS), a 15% load of hemp seed lignocellulosic filler (HF) was incorporated. Additionally, separate petrochemical-based compatibilizers, such as dicumyl peroxide (DCM) and benzoyl peroxide (LRL), as well as a bio-based compatibilizer, maleinized hemp seed oil (MHO), were introduced. Adding HF to the PLA/TPS blend reduced tensile mechanical properties due to the stress concentration phenomenon arising from the lack of interaction between components, yielding a more brittle material. This issue was mitigated by adding compatibilizers, notably the incorporation of MHO into the PLA/TPS/HF blend this increased elongation at break by enhancing compatibility among the blend components and providing a plasticizing effect. Moreover, regarding thermal properties, it was observed that the inclusion of HF led to a decrease in the glass transition temperature (Tg), cold crystallization temperature (Tcc), and melting temperature (Tm). Conversely, adding MHO to this blend increased all these values compared to the PLA/TPS/HF mixture, attributed to the plasticizing effect imparted by the modified oil. Additionally, following fracture in Charpy impact testing, the samples were subjected to field emission scanning electron microscopy (FESEM) analysis to examine the fractured surface of the various samples.

Human-Machine Interfaces (HMIs) play an important role in ensuring performance reliability to create safety and comfort during the operation of autonomous vehicles, by efficiently communicating their current state and driving intentions to drivers, passengers, and pedestrians. The motivation for this study emerges from the increasing development of autonomous vehicles and the critical need for effective HMIs to bridge the communication gap between these vehicles and their users. Examples of HMI technologies include visual displays for status updates, auditory alerts for immediate hazards, and haptic feedback for enhanced control. During automated driving tasks that may require users to take control of the vehicle under certain conditions, the interfaces must support the situational awareness of the drivers by providing effective communication of the situation. Design challenges include ensuring intuitive interaction, minimizing driver distraction, and achieving seamless integration with advanced vehicle control systems. The objective of this literature review is to present a comprehensive overview of the development of human-machine interface technologies in autonomous vehicles in different domain areas and to identify design challenges and opportunities to improve their interaction with their users.

This paper is a review of chosen reports on the integration of photovoltaics and agrotechnics and also presents the concept of an agro-photovoltaic foil tunnel module. This concept assumes the possibility of integrating modules into intelligent agro-photovoltaic fields. The proposed solution combines cultivation in a foil tunnel with a photovoltaic farm. The paper reviews electronic solutions to control ambient parameters, particularly those influencing the rate of photosynthesis in foil tunnels. The article also presents an analysis of the energy and water balances of the module in 4 different climate zones, including locations in Poland, Spain, Algeria, and Colombia. The module’s water requirements include drip irrigation and fogging systems. Water is assumed to be obtained from rainfall, desalination, non-conventional (treated, desalinated) resources, groundwater, and sub-artesian wells. The module’s energy needs include electricity consumption for pumping freshwater, desalination and water treatment, irrigation and fertilization, additional lighting and heating of plants, folding and unfolding of foil covers, and energy consumption related to automation. The article also analyzes crop shading by solar panels and its impact on the selected crop. The functionality of the presented solution was assessed for tomato cultivation in the four selected areas. A 240 m2 foil tunnel was considered. 60 m2 of the tunnel was covered by PV panels. The analysis results show that the most energetically effective agro-photovoltaic cultivation of tomatoes appears to be in the Saharan region of Africa where a 16 MWh annual energy surplus was obtained. Cultivations in Spain (Cartagena) and Colombia (Cali) seem to be slightly less effective, with approximately 15.5 MWh/a. The least effective agro-photovoltaic cultivation of tomatoes proved to be in Poland where the energy surplus reached 8.5 MWh/a. However, the economic return from cultivation strongly depends on local energy and tomato prices. The system of smart tunnels proposed by the authors combines photovoltaics with controlled protection of crops against unfavorable and extreme climatic conditions. In addition, the system allows plants to be grown with the maximum possible days with natural growing conditions, i.e. with uncovered tunnels, with natural bio-fertilization, and with natural sunlight.

Objetivo: revisar la literatura existente indagando por los tipos de lesión o enfermedad que se han identificado en supervivientes de artefactos explosivos improvisados (AEI), así como aspectos individuales y colectivos relacionados con la protección o destrucción de la salud humana enfrentada a los AEI. Metodología: revisión sistemática exploratoria de literatura publicada en bases de datos, como PubMed, SciELO, LILACS, JSTOR, OpenGrey y Google Scholar, entre 2001 a 2021 en cualquier localización geográfica. Se incluyeron artículos de investigación, de revisión o reflexión, libros o capítulos de libro de investigación e informes técnicos, en inglés, español, francés y portugués. Resultados: cumplieron con los criterios de inclusión y fueron revisados 76 documentos. Se han reportado múltiples lesiones asociadas al uso de los AEI, sin que exista un patrón característico de lesión o enfermedad; no obstante, la lesión más común es la amputación bilateral de miembros inferiores. En supervivientes se ha encontrado que el personal militar afectado suele mostrar una mayor capacidad de resiliencia, calidad de vida, tratamiento oportuno y capacidad física funcional más alta, comparado con civiles. El apoyo social genera efectos positivos en la salud y bienestar de los afectados. Conclusiones: los AEI generan múltiples afectaciones a la salud humana, físicas y psicosociales, los cuales requieren una atención integral y multidisciplinaria para el tratamiento, rehabilitación y reintegración de los supervivientes. Los aspectos protectores y destructivos identificados se encuentran asociados a mejores o peores resultados en la salud, existe una representación desigual entre civiles y militares.

Abstract Background The clam Chamelea gallina is an ecologically and economically important marine species in the Northwestern Adriatic Sea, which currently suffers from occasional, and still unexplained, widespread mortality events. In order to provide some glimpses in this direction, this study explores the connections between microbiome variations at the clam-sediment interface and the nutritional status of clams collected at four Italian production sites along the Emilia Romagna coast, with different mortality incidence, higher in the Northern sites and lower in the Southern sites. Results According to our findings, each production site showed a peculiar microbiome arrangement at the clam-sediment interface, with features that clearly differentiate the Northern and Southern sites, with the latter also being associated with a better nutritional status of the animal. Interestingly, the C. gallina digestive gland microbiome from the Southern sites was enriched in some health-promoting microbiome components, capable of supplying the host with essential nutrients and defensive molecules. Furthermore, in experiments conducted under controlled conditions in aquaria, we provided preliminary evidence of the prebiotic action of sediments from the Southern sites, allowing to boost the acquisition of previously identified health-promoting components of the digestive gland microbiome by clams from the Northern sites. Conclusions Taken together, our findings may help define innovative microbiome-based management strategies for the preservation of the productivity of C. gallina clams in the Adriatic Sea, through the identification and maintenance of a probiotic niche at the animal-sediment interface.

Abstract Phosphomannomutase deficiency (PMM2-CDG) leads to cerebellar atrophy with ataxia, dysmetria, and intellectual deficits. Despite advances in therapy, the cognitive and adaptive profile remains unknown. Our study explores the adaptive profile of 37 PMM2-CDG patients, examining its association with parental stress and medical characteristics. Assessment tools included ICARS for the cerebellar syndrome and NPCRS for global disease severity. Behavioral and adaptive evaluation consisted of the Vineland Adaptive Behavior Scale and the Health of the Nation Outcome Scales. Psychopathological screening involved the Child Behavior Checklist and the Symptom Check-List-90-R. Parental stress was evaluated using Parental Stress Index. Results were correlated with clinical features. No significant age or sex differences were found. ‘Daily living skills’ were notably affected. Patients severely affected exhibited lower adaptive skill values, as did those with lipodystrophy and inverted nipples. Greater severity in motor cerebellar syndrome, behavioral disturbances and the presence of comorbidities such as hyperactivity, autistic features and moderate-to-severe intellectual disability correlated with greater parental stress. Our study found no decline in adaptive abilities. We provide tools to assess adaptive deficits in PMM2-CDG patients, emphasizing the importance of addressing communication, daily living skills, and autonomy, and their impact on parental stress in clinical monitoring and future therapies.

The present work describes, for the first time, the chemical modification and characterization of epoxy resins derived from Brazil nut oil (BNO). The development of a bio-based resin has been carried out by chemically modifying BNO, resulting in epoxidized Brazil nut oil (EBNO). Moreover, through a maleinization process, a crosslinker based on maleinized Brazil nut oil (MBNO) has been employed. Analysis using techniques like iodine value (IV) and oxirane oxygen content (Oo) indicate successful chemical modification. FTIR analysis confirms the presence of reactive functional groups in both EBNO and MBNO, which are responsible for resin crosslinking. Mechanical testing of the different bio-resins developed shows that, in the cured resins, flexural strength and modulus decrease with increasing MBNO content, indicating improved flexibility due to the introduction of MBNO as a crosslinker. Thermal analysis using differential scanning calorimetry (DSC) reveals exothermic peaks corresponding to resin curing appearing at progressively lower temperatures. Therefore, this study successfully modifies BNO and demonstrates its effectiveness as a precursor to develop bio-based epoxy resins. The resulting resins exhibit improved ductile and thermal properties, making them suitable for various applications requiring low mechanical stresses.

The serious widespread development of nematode resistance has motivated the use of combined anthelmintic formulations. However, the advantages/disadvantages of the combined use of anthelmintics require further scientific characterization. The goals of the current trial were a) to characterize the pharmacokinetics of closantel (CLO) and moxidectin (MXD) administered both subcutaneously (sc) and orally either separately or co-administered (CLO + MXD) to lambs; b) to compare the nematodicidal activity of both molecules given individually or co-administered to lambs infected with resistant nematodes. Seventy (70) Corriedale lambs naturally infected with multiple resistant gastrointestinal nematodes were involved in the pharmacokinetic and efficacy trials. The animals were allocated into six groups (n = 10) and treated with either CLO, MXD, or with the CLO + MXD combined formulation by both the oral and sc routes. Additionally, an untreated control group (n = 10) was included for the efficacy trial. The efficacy was estimated by the faecal egg count reduction test (FECRT). Higher systemic exposure of both CLO and MXD was observed after the sc compared to the oral administration in lambs. The combined administration of CLO + MXD did not markedly alter their disposition kinetics. At 13 days post-treatment, the administration of both molecules as a single active principle reached efficacy levels ranging between 80% (MXDoral), 84% (CLOoral), 85% (CLOsc), and 92% (MXDsc). The combined oral and sc treatments reached 99% efficacy. No adverse effects were observed after the combined treatment of CLO + MXD, and their co-administration did not show any adverse pharmacokinetic interaction. The combined effect of CLO + MXD successfully restored the maximum efficacy levels, which were not reached by the individual active ingredients.

Fake news can generate memory distortions and influence people's behavior. Within the framework of the great debates, the tendency to generate false memories from fake news seems to be modulated by the ideological alignment of each individual. This effect has been observed mainly around issues involving large sectors of society, but little is known about its impact on smaller-scale discussions focused on more specific populations. In this work we examine the formation of false memories from fake news in the debate between psychological currents in Argentina. For this, 326 individuals aligned to psychoanalysis (PSA) or Evidence-Based Practices (EBP) observed a series of news (12 true and 8 fabricated). The EBP group remembered or believed more fake news that damaged PSA. They also remembered with greater precision the statements of the news that harmed their own school, than those referring to others. These results could be understood as the product of an imbalance in the commitment between the different parties, since the group that proposes the paradigm shift (EBP) exhibited a congruence effect, while the group whose orientation is hegemonic in this field (PSA) did not show any effect of ideological alignment. The fact that the congruence effect is manifested to some extent in settings as relevant as the education of mental health professionals, highlights the need to move towards more careful practices in the consumption and production of media.

Dengue is an emerging disease of high impact on human health. Plants are an important source of new antivirals and Arachis hypogaea stands for its biological properties. The aim of this study was to evaluate the cytotoxicity and antiviral activity and elucidate the antiviral mechanism of ethanolic extracts from A. hypogaea against dengue virus 2 (DENV-2). The skin or tegument ethanolic extract (TEEs) and seed ethanolic extract (SEEs) were obtained. Cytotoxicity was evaluated by MTT and Neutral Red Uptake (NRU). Antiviral activity was evaluated at different stages of the viral replication cycle by the lysis plaque reduction method. The 50% inhibitory concentration (IC50) and selectivity index (SI) were determined. Antiviral activity was further determined by RT-qPCR. The CC50 values were 169 (NRU) and 65 (MTT) µg/mL for TEE. In addition, the CC50 values were >1400 (NRU) and 636 (MTT) µg/mL for SEE. The TEE demonstrated 99.9 ± 0.1% viral inhibition. The TEE presented an IC50 = 3.47 and SI of 48.7 (NRU) and 18.73 (MTT). Its mechanism of antiviral action is broad and it acts in the viral adsorption–penetration stage and inhibits the first steps of infection in the post-penetration stage. It is also capable of acting as virucidal and as prophylactic. Studies of RT-qPCR indicated that the TEE inhibited viral RNA synthesis. These findings suggest that the TEE from A. hypogaea could be a promising antiviral candidate for treating DENV-2 infections.

Symbiosis establishment between Trichoderma atroviride and plant roots triggers the priming of defense responses, among other effects. Currently, there is no clear evidence regarding the molecular mechanisms that allow the plant to remain alert to future stimulus, either by pathogen attack or any other abiotic stress. Epigenetic modifications have emerged as a strategy to explain the increased defense response of plants in a priming state conferred by Trichoderma. Recently, various non-canonical structures of nucleic acids, especially G-quadruplex structures (G-quadruplexes or G4s), have been identified as potential targets during the establishment or maintenance of plant signals. In the present study, we developed a screening test for the identification of putative G4-forming sequences (PQSs) in previously identified Z. mays priming genes. Bioinformatic analysis revealed the presence of PQSs in the promoter region of five essential genes playing a critical role in priming in maize. Biophysical and spectroscopy studies showed the formation of G4s by these PQSs in vitro, and ChIP assays demonstrate their formation in vivo. Therefore, G4 formation could play a role as an epigenetic regulatory mechanism involved in the long-lasting primed state in maize plants.

Objectives: One of the behavioral problems strongly associated with emotional dysregulation (ED) in ASD is emotional outbursts (EOs) characterized by a pattern of challenging behavior that varies across individuals and across time. Cultural factors can modulate the expression of EOs. This study aimed to characterize the profile of emotional outbursts (EOs) in children with autism spectrum disorder (ASD) across various countries in Latin America and to identify clinical, emotional, and contextual factors that contribute to the onset and frequency of EOs within this diverse sample. Methods: A cross-sectional and cross-cultural study was conducted between 2023 and 2024 comprising samples from five countries in the Latin American Network for Autism-REAL: Argentina, Brazil, Chile, Uruguay, and the Dominican Republic. We studied 689 children with ASD (age x = 8.7 ± 2.6 years) using the Emotional Outburst Questionnaire (EOQ). Results: We identified different types of EO among children with ASD in our sample. The most frequent was the ‘behavioral indicators of emotion’ (52.0%) followed by ‘increased motor activity’ (28.3%), ‘non-speech vocalizations’, (27.6%), ‘mild verbal aggression’ (23.8%), and ‘avoidance’ (21.5%). Children in a bad mood or having a bad day or experiencing irritability were the most significant factors that increased the likelihood of EOs. Conclusions: Our results revealed that irritability is an important trigger for EOs and should not be disregarded or underestimated when monitoring the mental health of children with ASD.

A fracture-related infection (FRI) is a severe complication of an orthopedic trauma, often leading to challenging treatments and poor outcomes. The surgical strategies are typically categorized into one-stage or two-stage procedures, with the use of systemic and local antibiotics being crucial for infection management. This study assessed the efficacy of an antibiotic-loaded hydrogel (ALH) applied over the internal fixation devices for treating FRIs, comparing the outcomes between the one-stage (OS) and two-stage (TS) reconstructions. This retrospective study included 17 patients with an FRI treated using the ALH at a single center. The patients were divided into OS and TS reconstruction groups. The data on demographics, surgical procedures, antibiotic regimens, and outcomes were collected. The primary and secondary outcomes included the infection cure rate, bone union, complications, and reoperation rates. Among the 17 patients (mean age 48.5 years, 16 males), infections were predominantly in the tibia, with 12 chronic and 5 acute cases. Seven patients had monomicrobial infections, and nine had multidrug-resistant pathogens. No significant differences were found between the OS and TS groups in terms of the infection cure rate, bone union, or complications. One patient in the OS group experienced an infection recurrence, and bone healing was achieved in all but one case. Additional complications included delayed wound closure in two cases and implant failure in one case, requiring a reoperation. The ALH demonstrated potential as an effective local antibiotic treatment for FRIs, particularly in the one-stage reconstructions, allowing for a safe application of internal fixation devices. However, further research with larger sample sizes and longer follow-ups is needed to validate these findings.

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed.

Goal 4 of the UN Sustainable Development Goals (SDGs) concerns inclusive, equitable quality education and promotion of lifelong learning opportunities for all. Libraries excel at early-education offerings and lifelong or recreational learning. However, less prevalent is support for the "middle"—adults with higher education aspirations. An educated workforce supports an information-resilient society, yet individuals in rural communities experience informational barriers and underrepresent degree holders. This research examines the provision of college planning programs and information in central Appalachia through a content analysis of 89 public library websites. Though the region enjoys a close-knit connectedness that could place libraries at the forefront of degree attainment and information resilience, findings suggest there is much room for improvement if the libraries aim to support goal 4 as related to postsecondary education. This research is relevant to audiences worldwide as postsecondary education has been shown to impact economic development in international lower-income contexts. [ABSTRACT FROM AUTHOR]

The objective of this research was to examine the relationship of the variables training and learning, and the diversity of sources of innovation's ideas, with the social innovation of non-profit organisations (NPOs). The study was carried out in Guayas-Ecuador. It is a quantitative, cross-sectional, and non-experimental study, in which Probit regression was used. The findings indicate that the variables: training and learning, and the diversity of sources of ideas for innovation, positively affect social innovation in these organisations. The theoretical implication of the research is that it contributes to the scant empirical evidence of this relationship, especially in developing countries; it also strengthens the idea that the resource-based view of the firm can explain social innovation and that the fundamental resource in social innovation is the knowledge that these organisations acquire and increase through training and internal learning, as well as the diversity of sources of ideas for innovation that they acquire.