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Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level. Neutralizing antibodies are key to resolving viral infections and confer long-term protection. This work provides a detailed analysis of how murine and human sera neutralize a non-enveloped human virus, coxsackievirus B3, and how the virus can escape them.

RNA viruses have notoriously high mutation rates due to error-prone replication by their RNA polymerase. However, natural selection concentrates variability in a few key viral proteins. To test whether this stems from different mutation tolerance profiles among viral proteins, we measured the effect of >40,000 non-synonymous mutations across the full proteome of coxsackievirus B3 as well as >97% of all possible codon deletions in the nonstructural proteins. We find significant variation in mutational tolerance within and between individual viral proteins, which correlated with both general and protein-specific structural and functional attributes. Furthermore, mutational fitness effects remained stable across cell lines, suggesting selection pressures are mostly conserved across environments. In addition to providing a rich dataset for understanding virus biology and evolution, our results illustrate that incorporation of mutational tolerance data into druggable pocket discovery can aid in selecting targets with high barriers to drug resistance.

Nowadays, the potato is one of the most cultivated and consumed food crops in the world and, in recent years, its production has experienced a sharp increase. Its industrial processing generates several by-products that are wasted and cause economic and environmental problems. Among them, potato peel stands out, representing up to 10% of the total potato residues obtained in the processing. On the other hand, these wastes, in addition to presenting antioxidant compounds, are rich in interesting chemical compounds of great value in a biorefinery model. This review summarizes the main compounds present in potato skins as well as the most used and innovative extraction methods employed for their isolation, with special emphasis on the fractions with biological activities. In addition, a sustainable biorefinery proposal focused on obtaining high added-value products with potential applications in the pharmaceutical, food, nutraceutical, or cosmetic industries is included.

Crimean-Congo hemorrhagic fever (CCHF) is a viral infectious disease for which distribution of the main vector, Hyalomma spp. ticks, is expanding. We analyzed all 10 cases of CCHF diagnosed in Spain during 2013-2021; case-patient median age was 56.5 years, and 7 were men. We identified CCHF virus genotypes III and V. Six case-patients acquired the infection in urban areas. Sixty percent of patients were infected in summer and 40% in spring. Two patients met criteria for hemophagocytic syndrome. Seven patients survived. The epidemiologic pattern of CCHF in Spain is based on occasional cases with an elevated mortality rate. Genotype III and, to a less extent also genotype V, CCHF circulates in humans in a common geographic area in Spain. Those data suggest that the expansion pathways are complex and may change over time. Physicians should remain alert to the possibility of new CCHF cases.

The uncertain economic situation that was experienced because of the global financial crisis in 2008 and the exponential growth in the use of new technologies in different industries has caused some individuals to become entrepreneurs through the development of a variety of new skills. The main objective of this research paper is to discover what factors significantly determine the degree of fulfilment of expectations for entrepreneurs who have graduated from the incubator programme. Entrepreneurs may expect that a business incubator programme is a key element for their economic development and that it provides them with skills for good image and professional recognition. From the methodological point of view, a survey technique was conducted on 100 entrepreneurs who had already graduated from different business incubator programmes in Madrid, Spain. For the data exploration phase, an Exploratory Factor Analysis was used, which made it possible to identify 10 factors. With the Multiple Linear Regression analysis, these newly created and named factors were ordered by level of importance. The main findings show that most statistically significant factors consist of variables that are related to behaviour, attitude and hard skills (trained).In turn, results demonstrate that soft skills (innate) also play a certain role for fulfilling expectations for developing a successful company. Study confirms that continuous managerial training programmes for entrepreneurs in the twenty-first century are a substantial part for obtaining new skills, knowledge, insights, experiences, and change of behaviours and attitudes of different aspects needed for successful company leadership and management.

Randomized controlled trials have demonstrated mortality benefits for several medication classes in patients with heart failure (HF), especially with reduced ejection fraction (EF). However, the benefit of these traditional HF therapies in patients with HF from cardiac amyloidosis is unclear. our study aimed to evaluate the safety and efficacy of traditional HF therapies in patients with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF (HFmrEF). We conducted a single-center retrospective study. Patients were included if they were diagnosed with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF between January 2012 and 2022. The primary outcomes of interest were medication use patterns (for β blockers [BB], angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARBs], angiotensin receptor neprilysin inhibitors [ARNI], and mineralocorticoid receptor antagonists [MRAs]); potential medication side effects (symptomatic bradycardia, fatigue, hypotension, lightheadedness, and syncope); hospitalization; and death. The associations of BB, ACEI/ARB/ARNI, and MRA use with clinical outcomes were evaluated using Kaplan-Meier and Cox proportional hazards regression. A total of 82 patients met study criteria. At time of cardiac amyloidosis diagnosis, 63.4% were on a BB, 51.2% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. At last follow-up, 51.2% were on a BB, 35.4% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. There were no statistically significant differences in rates of potential medication side effects in patients on the medication class compared with those who were not. There was no association with hospitalization or mortality for baseline or follow-up BB, ACEI/ARB/ARNI, or MRA use. In conclusion, BBs, ACEI/ARB/ARNIs, and MRAs may be safely used in this population. However, their use does not appear to improve mortality or hospitalization.

This paper aims to unpack the relational dimension of place and placemaking by analysing how creative actions underpin relational values towards socio-spatial restoration in the sacrifice zone affecting the communities of Quintero and Puchuncaví (QPSZ) in Chile. Sacrifice zones are places permanently subject to environmental damage and lack of environmental regulation. For affected populations in environmentally degraded areas, creative actions such as murals, music, and street performances have become a way to re-establish connections both among humans, and between humans and the environment. To date, little has been theorized on this connection. With this in mind, we use network analysis to analyze which and how relational values are mobilized by artistic actions, and to examine ensuing socio-spatial transformations. Drawing insights from 35 interviews with activists, artists, and residents in QPSZ, we observed relational effects of arts, especially in creation processes, and in representations of local elements and life histories. The materiality of artistic practices raised as a force of placemaking, and so did artistic spaces as promoters of networking and social cohesion, essential for socio-spatial restoration. By bringing together insights from aesthetic politics, human geography, and relational values, this paper contributes to the emerging literature on art committed to tackling socio-environmental crises, and to political–ecological theories on the transformation of degraded areas.

In 2020, the Global Media Monitoring Project (GMMP) marked its silver anniversary by releasing its sixth report on the representation of women in the global media landscape, and in 2021, the NGO Plan International unveiled the tenth edition of its report “State of the World’s Girls: The Truth Gap”. The study focused on how misinformation impacts equal opportunities for girls, adolescents, and young women worldwide, and proposed strategies to combat the “truth gap”. These examples showcase the collective efforts made in recent decades by professionals, academia, institutions, NGOs, and activists to enhance the state of information globally. The aspiration is ambitious, aiming to make information more transparent, accessible, and inclusive, fostering equality, truth-seeking, and the visibility of women, young people, and rural populations. However, the findings from the GMMP reports, as well as the analysis conducted by Plan International and numerous other works, underscore that despite evident social changes worldwide—particularly in the educational, labor, and social realms for women—access to truthful and high-quality information remains elusive. Simultaneously, studies reveal a declining public trust, especially among young people, in traditional media, a shift to alternative information sources, and a deterioration in the quality benchmarks of the journalism profession. Journalism, a pursuit of truth from sources to the public, has historically been and should remain a pillar upholding democracy and freedom. This article employs a qualitative case study methodology to analyze the best practices proposed across various domains to safeguard information quality. Special attention is given to initiatives that aim to involve women and young people in the collective effort against misinformation.

To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence. We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0-4 years, 5-9 years, 10-14 years, and 15-19 years, respectively, and for T2DM a yearly 2.3% increase across all ages. Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase). A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity.

Alzheimer’s disease (AD) onset and progression is influenced by a complex interplay of several environmental and genetic factors, one of them gender. Pronounced gender differences have been observed both in the relative risk of developing AD and in clinical disease manifestations. A molecular level understanding of these gender disparities is still missing, but could provide important clues on cellular mechanisms modulating the disease and reveal new targets for gender-oriented disease-modifying precision therapies. We therefore present here a comprehensive single-cell analysis of disease-associated molecular gender differences in transcriptomics data from the neocortex, one of the brain regions most susceptible to AD, in one of the most widely used AD mouse models, the Tg2576 model. Cortical areas are also most commonly used in studies of post-mortem AD brains. To identify disease-linked molecular processes that occur before the onset of detectable neuropathology, we focused our analyses on an age with no detectable plaques and microgliosis. Cell-type specific alterations were investigated at the level of individual genes, pathways, and gene regulatory networks. The number of differentially expressed genes (DEGs) was not large enough to build context-specific gene regulatory networks for each individual cell type, and thus, we focused on the study of cell types with dominant changes and included analyses of changes across the combination of cell types. We observed significant disease-associated gender differences in cellular processes related to synapse organization and reactive oxygen species metabolism, and identified a limited set of transcription factors, including Egr1 and Klf6 , a s key regulators of many of the disease-associated and gender-dependent gene expression changes in the model. Overall, our analyses revealed significant cell-type specific gene expression changes in individual genes, pathways and sub-networks, including gender-specific and gender-dimorphic changes in both upstream transcription factors and their downstream targets, in the Tg2576 AD model before the onset of overt disease. This opens a window into molecular events that could determine gender-susceptibility to AD, and uncovers tractable target candidates for potential gender-specific precision medicine for AD.