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Abstract In the recent years, primordial black holes (PBHs) have emerged as one of the most interesting and hotly debated topics in cosmology. Among other possibilities, PBHs could explain both some of the signals from binary black hole mergers observed in gravitational-wave detectors and an important component of the dark matter in the Universe. Significant progress has been achieved both on the theory side and from the point of view of observations, including new models and more accurate calculations of PBH formation, evolution, clustering, merger rates, as well as new astrophysical and cosmological probes. In this work, we review, analyze and combine the latest developments in order to perform end-to-end calculations of the various gravitational-wave signatures of PBHs. Different ways to distinguish PBHs from stellar black holes are emphasized. Finally, we discuss their detectability with LISA, the first planned gravitational-wave observatory in space.

Teachers play a key role in students' learning, especially when it comes to students who have more difficulties in the classroom. Initial teacher training contributes to achieving more competent teachers who are capable of successfully facing the start of their teaching profession, and students' beliefs about what it means to be a good teacher are key. The prior beliefs and ideas with which future teachers come to university classrooms determine their first teaching identity and the beginning of their professional practice. In this paper, research focused on the beliefs of future secondary school teachers regarding what they consider constitutes a good teacher. A qualitative, biographical-descriptive methodology was used, in which the teaching students' narratives were used as a starting point to establish what characterizes a good teacher. The results show that future secondary school teachers place the relationship between the teacher and the students as the key factor when it comes to being a good teacher, above any other factor, which includes aspects related to the way in which the curriculum is taught.

Abstract Antigenically distinct SARS-CoV-2 variants increase the reinfection risk for vaccinated and previously exposed population due to antibody neutralization escape. COVID-19 severity depends on many variables, including host immune responses, which differ depending on genetic predisposition. To address this, we perform immune profiling of female mice with different genetic backgrounds –transgenic K18-hACE2 and wild-type 129S1– infected with the severe B.1.351, 30 days after exposure to the milder BA.1 or severe H1N1. Prior BA.1 infection protects against B.1.351-induced morbidity in K18-hACE2 but aggravates disease in 129S1. H1N1 protects against B.1.351-induced morbidity only in 129S1. Enhanced severity in B.1.351 re-infected 129S1 is characterized by an increase of IL-10, IL-1β, IL-18 and IFN-γ, while in K18-hACE2 the cytokine profile resembles naïve mice undergoing their first viral infection. Enhanced pathology during 129S1 reinfection cannot be attributed to weaker adaptive immune responses to BA.1. Infection with BA.1 causes long-term differential remodeling and transcriptional changes in the bronchioalveolar CD11c+ compartment. K18-hACE2 CD11c+ cells show a strong antiviral defense expression profile whereas 129S1 CD11c+ cells present a more pro-inflammatory response upon restimulation. In conclusion, BA.1 induces cross-reactive adaptive immune responses in K18-hACE2 and 129S1, but reinfection outcome correlates with differential CD11c+ cells responses in the alveolar space.

Abstract Background The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional throughout oxidative stress and inflammation, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases. Main body Maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. NRF2 is the main transcription factor that regulates cellular redox balance and inflammation-related gene expression. It has also demonstrated a potential role in regulating tight junction integrity and contributing to the inhibition of ECM remodeling, by reducing the expression of several metalloprotease family members involved in maintaining BBB function. Overall, we review current insights on the role of NRF2 in addressing protection against the effects of BBB dysfunction, discuss its involvement in BBB maintenance in different neuropathological diseases, as well as, some of its potential activators that have been used in vitro and in vivo animal models for preventing barrier dysfunction. Conclusions Thus, emerging evidence suggests that upregulation of NRF2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase its protection.

Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.

Abstract Background Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson’s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. Methods A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. Results Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1–3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. Conclusions The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. Trial registration NCT04017481.

Abstract Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression.

Introducción: El sueño es fundamental para la calidad de vida y puede afectar el bienestar y la salud mental de los individuos. Objetivo: Analizar la calidad del sueño y satisfacción laboral en enfermeras españolas tras la pandemia por COVID-19. Materiales y Métodos: Estudio transversal utilizando el Pittsburgh Sleep Quality Index (PSQI), el Cuestionario de Satisfacción Laboral Font Roja y variables sociodemográficas y laborales. Se empleó un muestreo en "bola de nieve" mediante divulgación en redes sociales. Resultados: La puntuación media del PSQI fue de 9,75 ± 4,36 puntos. La peor calidad del sueño se identificó en participantes sin personas a cargo (p=0,031;β=3,329;IC95%=0,035-6,354) y en aquellos con dependientes distintos de los hijos (p=0,022;β=4,121; IC95%= 0,575-7,667). Sin embargo, ser doctor (p=0,001; β=-3,406; IC95%=-5,503-1,309) o especialista (p=0,021; β=-1,639; IC95%=-3,031- -0,247) se asoció con una mayor calidad del sueño. La mejor satisfacción laboral se identificó en mujeres (p=0,034;β=0,104;IC95%=0,007-0,201), que no trabajaban con pacientes COVID (p=0,049;β=-0,085; IC95%=-0,174- -0,003). Discusión: Es crucial mejorar las condiciones laborales, como la ratio enfermera-paciente y la distribución de los turnos de trabajo, para mejorar la calidad del sueño de las enfermeras. Conclusiones: Las enfermeras españolas presentan una mala calidad del sueño. No tener personas a cargo y tener dependientes distintos de los hijos fueron factores de riesgo de mala calidad del sueño. La satisfacción laboral fue mayor en mujeres que no trabajaban con pacientes COVID-19. No se encontró relación entre la satisfacción laboral y la calidad del sueño de los trabajadores.

Background: Species hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management. Methods: A prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms. Results: A total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment. Conclusions: The presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.

The objective of this study was to demonstrate the possible correlation of visible carcass contamination and abattoir aerosol quality with microbial hygiene criteria. A total of 279 bovine carcasses were analyzed on 23 different working days. The aerobic colony count and total coliforms on the carcasses were calculated together with the presence of Escherichia coli. To determine the visible contamination of carcasses, we used a 100 cm2 sheet of transparent, adhesive plastic material, applied to the side of the carcass, to collect all the particles, which were then counted against both black and white backgrounds. The daily particulate index in the abattoir aerosol was determined using an air sampler device. The results showed that aerobic colony counts, which ranged from 1.41 to 2.40 log cfu cm−2, total coliforms (from 0.00 to 0.73 log cfu cm−2), and E. coli presence (from 0.00% to 60% of the sampled carcasses per day) are not correlated with the carcasses’ visual dirtiness or the aerosol quality. The factor analysis showed a correlation between the three groups of variables investigated: group 1, representing “aerosol quality”, group 2, representing the “microbiology of the carcass”, and group 3, the “visual dirtiness of the carcass”. Thus, even though microbiology analysis is useful in diagnosing the microorganisms which the official veterinarian is unable to detect during the post-mortem inspection, it is ineffective in evaluating slaughtering procedures. Aerosol monitoring and the visual classification of carcass dirtiness, instead, could provide good indications of the slaughtering process and the quality of the abattoir environment, and guarantee control of manufacturing practices, protecting both animals’ and operators’ health.

In recent years, advanced footwear technology (AFT) has been shown to improve performance in long-distance road running by altering biomechanics and perceived comfort. This type of footwear is now being marketed for mountain running, although its effects in such races remain unevaluated. This study aimed to examine the impact of AFT on performance, biomechanics, and perceived comfort during a simulated mountain running event. Twelve trained mountain runners participated in a 3-day experiment, with a 7-day recovery between sessions. On the first day, a maximal aerobic speed test assessed the runners’ performance levels. On the second day, participants familiarized themselves with a 5.19 km mountain circuit and comfort scale. On the third day, they completed two time trials on the same circuit, separated by 30 min of passive recovery, using conventional and AFT shoes in a randomized order. Physiological and biomechanical variables were recorded, including body mass, blood lactate, running biomechanics, vertical stiffness, shoe comfort, and rating of perceived exertion (RPE). The findings indicate that AFT does not improve performance or physiological responses during a simulated mountain race, regardless of segment (uphill, downhill, or mixed). However, AFT significantly alters running biomechanics, reducing step frequency and increasing the vertical oscillation of the center of gravity, especially in uphill and downhill sections. While overall comfort remained unchanged, specific differences were observed with AFT. Coaches and practitioners should consider these findings when using AFT in mountain running training or competition.

The recent astrometric data of hundreds of millions of stars from Gaia DR3 has allowed for a precise determination of the Milky Way rotation curve up to 28 kpc. The data suggest a rapid decline in the density of dark matter beyond 19 kpc. We fit the whole rotation curve with four components (gas, disk, bulge, and halo), and compute the microlensing optical depth to the Large Magellanic Cloud. With this model of the galaxy we reanalyse the microlensing events of the MACHO and EROS-2 Collaborations. Using the published MACHO efficiency function for the duration of their survey, together with the rate of expected events according to the new density profile, we find that the Dark Matter halo could be composed of up to 20% of massive compact halo objects for any mass between 0.001 to 1M⊙. For the EROS-2 survey, using a modified efficiency curve for consistency with the MACHO analysis, we also find compatibility with a MACHO halo, but with a tighter constraint around 0.005M⊙ where the halo fraction cannot be larger than ∼10%. This result assumes that all the lenses have the same mass. If these were distributed in an extended mass function like that of the Thermal History Model, the constraints are weakened, allowing 100% of all DM in the form of Primordial Black Holes.

The La Marcelina Formation (LMF) in the southern Deseado Massif area (c. 47° 55? S) represents a 23 m thick sedimentary succession deposited within a low-energy fluvial paleoenvironment. The age of this unit, formerly considered as Eocene due to its palynological assemblage, is adjusted by zircon U-Pb Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) from a sandstone bed at the middle part of the unit. The results reveal a maximum depositional age of ~20 Ma (Early Miocene, Burdigalian). The detrital zircon provenance analysis indicates zircon grains originated mostly in the Jurassic, with limited contributions from the Cretaceous, Permian, and Paleocene. The new age for LMF allows correlating these beds to the upper section of the continental Río Leona Formation in the southern Austral-Magallanes Basin.

Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.

Reseña del libro Memoria y Guerra Civil en la obra de Jorge Semprún (Madrid, Guillermo Escolar Editor, 2023), de Elios Mendieta. En el año del centenario del nacimiento de Jorge Semprún, una de las figuras más relevantes en el ámbito político y artístico del siglo XX, Elios Mendieta publica un excelente monográfico que enfoca la memoria, tema que domina ampliamente como puede observarse a través de su producción académica. Tanto para aquellos que pretendan conocer en profundidad la obra de Semprún como para los que se acercan al autor desde el ámbito de la investigación, el libro de Mendieta ofrece un estudio pormenorizado a la altura de una vida propia de un activista y humanista del calibre de Semprún. Asimismo, el libro reseñado no insiste en los numerosos estudios sobre los totalitarismos a los que se vio sometido Semprún, y más bien pone el foco sobre la influencia de la Guerra Civil Española en su producción, no tan estudiada; “la contienda de 1936 sobrevuela –o, incluso, toma una mayor relevancia–, ya sea como un recuerdo pretérito, como un objeto de reflexión, o incluso, como herida insalvable que no se puede despreciar” (12). Tras un repaso a la memoria de Semprún a través de su vida y obra, Mendieta incluye un minucioso análisis de Las dos memorias (1974), única película bajo la dirección del estudiado, y que no ha recibido la atención merecida por parte de la academia.

Tropical firewood species are of foremost importance for charcoal production worldwide. The objective of this study was to evaluate the impact of the moisture content of tropical fuelwood on charcoal production in modified Argentinean half-orange kilns in terms of yield, quality, and economic viability. Ten tropical species from the state of Quintana Roo, Mexico, were selected for charcoal production. The data were analyzed using a completely randomized design. The moisture content of the firewood was 48.99–79.31%. Temperatures close to 500 °C were obtained in the three kilns, as well as production yields of 28% with a consumption of 6.4 m3 of firewood and 38% with a consumption of 4.5–5 m3. Charcoal moisture values of less than 8%, volatile material of 20–30%, ash < 8%, fixed carbon of 60–70%, and higher heating values of 28–30 MJ kg−1 were obtained. Burn I obtained the highest energy yield of 54%, with a production of 20.87 MWh of charcoal recovered. The production cost of the kiln for the producer is USD 0.00825 (MXN 0.16) per MJ.