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Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepsin is a serine protease whose deregulation leads to tumor invasion and metastasis in many tumor types. In colorectal cancer, the role of hepsin is unknown, so we aimed to study the correlations between its expression and clinical-histopathological variables of patients with this cancer. We recruited 169 patients with localized disease and 118 with metastatic cancer at diagnosis, and then, we measured hepsin staining from primary biopsy in order to correlate it with time-to-event variables, laboratory data, genetic alterations, histologic features, etc. Our results demonstrated hepsin was an independent prognosis factor for metastasis and thrombosis in patients with localized disease, whereas among metastatic subjects, lower levels of hepsin were associated with highest tumor dedifferentiation and spread to distant organs. These results point to hepsin as a potential biomarker for considerable complications in patients with colorectal cancer. In addition, this article brings to light new information about the implication of hepsin in colorectal cancer. Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal–Wallis tests, Kaplan–Meier and Aalen–Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, our primary aim was to evaluate LMO2 mRNA expression in tissue, an area with limited research. Studies assessing LMO2 mRNA expression overlook tissue morphology since they have relied on microarray platforms or PCR methods. Our results show a reliable method to identify LMO2 mRNA expression in tissues, capturing the reported biologic features of LMO2, that may be useful to study LMO2 mRNA expression in hematological neoplasms and solid tumors. Background: LMO2 is a relevant gene involved in B-cell ontogeny and a survival predictor of aggressive large B-cell lymphomas (aLBCL). Most studies assessing LMO2 mRNA expression have relied on microarray platforms or qRT-PCR methods, overlooking tissue morphology. In this study, we evaluate LMO2 RNA expression by chromogenic in situ hybridization (CISH) in normal tissue and in a series of 82 aLBCL. Methods: LMO2 CISH was performed in formalin-fixed paraffin-embedded tissues, scored by three different methods, and correlated with a transcriptome panel. Results: We obtained statistically significant results correlating the methods of evaluation with LMO2 protein expression and gene expression results. Normal tonsil tissue showed high levels of LMO2, particularly within the light zone of the germinal center. Conversely, in aLBCL, a notable reduction in LMO2 expression was noted, remarkably in cases carrying MYC rearrangements. Furthermore, significant results were obtained through overall survival and Cox regression survival analysis, incorporating International Prognostic Index data alongside LMO2 expression levels. Conclusions: We show a reliable method to identify LMO2 mRNA expression by CISH, effectively capturing many of the reported biologic features of LMO2. [ABSTRACT FROM AUTHOR]

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55–70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Taxes on the consumption of certain products have played a key role in public revenue analysis in European countries. This work assesses the differences in tax planning for new non-combustion products across some European territories. Through theoretical analysis, the paper has three distinct aspects. Firstly, we show the taxpayer profile in different countries. Secondly, the study analyzes the risks for the health system and the individual. Thirdly, the design of the national tobacco tax is based on previous experience and planning in Europe. This paper concludes with a case study for different countries: (1) Spain "vapers" and "smokers", where the analysis is based on micro-data from the European Health Interview Survey 2020. (2) Sweden, with the analysis of snus, shows it as a practice on how to reach economic savings while decreasing economic costs thanks to the nudging of consumers towards better products. The results show taxation and, especially, land taxation should consider differences in planning in the case of new products, such as non-combustion products, given the user per capita income and the potential lower health risks involved. [ABSTRACT FROM AUTHOR]

Over the last few decades, within the framework of remarkable urban expansion accompanying a real-estate boom in Spain, it has been medium-sized cities that have registered the most drastic changes in morphology. Currently, about 50% of urbanised land was developed after 1980. Historically compact and dense urban structures have been transformed, with new urbanised spaces expanding into the outskirts. High land consumption has created sprawling, fragmented and scattered urban areas. These are new, more complex and multifunctional urban structures, and there has been a change in the scale of urbanisation, in the forms and in the resulting urban landscape. However, the growth model which has caused these transformations is defined by hardly sustainable land-use patterns. The number of medium-sized cities has increased by around 50%, while the number of houses built has grown by 109% and developed land by 87% between 1981 and 2021. This paper analyses these recent dynamics through the statistical treatment of growth patterns and their cartographic analysis using GIS technology. The significant modification of urban forms at this scale in the Spanish urban system is confirmed. The paper also reflects on the lack of sustainability in the prevailing model with respect to the 2030 city strategy. [ABSTRACT FROM AUTHOR]

Biological therapies (BTs) indicated for psoriasis are highly effective; however, not all patients obtain good results, and loss of effectiveness is the main reason for switching. Genetic factors may be involved. The objective of this study was to evaluate the influence of single-nucleotide polymorphisms (SNPs) on the drug survival of tumor necrosis factor inhibitors (anti-TNF) medications and ustekinumab (UTK) in patients diagnosed with moderate-to-severe psoriasis. We conducted an ambispective observational cohort study that included 379 lines of treatment with anti-TNF (n = 247) and UTK (132) in 206 white patients from southern Spain and Italy. The genotyping of the 29 functional SNPs was carried out using real-time polymerase chain reaction (PCR) with TaqMan probes. Drug survival was evaluated with Cox regression and Kaplan–Meier curves. The multivariate analysis showed that the HLA-C rs12191877-T (hazard ratio [HR] = 0.560; 95% CI = 0.40–0.78; p = 0.0006) and TNF-1031 (rs1799964-C) (HR = 0.707; 95% CI = 0.50–0.99; p = 0.048) polymorphisms are associated with anti-TNF drug survival, while TLR5 rs5744174-G (HR = 0.589; 95% CI = 0.37–0.92; p = 0.02), CD84 rs6427528-GG (HR = 0.557; 95% CI = 0.35–0.88; p = 0.013) and PDE3A rs11045392-T together with SLCO1C1 rs3794271-T (HR = 0.508; 95% CI = 0.32–0.79; p = 0.002) are related to UTK survival. The limitations are the sample size and the clustering of anti-TNF drugs; we used a homogeneous cohort of patients from 2 hospitals only. In conclusion, SNPs in the HLA-C, TNF, TLR5, CD84, PDE3A, and SLCO1C1 genes may be useful as biomarkers of drug survival of BTs indicated for psoriasis, making it possible to implement personalized medicine that will reduce financial healthcare costs, facilitate medical decision-making and improve patient quality of life. However, further pharmacogenetic studies need to be conducted to confirm these associations. [ABSTRACT FROM AUTHOR]

The deregulation of the electricity markets in the European Union and the transformation caused by digital technologies and customer-centric strategies have altered the industry ecosystem, forcing companies to adapt to the new scenario. This research study aims to give a global overview of the digital transformation and channel integration of free-market electricity retailers in Spain from a consumer's perspective. The analysis includes all free-market electricity retailers that operate at the national scale, explores the level of digital transformation and channel integration of these companies based on a structured set of indicators, and measures them using the mystery shopper technique. The results show important differences between leading retailers and the rest of companies, evidence an important lag of the sector when compared to other retail markets and an overall lack of multichannel and omnichannel strategies, show a strong effort of retailers in online billing and self-service customer data management, and reveal shortcomings in the availability of communication channels with customers. [ABSTRACT FROM AUTHOR]

The regulation of the electricity sector, in general and in the particular case of Spain, has been brilliantly analysed by economists and contemporary jurists placing the emphasis, preferably, on economic efficiency and social justice. This article, based on the writings of economic historians in recent years, has as its objective to shed light on the logic to regulatory changes in Spain. Exactly as has been done for other countries, the explanation of factors and of the characteristics of this regulatory change, without doubt, will contribute to the understanding of its special nature within the overall international panorama, as well as a better understanding of the contributions of other previous and future works from different perspectives of analysis. The conclusions on the historical construction of the regulation of the electricity industry until the twentieth century allow us to define four big stages, deeply conditioned by their political regimes and the economic circumstances of the country, as well as by the unequal importance of economic agents in the taking of decisions: powerful energy companies, weak governments, and a complete lack of consumer input. [ABSTRACT FROM AUTHOR]

Multitarget anti-Alzheimer agents are the focus of very intensive research. Through a comprehensive bibliometric analysis of the publications in the period 1990–2020, we have identified trends and potential gaps that might guide future directions. We found that: (i) the number of publications boomed by 2011 and continued ascending in 2020; (ii) the linked-pharmacophore strategy was preferred over design approaches based on fusing or merging pharmacophores or privileged structures; (iii) a significant number of in vivo studies, mainly using the scopolamine-induced amnesia mouse model, have been performed, especially since 2017; (iv) China, Italy and Spain are the countries with the largest total number of publications on this topic, whereas Portugal, Spain and Italy are the countries in whose scientific communities this topic has generated greatest interest; (v) acetylcholinesterase, β-amyloid aggregation, oxidative stress, butyrylcholinesterase, and biometal chelation and the binary combinations thereof have been the most commonly pursued, while combinations based on other key targets, such as tau aggregation, glycogen synthase kinase-3β, NMDA receptors, and more than 70 other targets have been only marginally considered. These results might allow us to spot new design opportunities based on innovative target combinations to expand and diversify the repertoire of multitarget drug candidates and increase the likelihood of finding effective therapies for this devastating disease. [ABSTRACT FROM AUTHOR]

In recent years, courier and home delivery services have experienced extensive growth around the world. These platform companies, that operate through applications on smartphones, have experienced the benefits of the technological leap that has been produced by the conditions imposed by the COVID-19 pandemic and its restrictions on traditional commerce. This business model integrates novel elements that move away from a classic contractual relationship, employer-employee. They combine a strong cooperative culture, integrated by company values and principles that make the rider assume an identity that defines him/her as a worker and a member of a community. In addition, on the other hand, precarious working conditions, in which extreme competitiveness among colleagues and dependence on high standards of service compliance are encouraged. In Spain, there is a lack of research on the identity of workers in this type of platform. By means of in-depth interviews with drivers of two different companies in the Region of Murcia (Spain), the main objective of this article is to identify and describe the figure of what we define as homo rider, understood as a prototype individual in the context of contemporary labor relations, linked to the incorporation of new technologies for the intermediation and interconnection between people, goods and services. We approach to the socioeconomic spectrum and identity imaginary of the homo rider through two dimensions, material and ideological, to construct this broad, ambiguous figure between self-employment and wage-earner that would also represent a complex relation between precarious work and new technologies. [ABSTRACT FROM AUTHOR]

Solar energy is in high demand due to its environmental benefits and economic potential; however, concerns remain about the total impact it holds. In 2020, for Spain, Castilla-La Mancha was the second autonomous community with the highest photovoltaic energy production. Thus, a systematic review on 15 large-scale PV solar energy projects was carried out to assess the industry impacts, through environmental impact assessment (EIA), within the Autonomous Community of Castilla—La Mancha. An estimation of these impacts from a pre-operational approach is presented, based on primary energy needs and emissions discarded during its life cycle due to the manufacture, operation, and recycling of the photovoltaic modules. Based on both the life cycle assessment (LCA) and EIA, the approaches were compared with the results obtained. The obtained results suggest that determining the actual impacts of power plants in this region could provide justified information for the public administration and technicians in the measures for the installation and operation of PV plants and the future benefits of renewable solar technologies. Furthermore, the results indicate the possibility to recognize the relationship between the size of the plant and a high generation capacity, with a shorter time to pay for emissions from the manufacture and recycling of panels, suggesting that it is around 1.66–2.08 years for the Castilla-La Mancha region. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) might be negatively associated with thwarted belongingness and perceived burdensomeness. To date, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of lifetime NSSI in Spanish adolescents. Aims: (a) To test whether thwarted belongingness and perceived burdensomeness are associated with frequency of lifetime NSSI; (b) to test whether MIL moderates the association between thwarted belongingness and frequency of lifetime NSSI; and (c) to test whether MIL moderates the association between perceived burdensomeness and frequency of lifetime NSSI. Method: The sample consisted of N = 1531 participants (n = 736, 48.1%, were men, and n = 795, 51.9%, were women) between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescent Version, and Interpersonal Needs Questionnaire. Moderation analyses were performed. Results: No statistically significant differences were found in the frequency of lifetime NSSI in the adolescents based on gender. Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of lifetime NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of lifetime NSSI, and between perceived burdensomeness and the frequency of lifetime NSSI. Conclusions: Thwarted belongingness and perceived burdensomeness might be positively associated with the frequency of lifetime NSSI, and MIL might be negatively associated with the frequency of lifetime NSSI. Thus, adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve assessment and treatment protocols for adolescents with NSSI. [ABSTRACT FROM AUTHOR]

Over the last few decades, public programs have driven the gradual adoption of information and communication technologies (ICTs) in education. The most ambitious project in Spain so far was Escuela 2.0, which provided students from the regions that opted into the program with laptops. The objective of this paper is to evaluate the impact of this program on school performance and productivity. To do this, we developed a new methodological approach based on combining causal inference techniques and the analysis of production frontiers. We calculated the differences in productivity and performance between treated and control schools using the base-group Camanho–Dyson Malmquist index and the base-group performance gap index. We estimate the impact of the program as the variation of these differences, following the essence of the difference-in-differences analysis. The main results are that Escuela 2.0 had a negative impact on performance and productivity. [ABSTRACT FROM AUTHOR]

Simple Summary: In temperate zones of the Earth, some mammalian species reproduce seasonally whereas others do it continuously. Other species are summer breeders in the north and winter breeders in the south. Thus, the reproductive pattern seems not to be a species-specific but a population-specific trait. We investigated the reproduction pattern of the Mediterranean pine vole, Microtus duodecimcostatus, in the area around the city of Granada in Southern Spain, and found that individuals living in wastelands reproduce seasonally whereas those living in close poplar plantations (just 8 km apart) reproduce throughout the year, as did voles captured in wastelands and kept in captivity. These animals represent thus a paradigm of an opportunistic breeder as particular individuals stop breeding or not, depending on the environmental conditions they face at any moment. Sexually inactive male voles undergo complete testis inactivation and their sperm production is halted. The immune system in active testes is depressed, a phenomenon known as "immune privilege" that protect germ cells from autoimmune attack. We studied gene activity in active and inactive testes and our results indicate that such an immune privilege is lost in inactive testes, suggesting an important role for this process during testis regression. Most mammalian species of the temperate zones of the Earth reproduce seasonally, existing a non-breeding period in which the gonads of both sexes undergo functional regression. It is widely accepted that photoperiod is the principal environmental cue controlling these seasonal changes, although several exceptions have been described in other mammalian species in which breeding depends on cues such as food or water availability. We studied the circannual reproductive cycle in males of the Mediterranean pine vole, Microtus duodecimcostatus, in the Southeastern Iberian Peninsula. Morphological, hormonal, functional, molecular and transcriptomic analyses were performed. As reported for populations of other species from the same geographic area, male voles captured in wastelands underwent seasonal testis regression in summer whereas, surprisingly, those living either in close poplar plantations or in our animal house reproduced throughout the year, showing that it is the microenvironment of a particular vole subpopulation what determines its reproductive status and that these animals are pure opportunistic, photoperiod-independent breeders. In addition, we show that several molecular pathways, including MAPK, are deregulated and that the testicular "immune privilege" is lost in the inactive testes, providing novel mechanisms linking seasonal testosterone reduction and testis regression. [ABSTRACT FROM AUTHOR]

The recent growth of cooperative housing in Spain questions existing design standards and regulations as well as cultural norms of ownership, management and current housing typologies. This paper analyzes the design opportunities and challenges emerging from this. It studies the transformative capacity of housing cooperatives and how the realization of new social, spatial and economic demands is restricted by regulatory and administrative frameworks that limit collective ownership and use. Based on a case study analysis of recent projects in Barcelona, the paper discusses how regulations condition housing design, but also why changing ideas of ownership, household and dwelling structures require a review of how regulations are formulated and implemented. It examines this in the context of designing with housing cooperatives and their ethos defined by engagement in and responsibility for all decision-making processes and self-management. In cooperative housing, architecture is a process, not a product, one that extends beyond the completion of a building. This gives credibility to the claim of cooperative housing not just as a grassroots response to housing failures, but also as a political project of democratization and social transformation. [ABSTRACT FROM AUTHOR]

On the path towards the decarbonization of the electricity supply, flexibility and demand response have become key factors to enhance the integration of distributed energy resources, shifting the consumption from peak hours to off-peak hours, optimizing the grid usage and maximizing the share of renewables. Despite the technical viability of flexible services, the reduction of greenhouse gas emissions has not been proven. Traditionally, emissions are calculated on a yearly average timescale, not providing any information about peak hours' environmental impact. Furthermore, peak-hours' environmental impacts are not always greater than on the base load, depending on the resources used for those time periods. This paper formulates a general methodology to assess the potential environmental impact of peak-hourly generation profiles, through attributional life cycle assessment. This methodology was applied to five different countries under the INVADE H2020 Project. Evaluation results demonstrate that countries like Spain and Bulgaria could benefit from implementing demand response activities considering environmental aspects, enhancing potential greenhouse gas reductions by up to 21% in peak hours. [ABSTRACT FROM AUTHOR]

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.