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Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivoin an atherosclerotic mouse model (ApoE–/–mice on a high-fat diet). This study demonstrates the potential of engineering protein–nanoparticle hybrids as versatile platforms for developing targeted in vivoMRI contrast agents.

The main pillar in the advancement of chemical looping (CL) technology is the development of oxygen carriers that are reactive and mechanically resistant without neglecting their cost and environmental impact. In this work, the applicability of a waste with a high iron oxide content in different processes based on the chemical looping (CL) concept is analyzed. Experiments were performed in a TGA apparatus under conditions that would be present in different CL processes: chemical looping combustion (CLC), chemical looping reforming or gasification (CLR or CLG), and chemical looping water or CO2splitting (CLWS or CO2SPLIT). The oxygen carrier performed well even under highly reduced conditions and maintained its reactivity. Independently of the redox transformation considered, it was observed that iron migration to the surface of FS_GR particles took place. The high rate index with methane found in the transformation Fe2O3/Fe3O4made this material promising for CLC. FS_GR material also met the reactivity requirements set for the CO2SPLIT process. Thus, it will be further considered as a potential oxygen carrier for diverse CL applications.

This article develops model-based predictors for area-level proportions of employed men and women by occupation sectors and for entropies and divergence indexes (DIs) within and between sex groups. Since the direct estimators of the proportions add up to one in the occupational sections, they are compositions that can be imprecise if the sample sizes are small. We fit a multivariate Fay–Herriot model to logratio transformations of the direct estimators of the proportions. Small area estimators of the proportions, entropies, and DIs are derived from the fitted model and the corresponding mean squared errors are estimated by parametric bootstrap. Several simulation experiments designed to analyze the behavior of the introduced model-based predictors are carried out. We give an application to Spanish Labour Force Survey data from 2022. The target is to investigate the state of sex occupational entropies and divergences in Spanish provinces.

BL Lac objects are a class of jetted active galactic nuclei that do not exhibit or have weak emission lines in their optical spectra. Recently, the first γ-ray emitting BL Lac beyond z=3, 4FGL J1219.0 +3653 (hereafter J1219), was identified, i.e., within the first two billion years of the age of the universe. Here we report the results obtained from a detailed broadband study of this peculiar source by analyzing the new ∼58 ksec XMM-Newtonand archival observations and reproducing the multiwavelength spectral energy distribution with the conventional one-zone leptonic radiative model. The XMM-Newtondata revealed that J1219 is a faint X-ray emitter (F0.3−10 keV=1.02−0.24+0.47×10−15ergcm−2s−1) and exhibits a soft spectrum (0.3−10 keV photon index=2.28−0.46+0.58). By comparing the broadband physical properties of J1219 with z>3γ-ray detected flat spectrum radio quasars (FSRQs), we have found that it has a relatively low jet power and, similar to FSRQs, the jet power is larger than the accretion disk luminosity. We conclude that deeper multiwavelength observations will be needed to fully explore the physical properties of this unique high-redshift BL Lac object.

Infections have a poor prognosis in inpatients with cirrhosis. We aimed to determine regional variations in infections and their association with clinical outcomes in a global cohort of inpatients with cirrhosis.

Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgent and unmet need for non‐invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease. Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity. Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = −1.161), MMRN1 (log2 FC = −1.982), MASP1 (log2 FC = −0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P= 1.07E‐09 and P= 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut‐off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity. Our results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease.

The catalytic activity and stability of sulfonic-based UiO-66(Zr) materials were tested in the Friedel–Crafts acylation of anisole with acetic anhydride. The materials were prepared using microwave-assisted synthesis, producing microporous materials with remarkable crystallinity and physicochemical features as acid catalysts. Different ratios between both organic ligands, terephthalic acid (H2BDC) and monosodium 2-sulfoterephthalic acid (H2BDC–SO3Na), were used for the synthesis to modulate the sulfonic content. The sulfonic-based UiO-66(Zr) material synthesized with a H2BDC/H2BDC–SO3Na molar ratio of 40/60 exhibited the best catalytic performance in the acidic-catalyzed Friedel–Crafts acylation reaction. This ratio balanced the number of sulfonic acid sites and their accessibility within the UiO-66 microporous structure. The catalytic performance of this material increased remarkably at 200 °C, outperforming reference acids and commercial heterogeneous catalysts such as Nafion-SAC-13 and Amberlyst-70. Additionally, the best sulfonic-based UiO-66(Zr) material proved to be stable in four successive reaction cycles, maintaining both its catalytic activity and its structural integrity.

Getting prompt insights about health and well-being in a non-invasive way is one of the most popular features available on wearable devices. Among all vital signs available, heart rate (HR) monitoring is one of the most important since other measurements are based on it. Real-time HR estimation in wearables mostly relies on photoplethysmography (PPG), which is a fair technique to handle such a task. However, PPG is vulnerable to motion artifacts (MA). As a consequence, the HR estimated from PPG signals is strongly affected during physical exercises. Different approaches have been proposed to deal with this problem, however, they struggle to handle exercises with strong movements, such as a running session. In this paper, we present a new method for HR estimation in wearables that uses an accelerometer signal and user demographics to support the HR prediction when the PPG signal is affected by motion artifacts. This algorithm requires a tiny memory allocation and allows on-device personalization since the model parameters are finetuned in real time during workout executions. Also, the model may predict HR for a few minutes without using a PPG, which represents a useful contribution to an HR estimation pipeline. We evaluate our model on five different exercise datasets – performed on treadmills and in outdoor environments – and the results show that our method can improve the coverage of a PPG-based HR estimator while keeping a similar error performance, which is particularly useful to improve user experience.

Humans are infected by Toxoplasma gondiiworldwide and its consequences may seriously affect an immune deprived population such as HIV and transplanted patients or pregnant women and foetuses. A deep knowledge of toxoplasmosis seroprevalence in Spain is needed in order to better shape health policies and educational programs. We present the results of the first systematic review and meta-analysis on the human prevalence for this disease in Spain. Databases (PubMed, Web of Science, SCOPUS and Teseo) were searched for relevant studies that were published between January 1993 and December 2023 and all population-based cross-sectional and longitudinal studies reporting the human seroprevalence in Spain were revised. Within the population analysed, our targeted groups were immunocompetent population, pregnant women and immunocompromised patients. Among 572 studies and 35 doctoral theses retrieved, 15 studies and three doctoral theses were included in the meta-analysis. A random effects model was used for the meta-analyses due to the high heterogeneity found between studies (I2: 99.97), since it is a statistically conservative model, in addition to allowing better external validity. The global pooled seroprevalence was 32.3% (95% CI 28.7–36.2%). Most of the studies carried out were in pregnant women and the meta-analysis reported that the pooled seroprevalence of toxoplasmosis in pregnant women in Spain was 24.4% (24,737/85,703, 95% CI 21.2–28.0%), based on the random effects model. It is recommended to continue monitoring the seroprevalence status of T. gondiiin order to obtain essential guidelines for the prevention and control of the infection in the population.

•M-CPE show high resistance rates to new β-lactam/β-lactamase inhibitor combinations.•Four possible transmission events between patients were identified.•Carbapenemase genes are usually located on different transmissible plasmids.•OXA-48-IncL plasmid cross-species transfer was found between and within patients.•Related or identical plasmids were found in CPE isolated prior to the M-CPE.

Este documento de consenso analiza el recorrido asistencial y emocional de los pacientes con psoriasis pustulosa generalizada (PPG), así como el recorrido deseable, detectando puntos críticos y traduciéndolos en necesidades y recomendaciones. A través de un enfoque multidisciplinar que involucró a un Comité Asesor (n=8), panel de expertos (n=15) y pacientes con PPG (n=6), se llevó a cabo este proyecto en 3fases. El recorrido de atención de estos pacientes resultó heterogéneo debido a variaciones en la enfermedad, modelos de atención y recursos disponibles, así como la carencia de guías de diagnóstico y tratamiento. Se han consensuado 45 recomendaciones para optimizar la atención y abordar el componente emocional de estos pacientes. Cinco de ellas se han destacado por su impacto y viabilidad. Así, se pone a disposición general una hoja de ruta de prioridades para mejorar el recorrido asistencial de los pacientes con PPG.

Twenty-one simplified analogues of the natural product domoic acid were designed, synthesized, and then characterized at homomeric kainic acid (KA) receptors (GluK1-3,5). LBG20304displays a high affinity for homomeric GluK5 receptors (IC50= 432 nM) with a >40-fold selectivity over homomeric GluK1-3 subtypes and ≫100-fold selectivity over native AMPA and N-methyl d-aspartate receptors. Functional studies of LBG20304on heteromeric GluK2/5 receptors show no agonist or antagonist functional response at 10 μM, while a concentration of 100 μM at neuronal slices (rat) shows low agonist activity. A molecular dynamics simulation of LBG20304, in a homology model of GluK5, suggests specific interactions with the GluK5 receptor and an occluded ligand binding domain, which is translated to agonist or partial agonist activity. LBG20304is a new compound for the study of the role and function of the KA receptors with the aim of understanding the involvement of these receptors in health and disease.

Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.

Plant-based diets have gained attention due to their beneficial effects against major chronic diseases, although their association with multimorbidity is mostly unknown.

Introduction/objectivesThe use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters.MethodsWe conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment.Results878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis.ConclusionnPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

ObjectivesSexual networks are known to structure sexually transmitted infection (STI) transmission among men who have sex with men (MSM). We sought to estimate the risks of STI diagnosis for various partnership types within these networks.MethodsOur cross-sectional survey analysed data from 1376 MSM screened for a partner management intervention in Lima, Peru. Participants were tested for HIV, syphilis, gonorrhoea (NG) and chlamydia (CT) and completed surveys on their demographics, sexual identity/role, HIV status, partnership types and sexual network from the prior 90 days. χ2and Wilcoxon rank-sum tests compared participants without an STI to those diagnosed with (1) syphilis, (2) NG and/or CT (NG/CT) and (3) syphilis and NG/CT coinfection (coinfection).Results40.8% (n=561/1376) of participants were diagnosed with an STI (syphilis: 14.9%, NG/CT: 16.4%, coinfection: 9.5%). 47.9% of all participants were living with HIV and 8.9% were newly diagnosed. A greater proportion of participants with syphilis and coinfection were living with HIV (73.5%, p<0.001; 71.0%, p<0.001) compared with those with NG/CT (47.8%) or no STI (37.8%). Participants with syphilis more often reported sex-on-premises venues (SOPVs) as the location of their last sexual encounter (51.7%, p=0.038) while those with NG/CT tended to meet their last sexual partner online (72.8%, p=0.031). Respondents with coinfection were the only STI group more likely to report transactional sex than participants without an STI (31.3%, p=0.039).ConclusionsSexual networks and partnership types of Peruvian MSM are associated with differential risks for STIs. Participants diagnosed with syphilis tended to meet single-encounter casual partners at SOPV, while MSM with NG/CT were younger and often contacted casual partners online. Coinfection had higher frequency of transactional sex. These findings suggest the potential importance of public health interventions through combined syphilis/HIV screening at SOPV, syphilis screening at routine clinic appointments for MSM living with HIV and directed advertisements and/or access to NG/CT testing through online platforms.

More than 1.2 billion tonnes of corn straw wastes (CSW) are generated worldwide each year. CSW is a fibrous, inexpensive, light material which is highly available. Currently, there are no pathways to manage such amount of CSW, being mainly burned in open field, with the environmental impact that this entails. In this work, the upcycling of CSW as a reinforcement material to be integrated in acrylonitrile-butadiene-styrene (ABS) composite matrix for additive manufacturing applications is proposed. ABS+CSW composite material has been used to manufacture 3D printing filaments, aiming to fabricate products via fused filament fabrication techniques. Standardized tensile and flexural test specimens were manufactured incorporating different contents of CSW (ranging from 1 to 5%, w/w) and glycerol (1%, w/w) to ABS: B1-1% (sample with 1% (w/w) of CSW), B2-3% (sample with 3% (w/w) of CSW), and B3-5% (sample with 5% (w/w) of CSW). The maximum tensile stress of the composites slightly increased by 1.3% (for B1-1%), exceeding 10% when B1-3% was used, compared to ABS. Moreover, it decreased to −3% for the specimen made with B3-5. In general terms, the higher the biomass content, the higher the flexural stress. However, the exception was provided by B1-1%, as the flexural stress decreased by 5% compared to ABS. The maximum flexural stress value was reached at 3% SCW, providing a value above 17%, compared to ABS and above 24%, compared to B1-1%. Furthermore, the incorporation of CSW into the ABS matrix resulted in lighter 3D printing filament materials and products compared to the use of ABS.

The divergence between the Andean fox (Lycalopex culpaeus) and the South American gray fox (L. griseus) represents a recent speciation event in South America. These taxa are partially sympatric and share biological, morphological, and ecological traits. Previous studies failed to recover reciprocal monophyly, suggesting the occurrence of introgression or incomplete lineage sorting (ILS). Here, we obtained mitochondrial and nuclear markers for 140 L. culpaeusand 134 L. griseusfrom the Southern Cone of South America to assess their inter and intraspecific divergence. We recovered reciprocal monophyly of L. culpaeusand L. griseus, with mild signatures of introgression or ILS. Therefore, taxonomic misidentification and the use of a limited number of markers may be the main reason behind the past debate about the delimitation of both species. Two main divergent clades were found in L. culpaeuswith a phylogeographical boundary in the High Plateau of northeastern Chile. The southern clade along with three northern sub-clades corresponded to four morphological subspecies. Less genetic differentiation was found in L. griseuswith a spatial population structure that does not support the occurrence of distinct subspecies. The results found in this study suggest the extant evolutionary significant units that need to be considered for biological conservation management of these species.

IntroductionManaging emergency situations in different simulated flight segments can entail a workload that could affect the performance of military pilots. The aim was to analyse the modifications in neurovegetative balance (using HR variability, HRV) of professional fighter pilots attending learning/training sessions on emergency situations in a flight simulator.MethodsA total of 18 pilots from the Spanish Air and Space Force were included. HRV was recorded simultaneously during diverse simulated emergency situations in three different flight segments: take-off, in-flight and landing.ResultsThe comparison between take-off and in-flight revealed a statistically significant increase (p<0.05) in percentage of consecutive RR intervals that differ by more than 50 ms from each other (pNN50), root mean square of the successive differences (rMSSD), standard desviation 1 and 2 (SD1 and SD2), and a statistically significant decrease (p<0.000) in stress score (SS) and in the sympathetic to parasympathetic ratio (S:PS). Between flight and landing, a statistically significant increase (p<0.05) in mean HR, minimum HR, maximum HR, SS and S:PS was shown, while experiencing a significant decrease (p<0.000) in pNN50, rMSSD and SD2. Finally, between take-off and landing, the variables which showed significant changes (p<0.05), with these changes being a significant increase, were mean HR, minimum HR, maximum HR, rMSSD, SD1 and SD2. SS and S:PS ratios showed a statistically significant decrease (p<0.000).ConclusionsAn emergency situation in a flight simulator manoeuvre produced an anticipatory anxiety response in pilots, demonstrated by low HRV, which increased during the flight segment and decreased during the landing segment of the flight.Trial registration numberNCT04487899.

Background subtraction (BS) is one of the first visual tasks in many video processing applications. In this work, we introduce a hardware adaptation of a top-ranked rule-based algorithm, the pixel-based adaptive segmenter (PBAS), implemented on an integrated circuit with on-focal plane processing. On average, our hardware-oriented PBAS (HO-PBAS) proposal features a similar algorithm performance to that of the original PBAS with the benefit of a reduced number of samples of the background model and linear equations, and thus a simpler overall model. This algorithm was implemented as a ${98} \times {98}$ pixels full-custom mixed-signal 180-nm standard CMOS vision sensor. This solution features in-pixel processing with resource sharing strategies and 47- $\mu \text{m}$ pixel pitch. The in-pixel processing includes the whole algorithm data path along with image preprocessing. The assessment of our implementation through ${F}$ -measure metrics with images captured by our chip from the public dataset changedetection shown on a PC screen results in a decrease of performance of only 6.7% with respect to the software version of PBAS.

Aging is the major risk factor for many metabolic chronic diseases. Several metabolic pathways suffer a progressive impairment during aging including body composition and insulin resistance which are associated to autophagy dysfunction and increased inflammation. Many of these alterations are aggravated by non-healthy lifestyle such as obesity and hypercaloric diet which have been shown to accelerate aging. Here, we show that the deleterious effect of hypercaloric diets is reverted by the NLRP3 inflammasome inhibition. NLRP3 deficiency extends mean lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by metabolic health benefits including reduced liver steatosis and cardiac damage, improved glucose and lipid metabolism, and improved protein expression profiles of SIRT-1, mTOR, autophagic flux, and apoptosis. These findings suggest that the suppression of NLRP3 prevented many age-associated changes in metabolism impaired by the effect of hypercaloric diets.

This article studies and improves the stability of a finite-difference time-domain (FDTD) subgridding method based on the orthogonalized-integral-based methodology. First, we identify the electric and magnetic field components of the FDTD lattices used at the interface between different mesh regions playing a critical role in its stability. Then, we use them to find a closed criterion for the Courant–Friedrichs–Lewy number (CFLN). Next, we analyze the stability by the classical spectral method and validate it with numerical heuristic simulations, proving the methodology used in the analytical approach. This information is used to devise a locally enlarged cell technique (LECT) to modify locally the scheme used to update the field components identified as most critical for stability so that an increased time step can be used. Finally, we analyze the effect of these modifications on the accuracy of the method for typical transmission and scattering problems.