Pancreatic neuroendocrine tumor (P-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional P-NETs, typically when liver metastases occur. NETs diagnosis is frequently late, along with symptoms related to hormone hypersecretion. We described the case of a patient with a low-grade non-functional P-NET, but with a typical clinical presentation of a carcinoid syndrome; moreover, we reviewed the literature regarding this topic. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hypervascular mass; then a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum Chromogranin A and urinary 5-HIAA measurements resulted negative. Given the small size of the lesion (8 mm), we preferred to perform an endoscopic ultrasonography (EUS) with fine-needle biopsy (EUS-FNB), allowing the diagnosis of low-grade (G1) non-functional P-NET (NF-P-NET). Surgery was waived, while a follow-up strategy was chosen. Early recognition of P-NETs, although rare, is necessary to improve patient’s survival. EUS-FNB should be the protocol of choice for an early characterization of these tumors.

Covid-19 fatality rates of 0.37% (Gangelt, Germany) and 0.17% (Santa Clara, USA) have been reported, estimated from serological studies. We show that the two confidence intervals strongly overlap when the uncertainty in the number of deaths is taken into account, so that the two investigations may be regarded as representative of the same population (tentatively: “Western society with no overload of the Health Care System during the pandemic”). Combining the results, the Covid-19 fatality rate is estimated to be found with 95% confidence in the range [0.1%; 0.3%].

Most police Mental Health Act (Section 136) detentions in England and Wales relate to suicide prevention. Despite attempts to reduce detention rates, numbers have risen almost continually. Although Section 136 has been subject to much academic and public policy scrutiny, the topic of individuals being detained on multiple occasions remains under-researched and thus poorly understood. A mixed methods study combined six in-depth interviews with people who had experienced numerous suicidal crises and police intervention, with detailed police and mental health records. A national police survey provided wider context. Consultants with lived experience of complex mental health problems jointly analysed interviews. Repeated detention is a nationally recognised issue. In South East England it almost exclusively relates to suicide or self-harm and accounts for a third of all detentions. Females are detained with the highest frequencies. The qualitative accounts revealed complex histories of unresolved trauma that had catastrophically damaged interviewee’s relational foundations, rendering them disenfranchised from services and consigned to relying on police intervention in repeated suicidal crises. A model is proposed that offers a way to conceptualise the phenomenon of repeated detention, highlighting that long-term solutions to sustain change are imperative, as reactive-only responses can perpetuate crisis cycles.

About 70% of children and adolescents with cerebral palsy experience gait impairments which affect their autonomy and well-being. Robotic-assisted gait training using the Lokomat is particu-larly promising for rehabilitation as it provides a standardized environment favoring the massive repetition of the movement, in which physical demands are low on the therapist and high training loads can be achieved. As no guidelines exist regarding training protocols and Lokomat settings, the goal of this study was to review the literature on Lokomat-assisted gait therapy and possibly make training recommendations. The twelve studies reviewed reported both positive and null effects of Lokomat training on gait. Half of the studies combined Lokomat with other types of training and only five used a control intervention to assess its benefit. Overall, training was administered 1-5 times per week for 20-60 minutes, over 1-12 weeks. Although Lokomat settings were not always described, progressively decreasing body-weight support and guidance, while increasing treadmill speed appear to be prioritized. The variety of training protocols and settings used did not allow pooling of the studies to assess effects of interventions on gait parameters in children and adoles-cents with cerebral palsy. This review highlights the need for homogenization of interventions so that clear guidelines can emerge and be applied in rehabilitation centers.

In the context of seismic risk, studying the characteristics of urban soils and of the built environment means adopting a holistic vision of the city taking a step forward compared to the current microzonation approach. Based on this principle, CLARA WebGIS aims to collect, organise, and disseminate the available information on soils and buildings in the urban area of Matera. The geodatabase is populated with i) 488 downloadable geological, geotechnical, geophysical, surveys; ii) geological, geomorphological, and seismic homogeneous microzones maps and iii) a new Digital Surface Model. The CLARA WebGIS (https://smartcities-matera-clara.imaa.cnr.it/) is the first publicly available database reporting for the whole urban area the spatial distribution of the fundamental frequencies for soils and the overlying 4043 buildings, along with probability levels of soil-building resonance. The WebGIS is addressed to a broad target of end users (local government, engineers, and geologists, etc.) as a support to the implementation of seismic risk mitigation strategies in terms of urban planning, seismic retrofitting, and management of post-earthquake crises. We recommend that the database be managed by local administrators, who would also have the task of deciding on future developments and continuous updating as new data becomes available.

We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

1) Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. 2) Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. 3) Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. 4) Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

Manual material handling (MMH) significantly impacts worker health and productivity, often leading to musculoskeletal disorders (MSDs) primarily in the lower back. As a novel assistive technology, exoskeletons may serve as ergonomic tools to mitigate these work-related MSDs. It is essential to examine exoskeletons from the users’ perspectives before their widespread implementation in occupational settings. This study investigates the effectiveness of a passive back-support exoskeleton (BExo) in reducing perceived physical exertion and improving ergonomic safety in manufacturing context. Twenty-two college students were recruited to perform MMH tasks in a controlled lab environment, both with and without the BExo, followed by completing a survey questionnaire on various aspects of the BExo. Using ANOVA, the study analyzed biomechanical exertion across various body parts and tasks. The findings indicate that the BExo substantially alleviates discomfort in the low back, shoulders and knees, thereby, enhancing ergonomic posture and reducing fatigue. These results underscore the potential of passive exoskeletons to boost workers’ safety and efficiency, providing valuable insights for future ergonomic strategies in industrial setting.

The EU has set the ambitious target of raising the share of EU energy consumption produced from renewable resources to 32% by 2030 with a target of climate neutrality by 2050. The aim of this paper is to assess the role of biomass usage in the context of these targets. The paper identifies progress made between 2013–2022 by focusing on a selection of EU countries. The largest bio-energy increments of 130PJ, 77PJ and 60PJ were reported for Poland, Sweden, and the Nether-lands. This study valuates the crucial role in co-generation and heat in EU regions, with biomass usage between 55-80% of the combined heat and power (CHP) energy in Nordic countries. The future perspectives for bioenergy based on EU policies, biomass resources and technical issues were addressed. The EU possess around 9% of the global biomass supply, ensuring a certain level of biomass resource dependence. Thus, the biomass usage demand in energy production, non-energy sectors and transport is expected to rise leading to increments of 13%-76% on biomass imports. It appears that bioenergy development is mostly limited by economic issues and uneven support for bioenergy in different EU countries as well as environmental issues. The study shows a promising and sustainable potential of bioenergy in the EU as a renewable energy source while minimizing negative impacts on the environment and the economy. By 2050, liquid biofuels are likely to be increasingly used in the transport sector. Non-energy sector usage of biomass is still in an early stage of development, except for the pulp and paper industry, and significant use of biomass in non-energy sectors seems unlikely in the near future.

Exopolysaccharides-EPS are long-chain biopolymer with branched, recurring unit of sugars and non-carbohydrate constituents connected to exterior of cells. Rhizobial, a legume nodulating organism is capable of producing EPS. This study investigated the characteristics’ of some Rhizobium EPS and their effects in shelf life extension of some Musa spp. Rhizobial-EPS was produced using yeast extract mineral medium purified by standard methods. The EPS was characterized to determine functional group, thermal stability, chemical compounds and the monosaccharide component using Fourier Transform Infra-red, Spectroscopy, thermogravimetric Analysis (TGA), Gas Chromatography–Mass Spectrometry and HPLC and their bio-preservative property on post-harvest quality of plantain and different banana was done. The Rhizobial-EPS functional groups were hydroxyl, carboxyl, amine, methyl and ethers associated with polysaccharides. Pentadecanoic acid, octadecanoic acid, oleic acid and heptacosanoic acid, and varied concentration of monosaccharides were detected in the exopolysaccharides. The TGA of the EPS shows a constant loss in weight with two quasi-sharp alterations and almost steady plateau. The EPS coated samples had the lowest weight loss across the samples and as such edible coating was effective in delaying weight loss. The weight loss of Musa paradisiaca (plantain) coated with (EPSA obtained from USDA 110), (EPSB USDA 532C) and (EPSC S2) at the first day were 314 and 314.5g. The initial weight loss of coated and uncoated Musa sp. (Apple Banana), Musa acuminata (Lady Finger), and Musa balbisiana (Cooking Banana), ranged from 72 – 72.7g, 96 – 97g and 95 – 98g respectively. The total sugar of EPS Coated Musa sp. ranges from 0.381 – 0.528mg/L, 0.392 – 0.576 mg/L and 0.41 – 0.598 mg/L at days 1, 2 and 3 respectively. The highest Titratable acidity and pH was observed in EPS coated sample. The results obtained from this study proves that EPS solution is a valuable product for fruit preservation and viable for commercial applications.

Zika virus (ZIKV), without a vaccine or no effective treatment approved as yet, have globally spread since the past century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in the last years, causing epidemics with greater infectivity, tropism towards new tissues, and other related symptoms as a product of various emergent ZIKV-host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons are less known. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 412 complete genomes in a phylogenomic scanning were used for studying the conservation of structured RNAs. We found specific genomic regions, which highlight their patterns of conserved RNA structures at the level of inter-geographical comparisons. We have proposed these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that occurred in specific geographic regions.

The study proposes planning independent children's mobility through geoinformation technologies for listening to children. This research assumes that children’s values and expectations must be considered in city planning. A bibliographic review identifies 15 indicators which make spaces safe and attractive for children to circulate and play. Thematic maps of the indicators are prepared, integrated by Multicriteria Analysis by Weights of Evidence, according to the hierarchical importance of each variable. The definition of weights considers the opinion of children and technicians. Consultation with children is carried out by Mapping Volunteers (VGI), Consultation on Hierarchy, Geodesign of Ideas for the area and Artistic Workshop. In the technical study, the query applies the Delphi method. It uses the VGI – Volunteered Geographic Information – web-based platform, where children record places of topophilia and topophobia, while technicians map the presence of 15 indicators. The set of information is made available on a web-based platform of SDI – Spatial Data Infrastructure, in which there are resources for a Geodesign workshop when ideas for the area are elaborated through negotiation and co-creation. The product is a transformation design for the area through urban design and parameterisation of uses.

We seek to examine effective collaboration when engaging in value cocreation with the customer for mobile financial services in EMs. Our study is a motivation for multi-stakeholder engagement in value cocreation with financial inclusion of all consumers including marginalized populations. Furthermore, our work discovers that social sustainability is a product of social creativity and results in financial inclusion. We apply a qualitative descriptive methodology utilizing exemplars from extant research and phenomenology to analyze the data from the contexts of Ghana and Kenya. The results show that value is co-created for mobile financial services in networks in emerging markets when actors integrate resources for social and environmental sustainability as essential elements for mobile financial inclusion.

In recent years, the role of non-coding RNAs (ncRNAs) in regulating cell physiology has begun to be better understood. Recent discoveries in viral molecular biology have revealed that such cellular functions are disturbed during viral infections mainly due to host cell ncRNAs, cellular factors, and virus-derived ncRNAs. Apart from the interplay between those molecules, other interactions derive from the specific folding of RNA virus genomes. These fulfill canonical regulation functions such as replication, translation, and viral packaging. In some cases, folds serve as precursors of small viral RNAs whose biogenesis is not yet clearly understood. Since ncRNAs and RNA viral genomes modulate complex molecular and cellular processes in viral infections, a new taxonomy is being proposed here overarching three main categories, considering the current information about ncRNA interactions in some well-known viral infections. The first category shows examples of host ncRNAs associated with the trigger of the immune response under viral infections. The second category describes interactions between the virus and host ncRNAs. The last category shows how the shape of the RNA viral genome is essential in processing RNAs derived from viruses. Finally, we introduce evidence of how these three categories can also work as a framework in order to organize known interactions of ncRNAs and cellular factors under DENV infection. This new taxonomy of interactions provides a comprehensive framework for organizing the ncRNA regulatory roles in the context of viral interactions and an RNA world.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

Geoethics is a field of knowledge currently in full development. Researchers in geoethics are pri-marily concerned with the anthropogenic interaction with the Earth system. Due to its nature, ge-oethics holds particular importance in sustainable development due to its nature as it aims to promote ethical human behaviour that does not negatively impact the Earth system. In the present research, we implemented an intervention program addressing various issues related to the sus-tainability of the Earth system, such as the exploitation of geological resources, the management of geological risks, and the conservation and promotion of geopatrimony. The intervention program was applied to higher education students in the geosciences field. A sample of 90 students from various geosciences courses completed an initial questionnaire, revealing limited knowledge about geoethics. This study resorted to mixed-method research involving interviews with some students who volunteered (n=52). The results showed that after applying the intervention programme most students had developed a deeper understanding of the topics addressed and recognised the con-tributions this scientific area can make to sustainable development. Additional research in geoethics education is essential to foster the integration of geoethics into the curricula of higher education institutions.

"Hidden hunger", the deficiency of important mineral micronutrients, affects more than 2 billion people globally. Adolescence is unquestionably a period of nutritional risk, given the high nutritional requirements for growth and development, erratic or capricious diets and the increased consumption of snacks. This study applied the rational food design approach to obtain micronutrient-dense biscuits by combining chickpea and rice flours to achieve an optimal nutritional profile, crunchy texture and appealing flavour. The perception of 33 adolescents of the suitability of such biscuits as a mid-morning snack was examined. Four biscuits were formulated, with different ratios of chickpea and rice flours (CF:RF): G100:0, G75:25, G50:50 and G25:75. Nutritional content, baking loss, acoustic-texture and sensory analyses were carried out. On average, the mineral content of biscuits with the CF:RF ratio of 100:0 doubled compared with the 25:75 formula. The dietary reference values for iron, potassium and zinc reached 100% in the biscuits with CF:RF ratios of 50:50, 75:25 and 100:0, respectively. The analysis of mechanical properties revealed that samples G100:0 and G75:25 were harder than the others. Sample G100:0 showed the highest sound pressure level (Smax). Sensory analysis showed that increasing the proportion of CF in the formulation augments the grittiness, hardness, chewiness and crunchiness. Most of the adolescents (72.7%) were habitual snack consumers; 52% awarded scores ≥ 6 to biscuit G50:50 for its overall quality, 24% described its flavour as "biscuit" and 12% as "nutty". However, 55% of the participants could not pinpoint any dominant flavour. In conclusion, it is possible to design nutrient-dense snacks that meet the micronutrient requirements and sensory expectations of adolescents by combining flours naturally rich in micronutrients.

The aim of this study was to evaluate the psychometric evidence of the original and brief version of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in Spanish in a sample of 245 Peruvian adolescents and adults (mean age = 21.04 years, SD = 3.07, 47.8% male and 52.2% female), selected by non-probabilistic convenience sampling. Additionally, the Coronavirus Anxiety Scale and the Satisfaction with Life Scale were applied. Confirmatory Factor Analysis, internal consistency reliability methods, hierarchical sequence of variance models and Graded Response Model were used. Results indicate that both versions of the SCSRFQ showed robust psychometric properties: adequate unidimensional structure, adequate difficulty and discrimination parameters, and significant relationships with the measures of fear of COVID-19 and satisfaction with life. The original version of the SCSRFQ showed evidence of strict measurement invariance by gender and age; whereas the short version showed strict invariance by gender and configural invariance by age. Both versions showed acceptable reliability indices. In conclusion, the original and brief versions of the SCSRFQ show evidence of psychometric indicators that support their use to assess the strength of religious faith

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

The chemistry and electrochemistry basic fields have been active since the last two decades of the past century studying how surface modification of electrodes by coating with conductive films enhances their activity and performance. In the light of the development of alternative sustainable ways of energy storage and carbon dioxide conversion by electrochemical processes, these research studies have jumped in the 21st century to more applied fields such as chemical engineering, energy and environmental science and engineering. The huge amount of literature on experimental works dealing with the development of CO2 electroreduction processes addresses electrocatalyst development. Membranes can help understanding and controlling the mass transport limitations of current electrodes and reactors designs. The present bibliometric review addresses the papers published in the 21st century regarding membrane coated electrodes and electrocatalysts to enhance electrochemical reactor performance and viability with a special focus on the urgent issue of carbon dioxide capture and utilization.

In most econometrics literature, the Autoregressive Distributed Lag (ARDL) model is often applied in many economic analyses to study short and long run relationships. This is because ARDL model can deal with economic variables that are integrated of different order (I(0), I(1) or combination of both) and also it is robust where there is single long-run relationship between the underlying variables in a simple sample size. This study applied the ARDL model to examine the contributions of commercial Banks to GDP growth in Nigeria. To achieve this, annual data covering 1981 to 2015 for loans and advances, savings, lending rates and GDP of Financial Institutions were collected from CBN bulletin. The ADF test revealed that the variables are I(1) except for lending rate which was of I(0) order. The ARDL(1,1,1,2) model revealed that loans and advances, and lending rates are significantly positively related to GDP in Nigeria but savings was not significant in the model. The model revealed some evidence of short run relationships while the ecm(-1) was -0.6156 (P-value=0.0038<0.05) which means that the rate of the speed of adjustment to equilibrium is 61.56% annually. The estimated model is free from serial correlation, multicollinearity, heteroscedasticity while the model is stable and the residuals are normally distributed. The study recommends that savings and savings culture should be encouraged in Nigeria since economic theory states that savings and investment are related in any economic development.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

As a result of the growing demand for foods with reduced animal protein content, many new alternative diets are now emerging. Nevertheless, recent studies have shown that the Western population is unprepared for drastic changes and is disinclined to accept foods based on alternative proteins. However, hybrid products might become a good transitional offer. This study used a desirability-based mixture design to model hybrid spreadable cheese analogues (SCAs). The design combined the dairy protein (MPC), Tenebrio molitor (IF) and faba bean (FBP) flours. Nine SCAs with different MPC/FBP/IF ratios were formulated, representing 0, 50 and 100% MPC replacement (7.1% of the formula). Incorporating the IF negatively impacted the desirable texture properties. The FBP flour improved the texture (achieving increased firmness and stickiness and decreased spreadability), but only when combined with MPC. Changing the MPC/FBP/IF ratio affected the colour of SCAs. Sensory analysis showed that hybrid SCAs (≤ 50% MPC) had a more characteristic cheesy flavour than the commercial plant-based reference, and sample C2 had a texture profile similar to the dairy reference. Samples containing IF showed a better flavour profile than the products without IF. The SCAs had higher protein and lower saturated fat, starch and sugar con-tent than commercial analogues.This study demonstrates that the inclusion of alternative proteins can be effective as a strategy to reduce dairy protein content in hybrid product formulations.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

The diagnosis and the pathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. In this work, we took advantage of a large public dataset on the IgG antibodies to 3,054 EBV peptides to understand whether these immune responses could be used as putative biomarkers for disease diagnosis and triggers of pathological autoimmunity in ME/CFS patients using healthy controls (HCs) as a comparator cohort. We then aimed at predicting disease status of study participants using a Super Learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. When we compared data of all ME/CFS patients or data of a subgroup of these patients with non-infectious or unknown disease trigger to the dataset of HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. In contrast, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from HCs with 100% and 90% accuracies on the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis of a subset of patients, but they are less likely to trigger pathological autoimmune responses that could explain the pathogenesis of ME/CFS.

(1) Background: In Eugenia Stipitata Mac Vaugh (Arazá), there is an abundance of flavonoids, carotenoids, and phenolic acids, which are bioactive compounds with antioxidant, anticarcinogenic, antimicrobial, anti-inflammatory, antispasmodic, antiulcer, and cardiovascular disease prevention benefits. Therefore, the aim of this review is to compile the compounds that have been identified in the fruit and gather information about secondary metabolites to establish their potential preventive and therapeutic effects; (2) Methods: a literature search was conducted in repositories and databases such as Science Direct, Scopus, PubMed, Web of Science, Agriculture Collection Gale, SAGE, OXFORD University, DOAJ, among others. Articles identifying and quantifying bioactive compounds present in Arazá were included; (3) Results: Five studies meeting the inclusion criteria were incorporated, resulting in the compilation of 82 compounds, of which 24 were identified and quantified, while 58 were solely identified. This review was able to identify and report the concentration, and in some cases, the quantity, of phenolic compounds with antioxidant and anti-inflammatory capabilities present in Arazá; (4) Conclusions: With this scope, it was possible to obtain a more comprehensive understanding of the fruit's potential to potentially enhance health aspects, thereby providing greater prominence and added value to this product, allowing for more frequent inclusion in the diets of consumers, and even enabling exportation.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Our results showed bacterial growth rates of 2.31 and 2.44 d–1 without and with seagrass, respectively. In seagrass chambers, bacterial growth was higher than that in non-seagrass chambers, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, we observed a negative Synechococcus spp. growth rate (-0.9 d–1) in the seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

Cognitive impairment in older adults is associated with poor gait performance, physical decline, falls and poor quality of life. This paper analyzes the feasibility and efficacy of a tango-based in-tervention in older people with cognitive impairment living in nursing homes. A multicenter study, with pre and post-test, was carried out. Intervention attendance, well-being, physical abilities (Short Physical Performance Battery), walking performance, functional capacities (Katz Index), and quality of life (Quality of Life in Alzheimer’s Disease) were assessed. Fifty-four participants (84.9 ± 6.7 years, Mini Mental State Examination 14.5 ± 7.4) completed the protocol. Intervention attendance was 92%, and the mean subjective well-being after each session was 4.5 ± 0.5 (on a five-point scale). Statistically significant improvement was found in the quality of life (p = 0.030). Non statistically significant changes were found in walking performance, physical abilities, or in functional capacities. The study shows feasibility and suggests evidence for the effects of Tango therapy on well-being and quality of life. Further studies are necessary to contrast these findings and to verify the role of Tango interventions as a holistic approach to prevent functional decline in older people with cognitive impairment.

The clinical application of Phentolamine Mesylate (PM) as an anaesthetic reversal agent has been documented in paediatric patients and in conservative dentistry, but no studies have been found in implant surgery. A prospective randomised study was conducted in 60 patients eligible for mandibular implant treatment, randomly divided between the Control Group (CG) and Experimental Group (EG), who were administered PM. Haemodynamic changes, adverse effects and patient satisfaction were assessed. No statistically significant differences in haemodynamic changes and postoperative pain were found between CG and EG (p&lt;0.05), except for Systolic Blood Pressure (SBP) which increased slightly in EG, without posing a risk to the patient. There were no differences in the presence of adverse effects between the two groups, except in the CG which presented greater difficulty in chewing and biting (p&lt;0.05) and the EG with greater pain in the injection area (p=0.043). 83.3% of the EG patients would request PM again for future dental treatment. The use of PM offers an alternative in implant surgery, without increasing the risks and increasing the patient's quality of life.

Several studies have already demonstrated the relationship between the loss of natural habitats and the incidence of diseases caused by vectors, such as dengue, which is an acute fever disease, considered a serious public health problem. The aim of the present study was to analyze the relationship between land use changes between 2009 and 2019 and the occurrence of dengue fever in 2015 and 2019 by municipality, using the state of Minas Gerais as a case study. For this, secondary data obtained from openly available sources were used. Natural vegetation cover data were obtained from the MAPBiomas platform and dengue occurrence data from the Ministry of Health, in addition to socioeconomic indicators from the Brazilian Institute for Geography and Statistics. Between 2015 and 2019, 1,255,731 cases of dengue were recorded throughout the state of Minas Gerais, ranging from 0 to 227 per thousand inhabitants between municipalities. The occurrence of dengue was distributed throughout all regions of Minas Gerais, affected by climatic and socioeconomic aspects. In general, municipalities with net loss of natural vegetation, predominantly located in the Cerrado biome, had the highest number of dengue cases in the studied period. Despite the significant positive relationship between these two variables, three of the eight socioeconomic parameters analyzed also affected the occurrence of dengue: population density, human development index (both positively) and Gini inequality index (negatively). These results indicate that, contrary to expectations, municipalities with better social conditions had more dengue cases. Our study indicates that natural vegetation is, directly or indirectly, involved in the ecosystem service of dengue control, despite the occurrence of this disease being affected by multiple factors that interact in a complex way. Thus, policies towards reducing deforestation must be complemented by a continuous investment in public health policies and reduction of social inequalities to efficiently control dengue fever.

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

Background: The aim of this study was to design and analyze the content validity of an instrument to assess the risk of behaviors associated with the Chemsex phenomenon since there is currently no instrument with this objective. Method: Firstly, a bank of items identified from the literature was elaborated. Secondly, 50 experts with knowledge of the Chemsex phenomenon at the national level were contacted. A Delphi group was formed with them to carry out two rounds of item evaluation (comprehension and appropriateness) using a Likert scale of 1 to 5. To assess linguistic validity, the mean score of the item comprehension scores was used. The content validity index (CVI) and Aiken's V (VdA) were calculated for each item. A minimum value of CVI and VdA of 0.6 was established to include the items in the questionnaire. Results: In the first round of evaluation, 36 experts evaluated 114 items, of which 61 were selected. In a second round, 30 experts evaluated the 61 items selected, leaving the scale finally made up of 52 items. Conclusion: A questionnaire has been designed to assess the risk of behaviors associated with the Chemsex phenomenon. The items that make up the questionnaire have shown adequate content and linguistic validity, so this instrument can be considered valid. The Delphi method proved to be a useful technique for the proposed objective.

Background. The treatment of coronary stenosis relies on invasive high risk surgical assessment to generate the fractional flow reserve diagnostics index, a ratio of distal to proximal pressures in respect of coronary atherosclerotic plaque causing stenosis. Non-invasive methods are therefore a need of the times. This study proposes an extensible mathematical description of the coronary vasculature that permits rapid estimation of the coronary fractional flow reserve. Methods. By adapting an existing closed loop model of human coronary blood flow, the effects of large vessel stenosis and microvascular disease on fractional flow reserve were quantified. Several simula-tions generated flow and pressure information which was used to compute fractional flow re-serve under a spectrum of conditions including focal stenosis, diffuse stenosis, and microvascular disease. Sensitivity analysis stratified the influence of model parameters on the index. The model was simulated as coupled non-linear ordinary differential equations and numerically solved us-ing an implicit higher order method. Results. Large vessel stenosis affected fractional flow re-serve. The model predicts that the presence, rather than severity, of microvascular disease affect coronary flow deleteriously. Sensitivity analysis revealed that heart rate may not affect the index. Conclusions. The model provides a computationally inexpensive instrument for future in silico coronary blood flow investigations as well as clinical-imaging decision making. A combination of focal and diffuse stenosis appears to be essential in reducing the index. In addition to pressure measurements in the large epicardial vessels, diagnosis of microvascular disease is essential. The independence of the index with respect to heart rate suggests that computationally inexpensive steady state simulations may provide sufficient information to reliably compute the index.

Micromobility has gained attention from policymakers, industry stakeholders, and academia; however, a comprehensive conceptualization of micromobility is still missing. Existing definitions are largely vehicle-centric: either listing modes or detailing vehicle characteristics. This paper addresses this gap by developing a ‘beyond vehicles’, multi-dimensional conceptualization of micromobility, accompanied by a novel socio-technical definition. Through a review of related concepts, combined with an analysis of the use and definitions of the term micromobility in publications, this study establishes a new conceptualization of micromobility. It incorporates human, social, and cultural dimensions, considers environmental, economic, infrastructure, vehicle technology, regulatory and policy aspects, and considerations for public health. Our definition of micromobility encompasses a wide range of mobility options typically used for shorter trips and manoeuvrable by an individual without motor assistance, at least for short distances. These modes are characterized by their ‘micro’ attributes, including low energy demand, environmental impact, and road space use relative to automobility. The conceptualization incorporates a range of micromobility modes, including fully human-powered (including walking), partially motor-assisted, and fully powered options. These modes typically operate at speeds not exceeding 25 to 32 kilometres per hour (or 45 km/h for faster options), weigh (typically substantially) below 350 kilograms and often yield significant (public) health benefits. Trip length is generally less than 15 kilometres, and daily distances under 80 kilometres. Importantly, our definition includes the practices, policies, cultures, and infrastructures that emerge around the use of micromobility options and shape their uptake. This proposed conceptualization significantly broadens the prevailing vehicle-focus in micromobility debates towards a socio-technical perspective. Embracing a widely accepted conceptualisation of micromobility would offer several advantages, including robust design standards, legislation, and evaluation metrics and methods. Additionally, this paper highlights the pivotal role micromobilities can play in transcending the limitations of automobility, towards more sustainable and equitable mobility futures.

Modal testing is a common step in aerostructure design, serving to validate the predicted natural frequencies and mode shapes obtained through computational methods. The strategic placement of sensors during testing is crucial to accurately measuring the intended natural frequencies. However, conventional methodologies for sensor placement are often time-consuming and involve iterative processes. This study explores the potential of machine learning techniques to enhance sensor selection methodologies. Three machine learning-based approaches are introduced and assessed, comparing their efficiency with established techniques. The evaluation of these methodologies is conducted using a numerical model of a beam to simulate real-world scenarios. The results offer insights into the efficacy of machine learning in optimizing sensor placement, presenting an innovative perspective on enhancing the efficiency and precision of modal testing procedures in aerostructure design.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Mineral surfaces have been demonstrated to play a central role in prebiotic reaction, which are supposed to be at the basis of the origin of life. Among the various molecules proposed as precursors for these reactions, one of the most interesting is formamide. Formamide has been shown to be a pluripotent molecule, generating a wide distribution of relevant pre-biotic products. In particular, the outcomes of its reactivity are strongly related to the presence of mineral phases, acting as catalysts toward specific reaction pathways. Even if the mineral-products relationship has been deeply studied for a large pool of materials, the fundamental description of the formamide reactivity over the mineral surface at a microscopic level is missing in the literature. In particular, a key step of formamide chemistry at surfaces is its adsorption on the available interaction sites. This report aims to investigate the adsorption of formamide over a well-defined amorphous silica, chosen as model mineral surface. An experimental IR investigation of formamide adsorption has been carried out and its outcomes have been interpreted on the basis of first principles simulation of the process adopting a realistic model of the amorphous silica.

Machine learning approaches are currently used to understand or model complex physical systems. In general, a substantial number of samples must be collected to create a model with reliable results. However, collecting numerous data is often relatively time-consuming or expensive. Moreover, the problems of industrial interest tend to be more and more complex and depending on a high number of parameters. High dimensional problems intrinsically involve the need of large data amount through the curse of dimensionality. That is why, new approaches based on smart sampling techniques are investigated to minimize the number of samples to be given to train the model, such as Active Learning methods. Here, we propose a technique based on a combination of Fisher information matrix and of Sparse Proper Generalized Decomposition that enables the definition of a new Active Learning informativeness criterion in high dimensions. We provide examples proving the performances of this technique on a theoretical 5D polynomial function and on an industrial crash simulation application. The results prove that the proposed strategy over-perform the usual ones.

Pipefishes (Family Syngnathidae) are representative fishes in many European coastal areas asso-ciated with vegetal assemblages and other shallow habitats. The polyandrous pipefishes Syngnathus abaster and S. acus co-occur in Metruk Tuzla (Bargilya Wetland, Aegean Sea, Turkey), a protected but threatened wetland due to anthropogenic disturbances. Both species were sam-pled during the breeding season (April-2018 and June-2019) for the assessment of growth and trophic features revealed from stable isotope profiles (δ13C and δ15N) and gut content. Both species showed positive allometric growth, with similar length-weight relationships. The isotope approach indicated that both species occupy similar trophic niches, with mean δ13C and δ15N values of -17.0 ± 1.2 ‰ for δ13C and 13.2 ± 0.6 ‰ for δ15N in S. abaster, and -17.3 ± 1.2 ‰ for δ13C and 13.3 ± 0.7 ‰ for δ15N in S. acus. The niche area for all sex types (undifferentiated specimens, males and females) in S. acus was slightly broader than in S. abaster. The simulation analysis of the trophic position (TP) in both species agreed with the isotopic assessment (TP = 3.67 ± 0.61 in S. abaster and 3.46 ± 0.66 in S. acus). Despite the high trophic resemblance between S. abaster and S. acus, the gut content assessment revealed the large contribution of copepods (especially Calanipeda aquaedulcis) to the dietary regime in both pipefishes. However, while the diet in S. abaster seemed to be almost monospecific, cladocerans were also an important resource in S. acus. Hence, we suggest that potential inter-specific competition for dietary resources would be minimized likely due to the occupancy of different microhabitats, a hypothesis that needs to be confirmed by further research.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/ml and/or Gleason score ≥8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes / lymph node metastases outside the established node template in high-risk PCa.

Chest X-ray (CXR) is the first tool globally employed to detect cardiopulmonary pathologies. These acquisitions are highly affected by scattered photons due to the large field-of-view required. Scatter in CXRs introduces background in the images, which reduces their contrast. We developed three deep learning-based models to estimate and correct the scatter contribution to CXRs. We used a Monte Carlo (MC) ray-tracing model to simulate CXRs from human models obtained from CT scans using different configurations (depending on the availability of dual-energy acquisitions). The simulated CXRs contained the separated contribution of direct and scattered X-rays in the detector. These simulated datasets were then used as the reference for the supervised training of several NN. Three NN models (single and dual energy) were trained with the MultiResUNet architecture. The performance of the NN models was evaluated on CXRs obtained with the MC code from chest CTs of patients affected by COVID-19. The results showed that the NN models were able to estimate and correct the scatter contribution to CXRs with an error &lt;5%, being robust to variations in the simulation setup and improving the contrast in soft tissue. The single-energy model was tested with real CXRs, providing robust estimations of the scatter-corrected CXRs.

The present research intents to study the evolution of the skin fatty acids and physiological disorders through cold storage in ‘Golden Delicious’ apples treated with 1-MCP and calcium. Harvested fruit were treated with calcium chloride (Ca), 1-MCP (MCP), Ca+MCP or no treatment (control) then subjected to cold storage at 0.5 ºC for 6 months. Fatty acids composition, Malondialdehyde (MDA) and the physiological disorders bitter pit (BP), superficial scald and diffuse skin browning (DSB) were measured at harvest and after storage plus 7 days shelf-life at room temperature ≈22 ºC. Palmitic acid decreased and linoleic acid increased through time, while oleic and stearic acids had few changes. Unsaturated/saturated fatty acids and MDA increased through time, despite Ca and Ca+MCP were related to lower MDA and lower BP and rotten fruit, after cold storage and shelf-life. In those treatments, the unsaturated/saturated fatty acids were higher, mainly due to higher linoleic acid and lower palmitic acids. Further research is needed to clarify the changes in membrane properties and the effect of some treatments in response to chilling injury through storage.

Meat-based diets are still the norm and vegans and vegetarians represent only a small minority of the population. A transition respectively behavioural change towards a diet with less meat can only occur with the adoption of a positive attitude towards dietary changes based on reasons and motivations. The main aim of this study is to validate the so-called meat attachment scale (MEAS) for Germany in order to analyse if this construct is a barrier towards a diet with less meat in this country. The findings show that the MEAS can be applied in Germany and a similar structure as reported for Spain and other countries could be found. Furthermore, a correlation analysis demonstrated that food neophobia and MEAS are not correlated with each other. That is, that meat attachment represents an independent and single predictor for trust in food (processing) technologies as e.g. plant-based proteins or cultured meat.

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

The yeast Saccharomyces cerevisiae is widely used in food and nonfood industries. During industrial fermentations yeast are exposed to fluctuations in oxygen concentration, osmotic pressure, pH, ethanol concentration, nutrient availability and temperature. Fermentation performance depends on the ability of different yeast strains to adapt to these changes. Suboptimal growth conditions trigger responses to these external stimuli to allow cellular homeostasis to be maintained. Stress-specific signaling pathways are activated to coordinate changes in tran-scription, translation, protein function, and metabolic fluxes while a transient arrest of growth and cell cycle progression occur. cAMP-PKA, HOG-MAPK and CWI signalling pathways are signal transduction pathways turned on during stress re-sponse. Comprehension of the mechanisms involved in the responses and in the adaptation to these stresses during fermentation is key to improving this industrial process. The scope of this review is to outline the advancement of knowledge about the cAMP-PKA signalling and the crosstalk of this pathway with the CWI and HOG-MAPK cascades in response to the environmental challenges heat and hy-perosmotic stress.

An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. P ≤ 0.05 was con-sidered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From 101 patients that were followed up, smokers had longer treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) is lower than the WHO threshold standard with a high proportion of patients lost to follow-up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

With a low rate of new building construction and insufficient rate of existing building renovation, there is the need for stepping up the pace of building renovation with ambitious performance targets to achieve EU climate change policies. However, effective technologies alone cannot solve the low renovation rate of existing buildings in Europe that is hindering the reaching of EU-wide targets. A workshop was held at the Sustainable Place Conference 2018 to present successful experiences with an integrative approach from H2020 innovation actions (4RinEU, P2ENDURE, Pro-GET-OnE, MORE-CONNECT) aiming at improving building energy performance through deep renovation. This article presents the outcomes of the joint workshop and interactive discussion, by focusing on the different technical, financial and social added values, barriers and challenges in building renovation as well as on the identification of open questions to address future innovation opportunities.

A numerical mechanism connecting ice algal ecodynamics with the buildup of organic macromolecules is tested within modeled pan-Arctic brine channels. The simulations take place offline in a reduced representation of sea ice geochemistry. Physical driver quantities derive from the global sea ice code CICE, including snow cover, thickness and internal temperature. The framework is averaged over ten boreal biogeographic zones. Computed nutrient-light-salt limited algal growth supports grazing, mortality and carbon flow. Vertical transport is diffusive but responds to pore structure. Simulated bottom layer chlorophyll maxima are reasonable, though delayed by about a month relative to observations due to uncertainties in snow variability. Upper level biota arise intermittently during flooding events. Macromolecular concentrations are tracked as proxy proteins, polysaccharides, lipids and refractory humics. The fresh biopolymers undergo succession and removal by bacteria. Baseline organics enter solely through cell disruption, so that the internal carbon content is initially biased low. By including exudation, agreement with dissolved organic or individual biopolymer data is achieved given strong release coupled to light intensity. Detrital carbon then reaches hundreds of micromolar, sufficient to support structural changes to the ice matrix.

Gold nanoclusters (AuNCs) with fluorescence in the Near Infrared (NIR) by both one- and two-photon electronic excitation were incorporated in mesoporous silica nanoparticles (MSNs) using a novel one-pot synthesis procedure where the condensation polymerization of alkoxysilane monomers in the presence of the AuNCs and a surfactant produce hybrid MSNs of 49 nm diameter. This method was further developed to prepare 30 nm diameter nanocomposite particles with simultaneous NIR fluorescence and superparamagnetic properties, with a core composed of superparamagnetic manganese ferrite nanoparticles (MnFe2O4) coated with a thin silica layer, and a shell of mesoporous silica decorated with AuNCs. The nanocomposite particles feature NIR-photoluminescence with 0.6% quantum yield and large Stokes shift (290 nm), and superparamagnetic response at 300 K, with a saturation magnetization of 13.4 emu g-1. The conjugation of NIR photoluminescence and superparamagnetic properties in the biocompatible nanocomposite has high potential for application in multimodal bioimaging.

The concept of innovation ecosystems brings to light a whole set of stakeholders that face the entire set of barriers to making new technologies change people´s lives. This research aimed to understand and analyze the innovation ecosystem in organic and agroecological production in the Federal District, Brazil, and its directly influenced area. A questionnaire was applied to 27 institutions identified as the backbone of the innovation ecosystem. The Gephi 0.10.1 software and the Force Atlas 2 network algorithm set up the relationship network. We verified a certain misalignment between expected roles and functions performed by 66% of the stakeholders. Low integration and dispersed relationships in the network were observed with a misalignment around the innovation concept in organic food production. This arrangement of the ecosystem is compatible with the initial stage, in which stakeholders and resources would be spread out and demobilized. Although shared governance is the most effective for an innovation ecosystem, the analyzed ecosystem demands centralized governance with a leading organization. Strengthening strategies were proposed to (i) define leadership, (ii) define roles or competencies, and (iii) strengthen community attributes.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Sperm DNA integrity and chromatin status serve as pivotal indicators of sperm quality, given their in-tricate link to sperm function, embryo development, and overall fertility. Defects in chromatin com-paction, which are often associated with compromised protamine content, can lead to damaged DNA strands. In this study, chromatin status and possible correlation with DNA damage was assessed in males of three mouse species: Mus musculus, M. spretus and M. spicilegus. We employed various staining methods, including aniline blue, methylene blue (Diff-Quik), toluidine blue and chromomy-cin A3, to assess chromatin compaction in cauda epididymal sperm. Samples were also analyzed by the sperm chromatin structure assay (SCSA) to estimate DNA fragmentation (%tDFI, %HDS). Analyses were carried out on freshly collected sperm and cells incubated for 3 h in a Hepes-buffered modified Tyrode's medium simulating conditions of the female reproductive tract. Notably, the analysis of chromatin status yielded minimal abnormal values across all three species, employing diverse meth-odologies. SCSA analyses revealed distinct variations in %tDFI between species. Following sperm incubation, the percentages of sperm stained with methylene blue exhibited differences among the species and were significantly correlated to the DNA fragmentation index. HDS demonstrated correla-tions with the percentages of sperm stained by aniline blue, methylene blue and chromomycin A3. Overall, chromatin compaction was high across all species, with limited differences among them. The relationship between chromatin status and DNA integrity appeared to be related to levels of sperm competition among species.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Benzaldehyde and its derivatives are used as food supplements, due to their properties as anti-oxidants and mainly as organoleptic substances. The degradation of these aldehydes produces benzoic acid and benzyl alcohol derivatives, both of which present high toxicity levels. On the other hand, peroxynitrite acts as an oxidizing agent, thus strategies for its production control during food processing could help to improve food quality parameters such as taste, colour and functional properties. Therefore, the control of these degradative oxidation processes is of great interest to the food industry. In order to know in depth this problem, the present article has fo-cused on the kinetic study of the oxidation of aldehydes by peroxynitrite. The proposed mecha-nism justifies all the experimental results, passing through three competitive pathways were per-oxynitrite acts as a radical, nucleophilic or oxidant species. The possible increase of toxic prod-ucts was analyzed.

Single-Anastomosis Duodeno-Ileal bypass with Sleeve Gastrectomy (SADI-S) is a modification of the duodenal switch in which only one anastomosis is performed, with a longer common limb and an expected less malabsorptive effect. The present study analyzes presentation and treatment of malnutrition after SADI-S. 258 consecutive patients undergoing SADI-S between May 2007 and September 2017 were included. The common limb length was 200 cm in 50 cases, 250 cm in 156 and 300 in 52. 30 patients were admitted for severe hypoalbuminemia and 16 patients were submitted to revisional surgery and constitute the series of our study. Mean weight before reoperation was 57 kg and mean body mass index (BMI) was 21 kg/m2. Mean number of daily bowel movements was 5,6. Mean time to reoperation was 56 months. Revisional surgery consisted mainly in elongation of the common limb. Mean weight regain was 14 kg and mean final BMI was 26 kg/m2. Daily bowel movements were decreased to 1,3. Factors related to hypoalbuminemia were hypertension, poor controlled diabetes, age over 55 years and a shorter common limb. Although SADI-S is expected to be less malabsorptive than previous biliopancreatic diversions, caution has to be taken with selected patients to avoid postoperative malnutrition.

The Mediterranean diet represents one of the most studied dietary patterns, however, there is no single tool for measuring the grade of adherence and no single criteria to adapting these indices to pregnant women. We characterized the adherence to the Mediterranean diet (MDA) of pregnant women participating in the NELA cohort and identified the sociodemographic determinants and lifestyle habits associated with a higher risk of a low MDA. Maternal diet during gestation was assessed by a validated Food Frequency Questionnaire (FFQ) (n=665). We estimated Relative Mediterranean Diet score (rMED), Alternative Mediterranean Diet score (aMED) and Alternate Healthy Index-2010 (AHEI-2010). Multivariate regression models were performed to identify the sociodemographic and lifestyle factors associated to each index. Mothers with lower age and more previous deliveries had a greater probability of low MDA (P &lt;0.05). Only, for aMED index, mothers with university education and / or who practiced 2 or more hours per week sport activities had a lower probability of a low MDA (P &lt;0.01). These results may be useful in order to design intervention strategies and dietary recommendation for pregnant women.

The incidence of hepatocellular carcinoma (HCC) is increasing and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinical available treatments have dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients showing a durable treatment benefit over time, and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with non-viral etiologies, such non-alcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers informative of the best treatment approach are required actions to improve patient survival. Numerous evidence indicated non-coding RNAs (ncRNAs) as pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

This research investigates the difference on the products obtained through two hydrothermal carbonization treatments. Our aim is to synthesize metal-free, carbon-based catalysts for the Oxygen Reduction Reaction (ORR) to serve as efficient and cost-effective alternatives to plati-num-based catalysts. Catalysts synthesized using the traditional hydrothermal approach exhibit a higher electrocatalytic activity for ORR in alkaline media, despite a more energy-intensive pro-duction process. The superior performance is attributed to differences in particle morphology and to the chemical composition of the particle surfaces. The presence of functional groups on the surfaces of catalysts obtained via traditional approach significantly enhances ORR activity by fa-cilitating deprotonation reactions in an alkaline environment. Our research aims to be a reference for future investigations, shifting the focus to the fine-tuning of surface chemical compositions and morphologies of metal-free catalysts to enhance ORR activity.

Ceruminous gland tumours are rare injuries of the external auditory canal (EAC). This tumor, even if considered a slow-growing carcinoma, has high rate of perineural invasion and metastasis. For this reason, it must be promptly diagnosed, then it must be treated with aggressive surgery combined with postoperative radiation. The present case report is about a case of an adenoid cystic carcinoma arising the external auditory canal of 46 years old female patient, who complained hypoacusis and pain. The profile of medical liability is substantiated on the delayed diagnosis when the lately observed tumor progression by the invasion of both surrounding bone and vascular structures.

Machine Learning (ML) methods have become important to enhance the performance of decision-support predictive models. However, class imbalance is one of the main challenges for developing ML models, because it limits the generalization of these models, and biases the learning algorithms. In this paper, we consider oversampling methods for generating synthetic categorical clinical data aiming to improve the predictive performance in ML models, and the identification of risk factors for cardiovascular diseases (CVDs). We performed a comparative study of several categorical synthetic data generation methods, including Generative Adversarial Networks (GANs). Then, we assessed the impact of combining oversampling strategies and linear and nonlinear supervised ML methods. Lastly, we conducted a post-hoc model interpretability based on the importance of the risk factors. Experimental results show the potential of GAN-based models for generating high-quality categorical synthetic data, yielding probability mass functions that are highly close to real data, maintaining relevant insights, and contributing to increase the predictive performance. The GAN-based model and a linear classifier outperforms other oversampling techniques, improving 2\% the area under the curve. These results demonstrate the capability of synthetic data to help both in determining risk factors and building models for CVD prediction.

(1) Background: To determine the diagnostic accuracy that optical coherence tomography (OCT) can add to fundus photography (FP) in assessing the condition of the retinal posterior pole; (2) Methods: Two blocks of analysis: at first, the posterior pole of each eye was examined using FP non-mydriatic imaging device. Secondly: OCT was used in addition to FP. After consolidating specific diagnostic criteria, the assessments were evaluated by two blinded independent investigation groups (by optometrists, and by ophthalmologists who was considered the gold standard); (3) Results: We calculated the diagnostic accuracy of FP compared to OCT and found that both had similar sensitivity, FP had slightly higher specificity, (p-value: 0.01) and OCT had a higher kappa coefficient 0.50 (95%CI: 0.46-0.55) vs 0.39 (95%CI: 0.34-0.45) of FP; (4) Conclusions: Based on the premise that the role of the optometrist in Spain is not to diagnose but to detect lesions and refer patients to an ophthalmologist, the results of this study support the use of OCT, that it provided gradable images in almost all examined eyes (97.5%), compared to FP (73.5%). However, the optometrist need a detailed and standardized guide in order to evaluate according to the ophthalmologist's criteria.

The chemical synthesis of silver nanoparticles (Ag-NPs) by using an environmentally friendly methodology for their preparation is presented. Thus, considering that plants possess components that can act as reducing agents and stabilizers in the nanoparticles production, in this work, the synthesis of Ag-NPs by using a solution of grape waste extract as reducing and capping agent is studied. First, the total polyphenols content and reducing sugars in extracts produced at different conditions are characterized. After that, Ag-NPs are synthesized regarding the interaction of Ag ions (from silver nitrate) and the grape waste extract. The effect of temperature, contact time, extract/metal solution volume ratio and pH solution in the synthesis of metal nanoparticles are studied too. Different sets of nanoparticle samples are fully characterized by means of Electron Microscopy coupled with Energy Dispersive X-Ray for qualitative chemical identification. Ag-NPs with an average diameter of 27.7 ± 0.6 nm are selected to proof their suitability for sensing purposes. Thus, screen-printed electrodes modified with Ag-NPs are tested for the simultaneous voltammetric stripping determination of Pb(II) and Cd(II). Results indicate good reproducibility, sensitivity and limits of detection around 2.7 µg L⁻¹ for both metal ions.

The synthesis of four samples of new polyurethanes was evaluated by changing the ratio of the diol monomers used, poly(propylene glycol) (PPG) and D-isosorbide, in the presence of aliphatic isocyanates such as the isophorone diisocyanate (IPDI) and 4,4′-methylenebis(cyclohexyl isocyanate) (HMDI). The thermal properties of the four polymers obtained were determined by DSC, exhibiting Tg values in the range 55-70 ºC, and their molecular structure characterized by FTIR, 1H and 13C NMR spectroscopies. The diffusion coefficients of these polymers in solution were measured by the Pulse Gradient Spin Echo (PGSE) NMR method, enabling the calculation of the corresponding hydrodynamic radii in diluted solution (1.62–2.65 nm). The molecular weights were determined by GPC/SEC and compared with the values determined by quantitative 13C NMR analysis. Finally, the biocompatibility of the polyurethanes was assessed using the HaCaT keratinocyte cell line by the MTT reduction assay method showing values superior to 70% cell viability.

Introduction: Unlike cigarette smoking, secondhand smoke (SHS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. We systematically reviewed the association between SHS and the risk of onset and/or progression of MS.Methods: We systematically screened MEDLINE/PUBMED, Science Direct, LILACs, and SCIELO searching for publications between January 1st , 2010, and July 5, 2021 with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. An 11-year filter was applied from 2010 to 2021. Results: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of SHS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between SHS and MS development, and one study that did not find a significant association between SHS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between SHS and MS. Seven observational studies reported higher odds of MS onset when associated with SHS. Four observational studies did not show a relationship between SHS and MS onset or progression.Discussion: Most articles showed a positive association between SHS exposure and the risk of developing MS. On the other hand, an association between SHS and a higher risk for MS progression could not be established.

The aquaculture sector has become increasingly reliant on soybean meal (SBM) and soy-derived proteins, because of their large abundance, low price and favorable amino acid profile. However, for Atlantic salmon, a major aquaculture species, the inclusion of soybean meal, and soy protein concentrate (SPC) in certain combinations has adverse impacts on its gut health and welfare. This study evaluated two enhanced SBM targeting improved gut health for inclusion in freshwater phase salmon diets, enzyme pre-treatment (ETS) and addition of fructose oligosaccharide (USP), respectively in comparison to untreated soybean meal (US) and fish meal (FM). The impact on growth performance, gut microbiome, and behaviors relevant to welfare was investigated. Both enhancements of SBM were found to support comparable growth performance to FM. Both targeted treatments altered the gut microbiome community. Fish fed SBM showed a tendency for more reactive behavior compared to those fed the FM-based control. All fish had a similarly low response to elicited stress, although ETS fed fish responded more actively than those fed the US diet. SBM fed fish also had lower repeatability of behavior, which may have implications for welfare. Both enhancements provide a promising basis to optimize the application of this widely used protein source.

Traditional medicine is one of the main bases for studying and discovering natural sources of phytometabolites with antiviral properties. This research aims to demonstrate that the medicinal plants used as a treatment of viral diseases in the La Libertad region have, in fact, antiviral ac-tivity. The study evaluated the ethnobotany of the 8 most widely used medicinal plants in the region (Azadirachta indica A. Juss. “paraíso”, Caesalpinia spinosa (Molina) Kuntze “tara”, Citrus limon (L.) Osbeck “limón”, Clinopodium pulchellum (Kunth) Govaerts “panizara”, Cordia lutea Lam. “overo”, Ocimum basilicum L. “albahaca”, Schinus molle L. “molle”, and Taraxacum campylodes G.E. Haglund “diente de león”). The phytometabolites responsible for the antiviral activity were identified by LC-MS and evaluated in silico against the viral proteins NS2B/NS3 (DENV-2), NS5B (HCV), and ICP27 (HSV-1) using molecular docking in Autodock Vina and UCSF Chimera. The presence of five polyphenols (chlorogenic acid, gallic acid, caffeic acid, rosmarinic acid, and rutin) was found and, in the in silico test, the antiviral activity of chlorogenic acid stood out against DENV-2 and HCV, rutin against HCV and HSV-1, rosmarinic acid against DENV-2 and HCV. Therefore, it is verified that the medicinal plants studied have antiviral activity, which supports their use in traditional medicine

Marseille-Q4369 is a strain that we isolated from human healthy skin and characterized by taxono-genomic approach. Marseille-Q4369 exhibited 99.80% 16S rRNA sequence similarity with Agrococcus pavilionensisT the phylogenetically closest bacterium with standing in nomenclature. Furthermore, digital DNA–DNA hybridization revealed a maximum identity similarity of only 52.4% and an OrthoANI parameter provided a value of 93.63% between the novel organism and Agrococcus pavilionensisT. Marseille-Q4369 was observed to be a yellowish-pigmented, Gram-positive, coccoïd, facultative aerobic bacterium, and belonging to the Microbacteriaceae family. The major fatty acids detected are 12-methyl-tetradecanoic acid (66%), 14-methyl-hexadecanoic acid (24%) followed by 13-methyl-tetradecanoic acid (5%). The genome size of strain Marseille-Q4369 was 2,737,735-bp long with a 72,27 % G+C content. Taken altogether, these results confirm the status of this strain as a new member of the Agrococcus genus for which the name of Agrococcus massiliensis is proposed (=CSUR-Q4369 = DSM112404).

Reservoirs are characterized by accumulation of sediments where micropollutants may concentrate, with potential toxic effects on downstream river ecosystems. However, sediment management such as flushing is needed to maintain storage capacity. Climate change is expected to increase sediment loads, but potential effects on their quality are scarcely known. In this context, sediment contamination by trace elements (As, Cd, Cr, Cu, Hg, Ni, Pb, Zn) and organics (PAHs, PCBs, C>12) was analyzed in 20 reservoirs located in Italian Central Alps. A strong As and a moderate Cd, Hg and Pb enrichment was emphasized by Igeo, with potential ecotoxicological risk according to PEC quotients. Siltation, granulometry, total organic carbon (TOC) and altitude resulted as the main drivers governing pollutant concentrations in sediments. According to climate change models, expected increase of rainfall erosivity will enhance soil erosion and consequently the sediment flow to reservoirs, potentially increasing coarse grain fractions and thus potentially diluting pollutants. Conversely, increased weathering may enhance metal fluxes to reservoirs. Increased vegetation cover will potentially result in higher TOC concentrations, which may contrast contaminant bioavailability and thus toxicity. Our results may provide elements for a proper management of contaminated sediments in a climate change scenario aiming at preserving water quality and ecosystem functioning.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regula-tion of the microtubule cytoskeleton and may thus represent valuable molecular markers contrib-uting to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B, KIFC1, AURKB, KIF2C, GTSE1, KIF15, KIF11, RACGAP1, STMN1) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B) are overexpressed by more than 10-fold in tumor samples and four of them (KIF11, AURKB, TPX2 and KIFC1) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (MAST4, MAPT and MTUS1) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Together our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer.

Tuberculosis (TB) is still a worldwide major health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study we have analysed CT images collected from cynomolgus and rhesus macaques, following exposure to ultra-low dose Mycobacterium tuberculosis (Mtb) aerosols, and monitored them for 16 weeks to evaluate the impact of prior intradermal or inhaled BCG-vaccination on the progression of lung disease. All lesions found (2553) have been classified according to their size and we have subclassified small micronodules (<4.4 mm) as ‘isolated’, or as ‘daughter’ when they are in contact with consolidation (described as lesions ≥ 4.5 mm). Our data links the higher capacity to contain Mtb infection in cynomolgus with the reduced incidence of daughter micronodules, thus avoiding the development of consolidated lesions and their consequent enlargement and evolution to cavitation. In the case of rhesus, intradermal vaccination has a higher capacity to reduce the formation of daughter. This study supports the ‘Bubble Model’ defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcome in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

LDAS-Monde, an offline land data assimilation system with global capacity, is applied over the CONtiguous US (CONUS) domain to enhance monitoring accuracy for water and energy states and fluxes. LDAS-Monde ingests satellite-derived Surface Soil Moisture (SSM) and Leaf Area Index (LAI) estimates to constrain the Interactions between Soil, Biosphere, and Atmosphere (ISBA) Land Surface Model (LSM) coupled with the CNRM (Centre National de Recherches Météorologiques) version of the Total Runoff Integrating Pathways (CTRIP) continental hydrological system (ISBA-CTRIP). LDAS-Monde is forced by the ERA-5 atmospheric reanalysis from the European Center For Medium Range Weather Forecast (ECMWF) from 2010 to 2016 leading to a 7-yr, quarter degree spatial resolution offline reanalysis of Land Surface Variables (LSVs) over CONUS. The impact of assimilating LAI and SSM into LDAS-Monde is assessed over North America, by comparison to satellite-driven model estimates of land evapotranspiration from the Global Land Evaporation Amsterdam Model (GLEAM) project, and upscaled ground-based observations of gross primary productivity from the FLUXCOM project. Also, taking advantage of the relatively dense data networks over CONUS, we also evaluate the impact of the assimilation against in-situ measurements of soil moisture from the USCRN network (US Climate Reference Network) are used in the evaluation, together with river discharges from the United States Geophysical Survey (USGS) and the Global Runoff Data Centre (GRDC). Those data sets highlight the added value of assimilating satellite derived observations compared to an open-loop simulation (i.e. no assimilation). It is shown that LDAS-Monde has the ability not only to monitor land surface variables but also to forecast them, by providing improved initial conditions which impacts persist through time. LDAS-Monde reanalysis has a potential to be used to monitor extreme events like agricultural drought, also. Finally, limitations related to LDAS-Monde and current satellite-derived observations are exposed as well as several insights on how to use alternative datasets to analyze soil moisture and vegetation state.

A right frontoparietal neoplastic lesion was found in a young-aged patient with analgesic refractory headache. Surgical resection was performed, and the pathologist analysis turned out a cellular ependymoma with signs of anaplasia. In the follow-up, a MRI showed a suspicious lesion, so a [18F]Fluorocholine PET/CT was performed. An increased uptake was described in the right parietal region on the margin of residual cystic lesion. The patient got a complete resection which was confirmed later by MR. In the pathology analysis, a focally congestive cerebral parenchyma with a central histiocytic reaction to foreign body area was described. Foreign body reaction in brain tissue is a very rare immune response that has not been well studied. Haemostatic material has been reported as a possible trigger of this response in other organs and could be detected by [18F]FDG PET/CT. Following the experience of the current case report, [18F]Fluorocholine PET/CT could also show a false positive related to foreign body reaction.

Recent dissection studies resulted in the introduction of the term “chiasma antebrachii”, which represents an intersection of the flexor digitorum superficialis (FDS) tendons for digit 2 and 3 in the distal third of the forearm. This retrospective investigation aimed to provide an MRI-based morphologic analysis of the chiasma antebrachii. In 89 patients (41 women, 39.3±21.3 years), MRI examinations of the forearm (2010–2021) were reviewed by two radiologists, who evaluated all studies for the presence and length of the chiasma as well as its distance from the distal radioulnar and elbow joint. The chiasma antebrachii was identified in the distal third of the forearm in 88 patients (98.9%), while one intersection was located more proximally in the middle part. The chiasma had a median length of 28 mm (interquartile range: 24–35 mm). Its distances to the distal radioulnar and elbow joint were 16 mm (8–25 mm) and 215 mm (187–227 mm), respectively. T1-weighted post-contrast sequences were found to be superior to T2- or proton density-weighted sequences in 71 cases (79.8%). Concluding, the chiasma antebrachii is part of the standard FDS anatomy. Knowledge of its morphology is important, e.g. in targeted injections of therapeutics or reconstructive surgery.

Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (&lt; 2,500 m) and high altitude (&gt;2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

We studied the efficacy of mesenchymal stem cells (MSC), either alone or associated with dapsone (DAP) in the treatment of dermonecrotic wounds caused by Loxosceles laeta spider venom. Twenty-five male adult rabbits were distributed into five groups, of which four groups received an intradermal injection of 20 μg of L. laeta venom and only one received ultrapure water (negative control). After 4 hours, each group that received venom, was treated with MSC, DAP, MSC + DAP and Phosphate-buffered saline – PBS (positive control). Photographic records were made for analysis of the wound area evolution by morphometry. Twelve days after treatment, the skin samples around the lesion were removed for subsequent histological analysis. Concerning the rate of wound contraction, we observed that DAP showed the best percentage of contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS group. Histopathological analysis showed diminished tissue lesion and less intense inflammation in MSCs and DAP groups. This could indicated potential use of stem cells in regenerative therapies after loxoscelic accidents.

Anemonia viridis is an abundant and widely-distributed temperate sea anemone that can form dense congregations of individuals. Despite the potential severity of its sting, few detailed cases have been reported. We report a case of a severe toxic reaction following an A. viridis sting in a 35-year-old oceanographer. She developed severe pain, itching, redness and burning sensation, which worsened one week after treatment with anti-inflammatories, antihistamines and corticosteroids. Prompted by this event, and due to the insufficient risk prevention, lack of training for marine-environment users and lack of research into sting-specific first-aid protocols, we evaluated the cnidocyst response to five different compounds commonly recommended as rinse solutions in first-aid protocols (seawater, vinegar, ammonia, baking soda and freshwater) by means of the Tentacle Solution Assay. Vinegar and ammonia triggered an immediate and massive cnidocyst discharge after their application and were classified as activator solutions. Baking soda and freshwater were also classified as activator solutions, although with a lower intensity of discharge. Only seawater was classified as a neutral solution and therefore recommended as a rinse solution after A. viridis sting, at least until an inhibitory solution is discovered.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23-72 participated in one of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

Climate change related increases in frequency and intensity of heatwaves affect viticulture, leading to losses in yield and grape quality. We assessed whether canopy architecture manipulation mitigates the effects of summer stress in a Mediterranean vineyard. Muscat of Alexandria grapevines were monitored during 2019-2020. Two canopy shoot positioning treatments were applied: Vertical shoot positioning (VSP); and Modulated shoot positioning (MSP), the west side upper foliage released to promote partial shoot leaning, shading the clusters. Clusters were sampled at pea size (PS), veraison (VER) and full maturation (FM). Measurements included rachis anatomy and hydraulic conductance, and aquaporins (AQP) and stress-related genes expression in cluster tissues. Results show significant seasonal and interannual differences in Kh and vascular anatomy. At VER, Krachis , Krachis+pedicels, and xylem diameter decreased but were unaffected by treatments. The Phloem/Xylem ratio was either increased (2019) or reduced (2020) in MSP, compared to VSP. Most AQP were down-regulated at FM in pedicels, and up-regulated at VER in pulp. A potential maturation shift in MSP was observed, confirmed by the up-regulation of several stress-related genes in all tissues. The study pinpoints the role of canopy architecture in berry water relations and stress response during ripening.

(1) Background: São Paulo, Brazil, exhibits high mortality rates from pediatric solid tumors. This study analyzed the survival trends of patients aged 0-19 diagnosed with the state's five most prevalent solid tumors between 2000-2022. (2) Methods: An epidemiological, descriptive study utilized data from the Oncocentro Foundation of São Paulo, classified according to the International Classification of Childhood Cancer. The time between the first consultation and diagnosis, between diagnosis and treatment initiation, and patient survival were assessed using the Pe-to-Peto test. (3) Results: Analysis involved 11,067 cases: 53.5% male, with 89.6% diagnosed via microscopic confirmation. Tumor distribution comprised 34.3% central nervous system, 21.1% bone, 18.6% soft tissue, 14.2% germ cell, and 11.9% retinoblastomas. Main treatments included surgery with chemotherapy (26.5%), surgery alone (20.5%), and chemotherapy alone (15.6%). The average time between consultation and diagnosis was 22.94 ± 69.93 days, significant for treatments and recurrences, except for germ cell tumors (p=0.0178). The time between diagnosis and treatment was 25.46 ± 39.71 days, not significant for germ cell tumor treatments (p=0.0793). (4) Conclusions: Survival curves varied among neoplasm groups, with patients experiencing delays beyond recommended times, despite advanced healthcare services in the state.

Some of the most recent advances in enzymatic glycosylation processes focused on the production of important bioactive compounds have been analyzed. The applicability of different enzymes such as glycosidases, glycosyltransferases, glycophosphorylases and glycosynthases have been de-scribed around the review article considering their advantages and disadvantages of these biocat-alysts in the stereoselective and regioselective synthesis of different types of glycosylated mole-cules, phenolic and aliphatic alcohols, oligosaccharides, polysaccharides, glycoderivatives, glyco-peptides and glycoproteins with a clear focus on food and pharmaceutical chemistry. Therefore, these approaches combining the use of different catalytic systems, the improvement of tools such as immobilization technology, or chemical or genetic modification to improve the synthesization in the glycosylation process could be a very useful tool in a continuous biotechnological advance.

The hygromycin B phosphotransferase gene from Escherichia coli and the pyrithiamine resistance gene from Aspergillus oryzae are two dominant selectable marker genes widely used to genetically manipulate several fungal species. Despite the recent development of CRISPR/Cas9 and marker-free systems, in vitro molecular tools to study Aspergillus fumigatus, a saprophytic fungus causing life threatening diseases in immunocompromised hosts, still rely extensively on the use of dominant selectable markers. The limited number of drug selectable markers is already a critical aspect, but the possibility that their introduction into a microorganism could induce enhanced virulence or undesired effects on metabolic behavior, constitutes another problem. In this context, here we demonstrate that the use of ptrA in A. fumigatus leads to secretion of a compound that allows recovery of thiamine auxotrophy. In this study we developed a simple modification of the two commonly used dominant markers in which the development of resistance can be controlled by the xylose-inducible promoter PxylP from Penicillium chrysogenum. This strategy provides an easy solution to avoid undesired side effects since the marker expression can be readily silenced when not required.

Background: Globally, about 3.5 billion people are affected by intestinal parasitic infections (IPIs). This study aimed to investigate the effects of IPIs on intestinal wall thickness and its potential association with hypertension in different genders. Methods: A total of 108 subjects, including 83 consecutive patients with symptomatic and laboratory-confirmed IPIs (male = 48; female = 35) and 25 healthy controls (male = 10; female = 15), were recruited. B-mode ultrasound grayscale and color images of the duodenum and colon were obtained with and without water contrast. Results: Patients with IPIs had a tendency towards greater duodenal wall thickness (DUOTHICK = 0.88 ± 0.73 cm) compared to controls (0.595 ± 0.089 cm), p = 0.056. Patients with IPIs also had significantly greater ascending colon wall thickness (ASCTHICK = 1.076 ± 0.29 cm) and descending colon wall thickness (DSCTHICK = 1.175 ± 0.366 cm) compared to controls (ASCTHICK = 0.6015 ± 0.1607 cm, DSCTHICK = 0.6223 ± 0.135 cm), p < 0.05. Men over 50 years had greater DSCTHICK (1.25 ± 0.434 cm) than post-menopausal women (0.986 ± 0.389 cm), p < 0.05. DSCTHICK significantly predicted diastolic blood pressure (β = -0.295, p < .05) and blood sodium level (β = -0.300, p < .05). Conclusion: We demonstrated the effects of IPIs on the intestinal microbiome causing intestinal wall cytoskeletal dysfunction, which led to the development of a "leaky gut syndrome."

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

Although the effect of thermal modification (TM) on teak wood color is well documented, a few studies were carried out in closed system processes, as well as it remains unclear the effect of different processes on the same material. This work aimed to verify the effect of closed and open system processes of TM on the color of fast-growing teak wood. Thermally modified wood was evaluated in a closed system at 160 °C (CS160) and in an open system at 185 °C and 210 °C (OS185 and OS210). We measured the moisture content (initial and final) of wood, and the corrected mass loss (CML). The chemical analyses encompassed the contents of alpha-cellulose, hemicelluloses, lignin, and extractives (total, in acetone and dichloromethane). Wood color was measured before and after TM according to the CIEL*a*b* color space. It was possible to achieve the same color using different processes of thermal modification (CS160 and OS210). TM reduced wood lightness (L*), red-green chromaticity coordinate (a*), and yellow-blue chromaticity coordinate (b*). L* and a* had the bigger and lower variations, respectively. The color of thermally modified wood was significantly changed, even at the mildest condition tested (OS185, 0.33% CML).

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

"Suero costeño" a type of sour cream, is a traditional dairy product made mainly in the Colombian Caribbean region and has a variety of uses. The objective was to characterize the physicochemical and rheological properties of “suero costeño” produced in department of Córdoba-Colombia. Samples of " suero costeño " were obtained from local producers, characterized physicochemically (protein, fat, crude fiber, moisture, ash, carbohydrates, chlorides, pH and acidity), and rheologically (stationary tests), adjusting their behavior to the power-law model. The results show great variability in the physicochemical characteristics of the “suero costeño” made by the different artisanal producers, classifying it as a full-fat sour cream or light sour cream, and values of protein, pH and acidity similar to similar traditional dairy products from other countries, such as Reindeer sour cream and Curd or cottage cheese. “Suero costeño” can be classified as a pseudoplastic fluid and depending on the raw materials used and the production process, some present thixotropy, which may be the product of interactions between proteins and fats, which cause changes in the internal structure. Due to this great variability in its physicochemical and rheological characteristics, it is necessary to standardize the process of producing to improve the marketing of this Colombian culinary product.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

The crystal structure of a polymorph of Glycyl-L-alanine HI.H2O was synthesized from chiral cyclic Glycyl-L-alanine dipeptide, known to show molecular flexibility in different environments. The space group is polar (P21) and therefore pyroelectricity and optical second harmonic generation properties are allowed by symmetry. We report a pyroelectric coefficient as high as 45 µC/m2K occurring at 345 K, one order of magnitude smaller than the semi-organic ferroelectric Triglycine Sulphate (TGS) crystal. Furthermore, the polymorph displays a nonlinear optical effective coefficient of 0.14 pm/V, around 14 times smaller than the value from a phase-matched inorganic Barium Borate (BBO) single crystal.

Dengue is one of the most important arboviruses worldwide, with currently approximately 2.5 billion people at risk of becoming infected, mainly in tropical countries. The present study evaluated the influence of climatic variables on the incidence of dengue fever in an endemic urban area. A time series study of cases was carried out with all confirmed cases of dengue fever in the municipality of Belo Horizonte from 2001 to 2021. The climatic explanatory variables were obtained from the National Institute of Meteorology. The analysis was performed using a generalized linear regression model with three scenarios: a no-lag model, 1-month lag model (1 month earlier) and 2-month lag model (2 months earlier). In the no-lag model, the maximum temperature was associated with an increase in the monthly incidence of dengue (IRR: 1.5). In the 1- and 2-month lag models, the monthly average temperature was associated with an increase in incidence (IRR: 1.9 in both). Our results suggest that temperature contributed to the increase in the incidence of dengue, and an increase of 1 °C could increase the incidence of the disease by approximately 90%. Thus, temperature monitoring can direct efforts towards prevention and control of the disease.