Complutense University of Madrid
Recent publications
Cancer immunotherapy strategies based on the endogenous secretion of T cell-redirecting bispecific antibodies by engineered T lymphocytes (STAb-T) are emerging as alternative or complementary approaches to those based on chimeric antigen receptors (CAR-T). The antitumor efficacy of bispecific anti-CD19 × anti-CD3 (CD19×CD3) T cell engager (BiTE)-secreting STAb-T cells has been demonstrated in several mouse models of B-cell acute leukemia. Here, we have investigated the spatial topology and downstream signaling of the artificial immunological synapses (IS) that are formed by CAR-T or STAb-T cells. Upon interaction with CD19-positive target cells, STAb-T cells form IS with structure and signal transduction, which more closely resemble those of physiological cognate IS, compared to IS formed by CAR-T cells expressing a second-generation CAR bearing the same CD19-single-chain variable fragment. Importantly, while CD3 is maintained at detectable levels on the surface of STAb-T cells, indicating sustained activation mediated by the secreted BiTE, the anti-CD19 CAR was rapidly downmodulated, which correlated with a more transient downstream signaling. Furthermore, CAR-T cells, but not STAb-T cells, provoke an acute loss of CD19 in target cells. Such differences might represent advantages of the STAb-T strategy over the CAR-T approach and should be carefully considered in order to develop more effective and safer treatments for hematological malignancies.
Background The “Primary Immunodeficiencies (PIDs) principles of care” were published in 2014 as the gold standard for care of patients with PIDs, setting a common goal for stakeholders to ensure that patients with PID have access to appropriate care and good quality of life. Since then, IPOPI (the International Patient Organisation for Primary Immunodeficiencies), has been working with national PID patient organisations as well as collaborating with scientific and medical institutions and experts to bring these principles closer to the day-to-day life of individuals with PIDs. Method The six PID Principles of Care were revised to consider advances in the field, as well as political developments that had occurred after their initial publication in 2014. Based on this revision the list was updated, and a new principle was added. The six established principles were: diagnosis, treatment, universal health coverage, specialised centres, national patient organisations and registries. Each principle was structured and measured through a series of criteria, and was given the same weight, as they have been considered to all be equally important. Specific weights were attributed to the criteria depending on their relevance and importance to quantify the principle. The index was translated into a survey for data collection: initially involving data from selected countries for a pilot, followed by integration of data from IPOPI’s national member organisations and key countries. Results The PID Life Index was developed in 2020 to assess the status of the PID environment and the implementation of the 6 principles worldwide. The Index allows for benchmarking countries either according to a set of principles and criteria or based on the user’s preferences. This can be displayed in an interactive map or through a data visualisation system. Conclusion The PID Life Index has been developed successfully and has potential to become an important source of information for PID stakeholders, to increase awareness and information as well as support advocacy initiatives on PIDs nationally, regionally or globally.
Since the emergence of Bitcoin, cryptocurrencies have grown significantly, not only in terms of capitalization but also in number. Consequently, the cryptocurrency market can be a conducive arena for investors, as it offers many opportunities. However, it is difficult to understand. This study aims to describe, summarize, and segment the main trends of the entire cryptocurrency market in 2018, using data analysis tools. Accordingly, we propose a new clustering-based methodology that provides complementary views of the financial behavior of cryptocurrencies, and one that looks for associations between the clustering results, and other factors that are not involved in clustering. Particularly, the methodology involves applying three different partitional clustering algorithms, where each of them use a different representation for cryptocurrencies, namely, yearly mean, and standard deviation of the returns, distribution of returns that have not been applied to financial markets previously, and the time series of returns. Because each representation provides a different outlook of the market, we also examine the integration of the three clustering results, to obtain a fine-grained analysis of the main trends of the market. In conclusion, we analyze the association of the clustering results with other descriptive features of cryptocurrencies, including the age, technological attributes, and financial ratios derived from them. This will help to enhance the profiling of the clusters with additional descriptive insights, and to find associations with other variables. Consequently, this study describes the whole market based on graphical information, and a scalable methodology that can be reproduced by investors who want to understand the main trends in the market quickly, and those that look for cryptocurrencies with different financial performance.In our analysis of the 2018 and 2019 for extended period, we found that the market can be typically segmented in few clusters (five or less), and even considering the intersections, the 6 more populations account for 75% of the market. Regarding the associations between the clusters and descriptive features, we find associations between some clusters with volume, market capitalization, and some financial ratios, which could be explored in future research.
Fire is a natural agent with a paramount role in ecosystem functioning and biodiversity maintenance. Still, it can also act as a negative force against many ecosystems. Despite some knowledge of the interactions of fire and vegetation, there is no clear understanding of how different components of fire regimes (i.e., severity, history, or frequency) influence known patterns of animal communities. Therefore, we performed a systematic review on the global responses of arthropods, birds, mammals, reptiles, and amphibians to different fire regimes. Specifically, we focused on assessing how fire severity, history, and frequency modulate the effect of fire on the richness and abundance of faunal communities. We conducted a systematic review of 566 papers retrieved from the Scopus database. We also scrutinized all the documents included in the meta-analysis of Pastro et al. (Pastro et al. Glob Ecol Biogeogr 23:1146–1156, 2014). Our selection criteria excluded studies without data on species richness or abundance. We also excluded studies without adequate controls and those without information about the fire regime of the study zone. After careful examination, we used data from 162 studies to perform a quantitative meta-analysis. From the 162 studies meeting our selection criteria, nearly 60% of the studies are from North America, 25% from Australia, 11% from Europe, and 4% from the tropics. According to the ecological role of fire, 90% of the studies were carried out in fire-dependent ecosystems (i.e., conifer forests, natural savannas, pastures). Finally, 40% of the studies analyzed birds, 22% mammals, and 20% arthropods. The meta-analysis of the available evidence indicates that fire history is an important modulator of animal richness and abundance. Whether negative or positive, animal responses depended on the time since the last fire event. Considering that short-term studies may not capture such a long-term effect on fauna, this translates to more challenges at implementing fire management strategies. Whether or not we can anticipate the impact of the fire will then depend on future efforts to implement long-term research.
First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT ( d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.
Abstract Background Resistance to colistin was an uncommon phenomenon traditionally linked to chromosome point mutations, but since the first description of a plasmid-mediated colistin-resistance in late 2015, transmissible resistance to colistin has become a Public Health concern. Despite colistin is considered as a human last resort antibiotic, it has been commonly used in swine industry to treat post-weaning diarrhoea in piglets. However, the progressively increase of colistin resistance during the last decade led to the Spanish Medicines and Healthcare Products Agency (AEMPS) to launch a strategic and voluntary plan aimed to reduce colistin consumption in pig production. Our longitudinal study (1998–2021) aimed to evaluate the trend of colistin resistance mediated through the mcr-1 mobile gene in Spanish food-producing pig population and compare it with published polymyxin sales data in veterinary medicine to assess their possible relationships. Results The first mcr-1 positive sample was observed in 2004, as all samples from 1998 and 2002 were mcr-1 PCR-negative. We observed a progressive increase of positive samples from 2004 to 2015, when mcr-1 detection reached its maximum peak (33/50; 66%). From 2017 (27/50; 54%) to 2021 (14/81; 17%) the trend became downward, reaching percentages significantly lower than the 2015 peak (p
Objective To interpret the current evidence on the prevalence of neurodevelopmental disorders (NDDs) through a systematic review based on both DSM-5 (2013) and PRISMA criteria. Method Empirical studies complying with the PRISMA guidelines were identified from four databases (PubMed, Scopus, Science Direct, and ProQuest) and systematically reviewed. In total, 17 articles were selected for the study. Results In the scientific literature, there have been only a few studies measuring the prevalence of NDDs according to the DSM-5 (2013) criteria in people under 18 years old. The reported prevalence rates were as follows: intellectual disability (ID), 0.63%; attention-deficit/hyperactivity disorder (ADHD), 5–11%; autism spectrum disorder (ASD), 0.70–3%; specific learning disorder (SLD), 3–10%; communication disorders (CDs), 1–3.42%; and motor disorders (MDs), 0.76–17%. Although there is extensive literature on specific disorders, NDDs have rarely been assessed as a whole. All of the reviewed studies support the idea that such disorders can be considered chronic, heterogeneous, underdiagnosed conditions and that comorbidity of multiple NDDs is the norm. Likewise, it is estimated that the prevalence of the most studied disorders, such as ADHD, ASD and SLD, remains stable over time and is consistent in different cultures, ages, ethnicities and sexes. Conclusion The studies reviewed lead us to conclude that the prevalence rate of NDDs fluctuates globally between 4.70 and 88.50%; these variations depend on methodological aspects such as estimation procedures, as well as on sociocontextual phenomena. It is also important to consider that the prevalence found is probably highly influenced by the activity of the countries in the diagnosis and training of professionals who care for children and adolescents. Hence, there is a need for a secondary intervention in the fields of public health and education to minimize socioemotional consequences, prevent academic failure, and reduce the economic cost to society.
Background: Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40% to 59% of these patients worldwide. The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light (IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments. To our knowledge, this is the first series analyzing the therapeutic effect of this treatment option in this type of patients. Methods: This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology. All patients received four sessions of IPL treatment using the Optima IPL system (Lumenis, Yokneam, Israel) adjusted to the official optimized Lumenis setting. Changes in symptomatology, corneal staining, conjunctival hyperemia, non-invasive break-up time (NIBUT), tear osmolarity, tear meniscus height (TMH), meiboscore and meibomian gland expressibility was analyzed after treatment. Results: Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires [ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED) and symptom assessment questionnaire in dry eye (SANDE)] as well as with the visual analogue scale (P < 0.001). Mean change in OSDI was - 15.0 ± 11.3. A significant reduction was found after treatment in the corneal staining score (P < 0.001). A significant reduction was found in tear film meniscus height (P = 0.012), as well as in tear film osmolarity (P = 0.001). A significant reduction was also found in meibomian gland expressibility (P = 0.003), changing the percentage of grade 3 eyes from 44.4% before IPL to 17.2% after treatment. Conclusions: IPL therapy combined with meibomian gland expression (MGX) seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments, with an additional improvement in clinical signs, such as tear osmolarity and corneal staining.
Background Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA. Methods Cholangiocarcinogenesis was induced in rats (TAA) and mice ( Jnk Δhepa + CCl 4 + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRAS G12D cells. Cell signaling, growth, gene regulation and [U- ¹³ C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model. Results Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRAS G12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRAS G12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRAS G12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression. Conclusions In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA.
Species richness is a widely used proxy for patterns of biodiversity variation in metacommunities. However, deeper analyses require additional metrics, such as the occupancy-frequency distributions (SOFD) of different local communities. The SOFD patterns indicate the number of shared species between study sites; therefore, they can provide new insights into the current debate on how to create more biodiversity-friendly cities. Breeding birds were counted from 593 point-count stations located in five 500 m × 500 m squares in land-sharing (LSH; low-density built areas interspersed with green spaces) and five similar nearby squares in land-sparing (LSP; densely built-up with set-aside, large-sized, continuous green spaces) landscapes in nine cities across Europe. High beta-diversity (with over 42% of the 103 species detected being restricted to a single city and only 7% found in all studied cities) showed the uniqueness of cities at the continental scale. Urban bird metacommunities followed the unimodal-satellite SOFD pattern at the European continental scale but a bimodal symmetric or asymmetric distribution at the city-level scale, suggesting that many common species occur in cities on a smaller scale. The LSP urban areas followed a unimodal satellite SOFD pattern with numerous rare species. In contrast, the LSH areas fit several types of bimodal SOFD patterns equally well, where communities share several common species. The findings also highlight the need to use multi-scale approaches to analyze the effects of LSH-LSP urban designs on urban bird diversity.
A Sector-based Fresnel zone plate consists of a binary diffractive lens composed of a mosaic of sectors of Fresnel zone plates with different focal distances. When these focal distances are linearly distributed within the sectors, dual focus is obtained. Besides, we explore the possibility to generate an extended depth-of-focus lens by using a cubic distribution of the focal distances assigned to the sectors and optimizing the weight factors given to the terms of the cubic polynomial. Finally, numerical simulations based on the Rayleigh-Sommerfeld approach are carried out and experimental verifications by using a Spatial Light Modulator are performed, showing high agreement. The proposed kind of zone plate has potential applications in different research fields such as microscopy, lithography, data storage, or imaging.
Forest expansion can make an important contribution to the 2015 Paris Agreement, through offsetting Greenhouse gas (GHG) emissions. EU, UK and Scottish forest policy encourages substantial forest expansion. Unfortunately, policy is still inadequately informed by high resolution data, and often assumes a fairly homogenous landscape, uniformly suitable soil types and idealised ‘average’ tree timber yields, while carbon emissions caused by soil disturbance during planting, and changes in climate are rarely adequately considered. Also, the proportional contribution of afforestation targets to national mitigation needs is often overlooked which could lead to over-reliance on tree planting. We address these shortcomings through an integrated modelling approach which estimates net carbon gain for eleven tree species accounting for the interactions between climate, soil and planting practices. We present detailed spatial results for a case study area (Scotland), showing where forest expansion would be likely to result in overall carbon gains, accounting for the differentiated spatial variability of timber yield classes for each one of the species considered including present and future climate. The results showed that upland ecosystems, whose soils are rich in carbon, were vulnerable to net carbon loss, particularly with intensive ground preparation and planting practices. While the prevalence of mineral soils in the lowlands makes them a safer option for planting in theory, these are also areas which might conflict with agricultural activities. Our findings strongly support the notion that both “the right tree in the right place” and “no trees in the wrong place” are important messages for practitioners. In terms of the total UK and Scottish carbon footprints, the magnitude of the offset obtained in 30 years if afforestation goals were fully reached would likely be around 1% of the UK total business as usual GHG footprint and around 10% of the Scottish footprint. Our results can help to improve the targeting of incentives and investments in forest and woodland expansion, but also reinforce the need to pursue emissions reductions in a variety of ways throughout all sectors.
CoFe layered double oxide (CoFe LDO) anchored on g-C3N4 was prepared by mixing appropriate amounts of CoFe layer double hydroxide and melamine at moderate synthesis temperatures. The resulting CoFe LDO/g-C3N4 composite has superior properties in peroxymonosulfate (PMS) activation, resulting in remarkable activity in catalyzing paracetamol degradation. It has been able to degrade 10 mg/L paracetamol in less than 10 min in darkness by using 0.2 g/L catalyst and 0.5 mM PMS dosages. The effects of PMS and catalyst dosage, initial pH and coexisting anions were also investigated. Negligible cation leaching, enhanced reusability and enhanced stability make CoFe LDO/g-C3N4 an attractive compound for environmental pollution abatement. The influence of g-C3N4 on lowering Co and Fe valence states in CoFe LDO compounds by covalent stimulates the oxidant radical (SO4⁻ and OH) production and concomitantly paracetamol degradation. Electro magnetic resonance experiments and a so-called chemical probe were used to identify SO4⁻ as the dominant radical in the degradation processes. Interestingly, X-ray absorption spectroscopy and electrochemical measurements revealed the existence of a second contributing mechanism, based on a pure electron transfer process from the pollutant to PMS mediated by the catalyzer. These findings, pioneer a new method for the mechanism of coupling radical and electron transfer processes that act synergistically to promote paracetamol degradation in scarcely 10 min in darkness.
The catalytic properties of phosphate rocks (natural phosphates: NP) and their role as a catalyst or catalyst support were discussed in the light of the versatility and potential of phosphate‐based catalysts. NP have both acidic and/or basic properties, structure flexibility, capacity to disperse a catalytic active phase (e.g. metal salts), and low cost. Thus, NP have been studied as catalytic materials in several chemical processes, in particular in organic synthesis, with interesting catalytic efficiency. This chapter is dedicated to the study of NP in several application in organic chemistry such as condensation, cross‐coupling, alkylation reactions, hydration of aromatic nitriles, hydrogenation, reduction, reforming of methane, etc.
Radar data from the Mars Express spacecraft show bright subsurface reflections in the Planum Australe area that could be due to liquid water located at a depth of 1.5 km (Orosei et al., 2018). If this interpretation of the data is correct, the presence of such water would have important implications for the present-day thermal state of the region. In this article, we recalculate the depth of the liquid water and we analyze the influence of the regional thermal properties in the surface heat flow and the subsurface temperatures. We have obtained a new depth to the bright reflector between 1.3 and 1.5 km by using a temperature dependent relative permittivity for the water ice and taking into account the dust content in the area. We show that regional properties in the SPLD moderately influence the thermal state of the area where the liquid water is located. A better knowledge of the porosity profile in the studied area is necessary to constrain surface heat flow and subsurface temperatures accurately. Our findings are in agreement with previous work that shows anomalously high local heat flows would be required to sustain liquid water at this location.
Background The goal of this study was to analyze psychometric properties of the Spanish PROMIS Pediatric Pain Interference short form (PROMIS-PPI) in a sample of Spanish children and adolescents. Methods In a hospital pediatric sample it was studied the structure scale (exploratory and confirmatory analysis), construct validity, convergent validity, and reliability (internal consistency). Findings 163 children and adolescents (mean age 13.3 years; SD 2.01; 39.26% female) with and without chronic pain completed measures pertaining to their pain experience. Psychometric analysis showed the PROMIS-PPI Spanish version maintains the original one-factor model of the scale, excellent internal consistency (Cronbach's α coefficient 0.90 (95% CI 0.88–0.92)), and convergent validity (showed a positive, significant, and moderate magnitude correlation [r from 0.330 to 0.604] with pediatric quality of life, child and parent pain intensity, and showed a low correlation with the number of medical consultations in the last year). Discussion The Spanish PROMIS-PPI scale is a valid and reliable tool. It is recommended for research and clinical care in pediatric populations. Application to practice The results provide evidence that the Spanish version of PROMIS-PPI is valid and reliable tool. Health professionals who work with children in risk to develop persistent pain, will have access to short tool with highest evidence, for assess pain interference.
Determining the influence of climate in driving the global distribution of soil microbial communities is fundamental to help predict potential shifts in soil food webs and ecosystem functioning under global change scenarios. Herein, we used a global survey including 80 dryland ecosystems from six continents, and found that the relative abundance of ecological clusters formed by taxa involved in bacteria-fungi and bacteria-cercozoa bipartite networks was highly sensitive to changes in temperature and aridity. Importantly, such a result was maintained when controlling for soil, geographical location and vegetation attributes, being pH and soil organic carbon important determinants of the relative abundance of the ecological clusters. We also identified potential global associations between important soil microbial taxa, which can be useful to support the conservation of terrestrial ecosystems under global change scenarios. Our results suggest that increases in temperature and aridity such as those forecasted for the next decades in drylands could potentially lead to drastic changes in the community composition of functionally important bipartite networks within soil food webs. This could have important but unknown implications for the provision of key ecosystem functions and associated services driven by the organisms forming these networks if other taxa cannot cope with them. This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
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22,561 members
Juan MR Parrondo
  • Departamento de Estructura de la Materia Física Térmica y Electrónica
Celia Diaz Catalan
  • Department of Sociology: Methods and Theory
Joaquin Lopez Herraiz
  • Nuclear Physics Group
Francisco Ortega
  • Fac. of Chemistry / Department of Physical Chemistry I
Carlos Guillen
  • Department of Biochemistry and Molecular Biology
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