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Abstract Background Pulmonary arterial hypertension (PAH) is a severe disease characterized by elevated blood pressure in the pulmonary artery that can ultimately damage the right ventricle of the heart. PAH is pathophysiologically heterogeneous, which makes early diagnosis and treatment difficult. Inflammation is thought to be an important factor in the development and progression of this disease and may explain some of the observed interindividual differences. In the context of both acute and chronic inflammation, neutrophil recruitment to the lung has been suggested as a potential biomarker for studying PAH progression. However, there are currently no specific probes for its non-invasive in vivo detection. The imaging-based gold standard for assessing inflammation is [18F] fluorodeoxyglucose (18F-FDG), which is not cell specific. This highlights the urgent need for more specific molecular probes to support personalized medicine. Methods This study investigated the potential of magnetic nanoradiotracers based on ultrasmall iron oxide nanoparticles, functionalized with N-cinnamoyl-F-(D)L-F-(D)L-F peptide, to detect increased neutrophil infiltration in vivo in different PAH animal models via positron emission tomography. These nanoprobes target formyl peptide receptor 1, which is abundantly expressed in the cell membrane of neutrophils. To assess the benefit of these nanoprobes, their biodistribution was first assessed via magnetic resonance imaging and histology. Then, their lung uptake was compared by positron emission tomography with that of 18F-FDG in two types of PAH animal models with different profiles of inflammation and neutrophil infiltration: monocrotaline and double-hit Sugen-chronic hypoxia PAH rat models. Results Our targeted magnetic nanoradiotracer detected an increase in pulmonary neutrophil infiltration in both PAH models and distinguished between them, which was not possible with 18F-FDG PET. Conclusions This study underscores the importance of targeted imaging in providing an individualized and longitudinal evaluation of heterogeneous and multifactorial diseases such as PAH. The use of targeted multimodal nanoprobes, for magnetic resonance/positron emission tomography imaging has the potential to facilitate the diagnosis and monitoring of diseases, as well as the development of novel therapies. Graphical abstract

Abstract Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.

The machining of implants and parts for dental prostheses to eliminate biofilm in the implantoplasty process causes a loss of mechanical properties and also characteristics of the surfaces, making tissue regeneration difficult. In the present work, treatments consisting of elements that can reduce infection, such as citric acid and magnesium, together with elements that can improve cell adhesion and proliferation, such as collagen, are proposed for implant–crown assembly. Titanium, zirconia, composite (PMMA + feldspar) and cobalt–chromium discs were immersed in four different solutions: 25% citric acid, 25% citric acid with the addition of collagen 0.25 g/L, 25% citric acid with the addition of 0.50 g/L and the latter with the addition of 1% Mg (NO3)2. After immersion was applied for 2 and 10 min, the roughness was determined by interferometric microscopy and the contact angle (CA) was evaluated. Human fibroblastic and osteoblastic line cells (HFFs and SaOS-2) were used to determine cell viability and proliferation capacity. Cell binding and cytotoxicity were determined by resazurin sodium salt assay (Alamar Blue) and cell morphology by confocal assay (immunofluorescence F-actin (phalloidin)) after 3 days of incubation. For the evaluation of bacterial activity, the bacterial strains Sptreptococcus gordonii (Gram+) and Pseudomonas aeruginosa (Gram−) were used. The antibacterial properties of the proposed treatments were determined by means of the resazurin sodium salt (Alamar Blue) assay after 1 day of incubation. The treatments considerably decreased the contact angle of the treated samples with respect to the control samples. The treatments endowed the surfaces of the samples with a hydrophilic/super-hydrophilic character. The combination of elements proposed for this study provided cell viability greater than 70%; considering the absence of cytotoxicity, it therefore promotes the adhesion and proliferation of fibroblasts and osteoblasts. In addition, it also endows the surface with antibacterial characteristics against from Gram+ and Gram− bacteria without damaging the cells. These results show that this mouthwash can be useful in oral applications to produce a new passivation layer that favors the hydrophilicity of the surface and promotes cellular activity for the formation of fibroblasts and osteoblasts, as well as showing bactericidal activity.

El infoshow es el macrogénero de mayor crecimiento a nivel global durante las últimas décadas. Esto se debe, en gran medida, a los procesos de desregulación de los mercados televisivos, que han fomentado que los contenidos se adapten cada vez más a los gustos y demandas de la audiencia. En España, el auge del infoshow comenzó en la década de los 2000, en un contexto de crisis económica y desafección política que propició un mayor interés del público general por temas económicos, sociales y políticos, todos ellos muy propicios a la crítica y la espectacularización. En este contexto, la sátira de actualidad se consolidó como un género destacado en la televisión española. Esta investigación se centra en El Intermedio, producido por Globomedia para La Sexta. Este programa formaba parte de los primeros contenidos con los que la cadena inició sus emisiones oficiales, en el año 2006, y sigue presente en su prime time dieciocho años después. Se trata, sin duda, del programa más longevo y, también, uno de los de mayor éxito de su parrilla. Aunque sigue la tradición de formatos previos, El Intermedio ofrece un enfoque innovador alejándose del ámbito puramente humorístico para ofrecer un acercamiento alternativo a las noticias de actualidad. Mediante el análisis de contenido de sus diez primeras temporadas se analiza el perfil de sus presentadores y colaboradores y su estructura de contenidos. Los resultados muestran un enfoque innovador en el tratamiento de las noticias y en el equilibrio entre la función informativa y el entretenimiento.

Abstract Rhythmic entrainment is a fundamental aspect of musical behavior, but the skills required to accurately synchronize movement to the beat seem to develop over many years. Motion capture studies of corporeal synchronization have shown immature abilities to lock in to the beat in children before age 5, and reliable synchronization ability in adults without musical training; yet there is a lack of data on full-body synchronization skills between early childhood and adulthood. To document typical rhythmic synchronization during middle childhood, we used a wireless motion capture device to measure period- and phase-locking of full body movement to rhythm and metronome stimuli in 6 to 11 year-old children in comparison with adult data. Results show a gradual improvement with age; however children’s performance did not reach adult levels by age 12, suggesting that these skills continue to develop during adolescence. Our results suggest that in the absence of specific music training, full-body rhythmic entrainment skills improve gradually during middle childhood, and provide metrics for examining the continued maturation of these skills during adolescence.

Abstract TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer’s disease, Huntington’s disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

Abstract Arguably, the greatest threat to bacteria is phages. It is often assumed that those bacteria that escape phage infection have mutated or utilized phage‐defence systems; however, another possibility is that a subpopulation forms the dormant persister state in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently. Slower growth and dormancy play a key physiological role as they allow host phage defence systems more time to clear the phage infection. Here, we investigated how bacteria survive lytic phage infection by isolating surviving cells from the plaques of T2, T4, and lambda (cI mutant) virulent phages and sequencing their genomes. We found that bacteria in plaques can escape phage attack both by mutation (i.e. become resistant) and without mutation (i.e. become persistent). Specifically, whereas T4‐resistant and lambda‐resistant bacteria with over a 100,000‐fold less sensitivity were isolated from plaques with obvious genetic mutations (e.g. causing mucoidy), cells were also found after T2 infection that undergo no significant mutation, retain wild‐type phage sensitivity, and survive lethal doses of antibiotics. Corroborating this, adding T2 phage to persister cells resulted in 137,000‐fold more survival compared to that of addition to exponentially growing cells. Furthermore, our results seem general in that phage treatments with Klebsiella pneumonia and Pseudomonas aeruginosa also generated persister cells. Hence, along with resistant strains, bacteria also form persister cells during phage infection.

BackgroundMultidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms.ResultsCinnamaldehyde (CAD) was added to K. pneumoniae cultures to inhibit QS and thus demonstrate the role of the signaling system in regulating the anti-phage defense mechanism. The QS inhibitory activity of CAD in K. pneumoniae was confirmed by a reduction in the quantitative expression of the lsrB gene (AI-2 pathway) and by proteomic analysis. The infection assays showed that the phage was able to infect a previously resistant K. pneumoniae strain in the cultures to which CAD was added. The results were confirmed using proteomic analysis. Thus, anti-phage defense-related proteins from different systems, such as cyclic oligonucleotide-based bacterial anti-phage signaling systems (CBASS), restriction–modification (R–M) systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, and bacteriophage control infection (BCI), were present in the cultures with phage but not in the cultures with phage and CAD. When the QS and anti-phage defense systems were inhibited by the combined treatment, proteins related to phage infection and proliferation, such as the tail fiber protein, the cell division protein DamX, and the outer membrane channel protein TolC, were detected.ConclusionInhibition of QS reduces phage resistance in K. pneumoniae, resulting in the infection of a previously resistant strain by phage, with a significant increase in phage proliferation and a significant reduction in bacterial growth. QS inhibitors could be considered for therapeutic application by including them in phage cocktails or in phage-antibiotic combinations to enhance synergistic effects and reduce the emergence of antimicrobial resistance.

The resonant dynamic of a magnetic domain wall in a permalloy microstrip has been investigated using an innovative experimental setup that enables a simultaneous measurement of the ferromagnetic resonance and the magnetoresistance. The resonance frequency associated with the presence of the magnetic domain wall increases linearly with the external magnetic field in the range of fields where the domain wall is present in the microstrip. This linear behavior is unusual in a domain wall and not related to the standard resonant modes of a magnetic domain wall, such as breathing, twisting, or translational modes. The slope of this linear dependency is 1.38 GHz/mT, which is an incredibly large value and allows the detection of very small changes in the external magnetic field. This linear behavior opens a path for developing a highly tunable radio frequency oscillator or a magnetic sensing device where the presence of an external field is detected via small variations in the resonant frequency of the domain wall.

This pioneering work studied the medieval color palette of four manuscripts produced in the scriptorium of Alfonso X, king of the Crown of Castile (r. 1252-84), including the Songs of Holy Mary (Cantigas de Santa Maria, in Rich Codex and Musicians’ Codex), Lapidary (Lapidario), and Book of Games (Libro de los juegos). Scientific analysis based on fiber-optics reflectance spectroscopy in the visible and Raman spectroscopy showed a color palette based on lapis lazuli, indigo, azurite, vermilion, red lead, orpiment, yellow ochre, two different greens (bottle green and vergaut), lead white, carbon-based black, and most importantly, brazilwood pinks, reds, and purples. So, it is now the first reported use of this lake pigment in European medieval manuscript illumination. The painting technique is also discussed. The diversity of colors and techniques, with the presence of lapis lazuli, brazilwood lake pigments, purple, and gold, demonstrates Alfonso X’s desire to produce sumptuous manuscripts.

This study examines the potential of fungal chitosan derived from Aspergillus niger as a sustainable alternative to traditional petrochemical-based ingredients in cosmetic products. Specifically, the research examines the solubility of fungal chitosan in aqueous solutions of varying ionic strength and its adsorption onto negatively charged surfaces that mimic human hair keratin. The adsorption behavior, water content, and frictional properties of chitosan films were evaluated using a quartz crystal microbalance with dissipation monitoring and a surface force apparatus (SFA). The findings indicated that fungal chitosan exhibits good solubility at a pH of 4.5. Conversely, the adsorption of chitosan is subject to the influence of both polymer concentration and ionic strength. At the lowest ionic strengths, a screening-enhanced adsorption process occurs as a consequence of the reduction in chitosan solubility in the presence of salt. This results in the depletion of polymer chains from the solution and their subsequent deposition. An increase in ionic strength above 15–20 mM results in a worsening of the chitosan–surface interaction, due to the simultaneous screening of both the chitosan and the surface charges. This results in a hindrance to the adsorption process. The deposited films are highly hydrated, and this hydration increases with both polymer concentration and ionic strength. Furthermore, the films exhibit a predominantly elastic behavior, and the response of the films under shear deformations shows a strong dependence on the polymer concentration. These findings contribute to the development of environmentally friendly cosmetic formulations that meet consumer demands for sustainability.

The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.

Background: Pretreatment assessment of patients diagnosed with localized prostate cancer (PCa) is essential for therapeutic decision-making. Currently available staging systems based on prostate-specific antigen (PSA), Gleason score, and clinical stage allow for determining the prognostic characteristics of these patients. Several studies have evaluated the preoperative use of prostate-specific antigen density (PSAD) as a prognostic factor for further risk stratification. To date, the role of PSAD in this setting is still an object of debate. Objectives: The present analysis aimed to assess the predictive potential of PSAD for adverse oncological outcomes after robot-assisted radical prostatectomy (RARP) and to compare its accuracy to preoperative PSA (pPSA). Design and methods: We retrospectively reviewed 427 patients diagnosed with localized PCa who underwent RARP at a single institution between January 2015 and January 2020. Generating receiver operator characteristic (ROC) curves, calculating areas under the curves (AUCs), and using a linear regression model, we analyzed the association of PSAD and pPSA with postoperative positive surgical margins (PSM), Gleason score ⩾ 7, persistent PSA, and biochemical recurrence (BCR), with a median follow-up of 47 months. Results: PSAD showed a significant association with PSM ( p

ABSTRACTAlthough toxin/antitoxin (TA) systems are ubiquitous, beyond phage inhibition and mobile element stabilization, their role in host metabolism is obscure. One of the best-characterized TA systems is MqsR/MqsA of Escherichia coli, which has been linked previously to protecting gastrointestinal species during the stress it encounters from the bile salt deoxycholate as it colonizes humans. However, some recent whole-population studies have challenged the role of toxins such as MqsR in bacterial physiology since the mqsRA locus is induced over a hundred-fold during stress, but a phenotype was not found upon its deletion. Here, we investigate further the role of MqsR/MqsA by utilizing single cells and demonstrate that upon oxidative stress, the TA system MqsR/MqsA has a heterogeneous effect on the transcriptome of single cells. Furthermore, we discovered that MqsR activation leads to induction of the poorly characterized yfjXY ypjJ yfjZF operon of cryptic prophage CP4-57. Moreover, deletion of yfjY makes the cells sensitive to H2O2, acid, and heat stress, and this phenotype was complemented. Hence, we recommend yfjY be renamed to lfgB (less fatality gene B). Critically, MqsA represses lfgB by binding the operon promoter, and LfgB is a protease that degrades MqsA to derepress rpoS and facilitate the stress response. Therefore, the MqsR/MqsA TA system facilitates the stress response through cryptic phage protease LfgB.IMPORTANCEThe roles of toxin/antitoxin systems in cell physiology are few and include phage inhibition and stabilization of genetic elements; yet, to date, there are no single-transcriptome studies for toxin/antitoxin systems and few insights for prokaryotes from this novel technique. Therefore, our results with this technique are important since we discover and characterize a cryptic prophage protease that is regulated by the MqsR/MqsA toxin/antitoxin system in order to regulate the host response to oxidative stress.

Resumen Introducción y objetivo. Los reimplantes, salvo excepciones, son mejor solución para las amputaciones que la revisión del muñón, especialmente en miembro superior. En un contexto de optimización de resultados, es esencial la autoevaluación. Por ello, el objetivo del presente estudio es recoger los resultados funcionales (incluyendo variables objetivas y subjetivas) de los reimplantes realizados en nuestro Servicio de Cirugía Plástica del Hospital Universitario Central de Asturias (España) en la última década. Material y método. Evaluamos los resultados de los reimplantes realizados en nuestro servicio desde 2010 usando una sistemática similar a la empleada para una serie de casos analizada entre 2000 y 2009. Así, presentamos los resultados funcionales objetivos en rango articular, fuerza de prensión y discriminación sensitiva usando la Tabla de Mayo Modificada para amputaciones distales a muñeca y los Criterios de Chen para las proximales. Evaluamos los resultados subjetivos con el Cuestionario de Russell. Resultados. Desde enero de 2010 se realizaron 37 intentos de reimplante de miembro superior, 6 de ellos en 2021 (excluidos del análisis global). El 83.87% fueron distales a muñeca (la mayoría con afectación del 1er dedo) y el 48.39% accidentes laborales. La mayoría de las lesiones fueron por maquinaria cortante. La supervivencia global de los fragmentos reimplantados fue del 75%, con necrosis parciales y rigideces como principales complicaciones. El resultado medio fue aceptable, con algunos buenos resultados (la mayoría pulgares). Tuvimos 2 casos proximales con buenos resultados. La satisfacción de los pacientes fue mayor que en aquellos amputados. Todos menos 1 recomendarían el procedimiento. Conclusiones. Los reimplantes son procedimientos complejos que, bien indicados, suponen un tratamiento óptimo en lesiones mutilantes de miembro superior y es el preferido por nuestros pacientes frente a la amputación. Nuestros resultados, con un número decreciente de procedimientos, son aceptables, mejores en lesiones de 1er dedo. La mayoría de los pacientes usan su mano para casi todas sus actividades, mostrándose satisfechos con el resultado.

Abstract This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

The main goal of the current work was to assess the age sensitivity of a novel battery of cool and hot Executive Function (EF) tasks developed for the middle childhood period: the Executive Brain Battery (EBB). To this end, we carried out a first study in which the EBB was administered to six age groups ranging from 6 to 11. Additionally, in a second study, we compared children at the end of middle childhood (age 11 years) and adult performance in the EBB. Results showed that tasks included in the EBB were suitable for all age groups, with more age-related changes being found in cool than hot EF tasks. Moreover, at the end of middle childhood, children reach an adult-like performance in most of these cool and hot tasks. The present findings extend previous research suggesting that cool and hot EFs exhibit different patterns of age-related growth in middle childhood. Additionally, the EEB could become a useful tool for research on EFs during middle childhood that could be adapted for a wide range of populations.

Los recursos humanos capaces de brindar cuidados formales de largo plazo para personas mayores son una demanda creciente en Latinoamérica. En la región, existe déficit formativo en las personas cuidadoras, por lo que los gobiernos plantean la capacitación como prioridad, al desarrollar sus sistemas de cuidados. El objetivo del estudio es analizar los contenidos incluidos en los programas formativos técnicos, ofrecidos en Colombia, Costa Rica y Uruguay y compararlos con las necesidades e intereses educativos reportados por quienes cuidan, así como con programas de estudio y formaciones que incorporan el enfoque de atención centrada en la persona a nivel internacional. Estudio descriptivo, a través de un estudio mixto, aplicando una estrategia concurrente de triangulación de datos cualitativos y cuantitativos. Se realizó revisión documental de ocho planes de estudio en cuidados de los tres países para identificar contenidos y se encuestó a 109 personas cuidadoras entre noviembre 2021 y marzo 2022, consultando acerca de condiciones laborales, retos e intereses formativos. Los contenidos identificados, se organizaron en torno a cinco dimensiones que transversalizan el enfoque de Atención Centrada en las Personas. Se identificó mayor representación de temáticas asociadas a aprender competencias para el cuidado sanitario y establecer rutinas de cuidado cotidiano, que, para el trato humanizado y el desarrollo de planes personalizados con la persona mayor, aunque estos últimos fueron de los más mencionados por quienes cuidan. Se requieren más estudios para conocer intereses formativos de quienes cuidan, así como para profundizar en programas de más países de la región.

ABSTRACT Myriad bacterial anti-phage systems have been described and often the mechanism of programmed cell death is invoked for phage inhibition. However, there is little evidence of “suicide” under physiological conditions for these systems. Instead of death to stop phage propagation, we show here that persister cells, i.e., transiently-tolerant, dormant, antibiotic-insensitive cells, are formed and survive using the Escherichia coli C496_10 tripartite toxin/antitoxin system MqsR/MqsA/MqsC to inhibit T2 phage. Specifically, MqsR/MqsA/MqsC inhibited T2 phage by 105-fold and reduced T2 titers by 3,000-fold. During T2 phage attack, in the presence of MqsR/MqsA/MqsC, evidence of persistence includes the single-cell physiological change of reduced metabolism (via flow cytometry), increased spherical morphology (via transmission electron microscopy), and heterogeneous resuscitation. Critically, we found restriction-modification systems (primarily EcoK McrBC) work in concert with the toxin/antitoxin system to inactivate phage, likely while the cells are in the persister state. Hence, a phage attack invokes a stress response similar to antibiotics, starvation, and oxidation, which leads to persistence, and this dormant state likely allows restriction/modification systems to clear phage DNA. IMPORTANCE To date, there are no reports of phage infection-inducing persistence. Therefore, our results are important since we show for the first time that a phage-defense system, the MqsRAC toxin/antitoxin system, allows the host to survive infection by forming persister cells, rather than inducing cell suicide. Moreover, we demonstrate that the MqsRAC system works in concert with restriction/modification systems. These results imply that if phage therapy is to be successful, anti-persister compounds need to be administered along with phages.

El estado de investigación actual muestra cómo los centros de educación secundaria acostumbran a prohibir o limitar el uso del teléfono móvil. Delante de las conductas de riesgo en el mundo virtual comúnmente conocidas, se necesita indagar en nuevos modelos pedagógicos para la inclusión del dispositivo en consecución de las Competencias Digitales y curriculares. El artículo tiene como finalidad plantear posibilidades y limitaciones para la inclusión del teléfono móvil en los centros, considerando el enfoque del Desarrollo Positivo Adolescente. Se ha desarrollado una revisión de la literatura y se consideran hallazgos de investigaciones previas. La inclusión del dispositivo desde el enfoque del DPA implica generar nuevas acciones educativas para el logro de las competencias, considerando las potencialidades, empoderamiento y participación del alumnado en beneficio de sus relaciones, su bienestar, la construcción de su identidad y su autonomía progresiva. El artículo concreta “6 Interrogantes para la inclusión del Teléfono Móvil en centros de educación secundaria desde el Enfoque del Desarrollo Positivo Adolescente”, pretendiendo abrir nuevos caminos en el establecimiento de modelos tecno-pedagógicos innovadores que posibiliten incluir la tecnología en el sistema educativo en beneficio del desarrollo integral del alumnado.

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage.

In the last few years, archaeoacoustic studies of rock art sites and landscapes have undergone significant growth as a result of renewed interest in the intangible aspects of the archaeological record. This article focuses on the acoustic study carried out in the rock art complex of Bacinete, Cádiz (Spain). After describing the archaeological site and its importance, a representative set of monaural and spatial IRs gathered onsite is thoroughly analysed to explore the hypothesis that the sonic component of the site played an important role in how prehistoric people interacted with it. Additionally, we briefly discuss the challenges of analysing the acoustics of open-air spaces following the recommendations of the ISO 3382-1 guidelines, a standard developed not for open-air spaces, but for room acoustics. The results obtained confirm the favourable acoustic conditions of the Bacinete main shelter for speech transmission. The different subjective acoustic impressions obtained in a somewhat similar shelter located nearby, Bacinete III, are also explained, alluding to a lesser degree of intimacy felt in the latter.

Abstract Background Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 receptor agonist, is approved in the United States, Europe and Japan for the treatment of type 2 diabetes. Across the SURPASS-1 to -5 clinical studies, tirzepatide 5, 10 and 15 mg demonstrated significant improvements in glycated haemoglobin A1c (HbA1c) (− 1.9 to − 2.6%), body weight (− 6.6 to − 13.9%) and systolic blood pressure (SBP) (− 2.8 to − 12.6 mmHg) at the end of study treatment. Methods Post-hoc mediation analyses were conducted to evaluate weight-loss dependent and weight-loss independent effects of tirzepatide on SBP reductions across the 5 SURPASS studies. The safety population (all randomized patients who took at least 1 dose of study drug) of each study was analyzed. Additional analyses were conducted at individual study level or pooled across 5 SURPASS trials. Results The difference in mean SBP change from baseline at 40 weeks (total effect) between the tirzepatide and comparator groups was − 1.3 to − 5.1 mmHg (tirzepatide 5 mg), − 1.7 to − 6.5 mmHg (tirzepatide 10 mg) and − 3.1 to − 11.5 mmHg (tirzepatide 15 mg). These SBP reductions were primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. In the SURPASS-4 study, which enrolled patients with established cardiovascular disease, weight-loss independent effects explained 33% to 57% of difference in SBP change between tirzepatide and insulin glargine groups. In a pooled analysis of the SURPASS-1 to -5 studies, there was a significant (p 140 mmHg), while those in the first quartile of baseline SBP category (

Abstract Phage tail-like bacteriocins (PTLBs) are large proteomic structures similar to the tail phages. These structures function in bacterial competition by making pores in the membrane of their competitors. The PTLBs identified in Pseudomonas aeruginosa are known as R-type and F-type pyocins, which have a narrow spectrum of action. Their specificity is determined by the tail fiber and is closely related to the lipopolysaccharide type of the target competitor strain. In this study, the genome sequences of 32 clinical of P. aeruginosa clinical isolates were analysed to investigate the presence of R-type and F-type pyocins, and one was detected in all strains tested. The pyocins were classified into 4 groups on the basis of the tail fiber and also the homology, phylogeny and structure of the cluster components. A relationship was established between these groups and the sequence type and serotype of the strain of origin and finally the killing spectrum of the representative pyocins was determined showing a variable range of activity between 0 and 37.5%. The findings showed that these pyocins could potentially be used for typing of P. aeruginosa clinical isolates, on the basis of their genomic sequence and cluster structure, and also as antimicrobial agents.

Mucins are important glycoproteins that form a protective layer throughout the gastrointestinal and respiratory tracts. There is scientific evidence of increase in phage-resistance in the presence of mucin for some bacterial pathogens. Manipulation in mucin composition may ultimately influence the effectiveness of phage therapy. In this work, two clinical strains of K. pneumoniae (K3574 and K3325), were exposed to the lytic bacteriophage vB_KpnS-VAC35 in the presence and absence of mucin on a long-term co-evolution assay, in an attempt to mimic in vitro the exposure to mucins that bacteria and their phages face in vivo. Enumerations of the bacterial and phage counts at regular time intervals were conducted, and extraction of the genomic DNA of co-evolved bacteria to the phage, the mucin and both was performed. We determined the frequency of phage-resistant mutants in the presence and absence of mucin and including a mucolytic agent (N-acetyl L-cysteine, NAC), and sequenced them using Nanopore. We phenotypically demonstrated that the presence of mucin induces the emergence of bacterial resistance against lytic phages, effectively decreased in the presence of NAC. In addition, the genomic analysis revealed some of the genes relevant to the development of phage resistance in long-term co-evolution, with a special focus on the mucoid environment. Genes involved in the metabolism of carbohydrates were mutated in the presence of mucin. In conclusion, the use of mucolytic agents prior to the administration of lytic phages could be an interesting therapeutic option when addressing K. pneumoniae infections in environments where mucin is overproduced.

El objetivo de este artículo es describir el proceso de diseño y producción interdisciplinar de un OET ejemplo de una Práctica Educativa Abierta (PEA), diseñado y producido desde un contexto de educación superior que contribuye a la formación permanente de profesionales de la educación con recursos educativos desarrollados con criterios de calidad educativa y científica. Bajo el enfoque metodológico de la Investigación Basada en el Diseño (IBD), se presenta el proceso de desarrollo tecno-pedagógico, los principios que han guiado su diseño y producción, así como la descripción del resultado final. El resultado es el OET Teenpods, que trata sobre temáticas relacionadas con el enfoque del Desarrollo Positivo Adolescente (DPA) y los Objetivos de Desarrollo Sostenible (ODS). El estudio, cuestiona los límites de educación formal y superior, no formal e informal; reflexiona sobre la transversalidad y utilidad de la educación transmedia como estrategia para generar PEA que fomenten la formación autodirigida de los profesionales de la educación a través de su participación, agencia y empoderamiento; y proporciona directrices y orientaciones para generar prácticas y Recursos Educativos Abiertos (REA) de calidad en la era digital.

IntroductionBacteria must combat phages, and myriad bacterial anti-phage systems have been discovered that reduce host metabolism, for example, by depleting energetic compounds like ATP and NAD+. Hence, these systems indirectly inhibit protein production. Surprisingly, direct reduction of ribosome activity has not been demonstrated to thwart phage.MethodsHere, by producing each of the 4,287 Escherichia coli proteins and selecting for anti-phage activity that leads to enhanced growth, we investigated the role of host proteins in phage inhibition.Results and discussionWe identified that E. coli GTPase RsgA inhibits lytic phage T4 by inactivating ribosomes.

ABSTRACT Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated. This technology is usually combined with isothermal pre-amplification reactions in order to increase its sensitivity. We have developed a new LAMP-CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for nucleic acid purification and concentration. To evaluate the assay, we used 68 OXA-48-like-producing Klebsiella pneumoniae clinical isolates as well as 64 Enterobacter cloacae complex GES-6, 14 Pseudomonas aeruginosa GES-5, 9 Serratia marcescens GES-6, 5 P. aeruginosa GES-6, and 3 P. aeruginosa (GES-15, GES-27, and GES-40) and 1 K. pneumoniae GES-2 isolates. The assay, which takes less than 2 h and costs approximately 10 € per reaction, exhibited 100% specificity and sensitivity (99% confidence interval [CI]) for both OXA-48 and all GES carbapenemases. IMPORTANCE Carbapenems are one of the last-resort antibiotics for defense against multidrug-resistant pathogens. Multiple nucleic acid amplification methods, including multiplex PCR, multiplex loop-mediated isothermal amplification (LAMP) and multiplex RPAs, can achieve rapid, accurate, and simultaneous detection of several resistance genes to carbapenems in a single reaction. However, these assays need thermal cycling steps and specialized instruments, giving them limited application in the field. In this work, we adapted with high specificity and sensitivity values, a new LAMP CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for RNA extraction.

A commercial olive leaf extract (OL), effective against Salmonella enterica, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, was added to three different coating formulations (methylcellulose, MC; chitosan, CT; and alginate, ALG) to produce active polylactic acid (PLA) coated films. Evaluation of these coated PLA films revealed significant inhibition of S. aureus growth, particularly with the MC and CT formulations exhibiting the highest inhibition rates (99.7%). The coated films were then tested for food contact compatibility with three food simulants (A: 10% ethanol; B: 3% acetic acid; D2: olive oil), selected to assess their suitability for pre-cut hams and ready-to-eat vegetables in relation to overall migration. However, coated films with active functions exhibited migration values in simulants A and B above legal limits, while promising results were obtained for simulant D2, highlighting the need to deeply investigate these coatings’ impact on a real food system. Untargeted metabolomics revealed that the type of coating influenced the selective release of certain phenolic classes based on the food simulant tested. The Oxitest analysis of simulant D2 demonstrated that the MC and ALG-coated PLA films slightly slowed down the oxidation of this food simulant, which is an edible vegetable oil.

We examine the press representation of monk parakeets (Myiopsitta monachus) and their population management in Madrid city. To do this, we analyze mentions of this species in six Spanish newspapers for the case of Madrid. We apply a mixed methodology composed of framing, text analysis, and sentiment analysis. This multi-method approach allows us to further examine the framing and word choice of the newspapers, concluding that the press representation of monk parakeets has been biased and non-ethically led. We discuss this outcome by proposing a media representation guided by non-speciesist ethical framings and avoiding the objectification of nonhuman animals.

Abstract The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p

Abstract Since their discovery, toxin-antitoxin (TA) systems have captivated the attention of many scientists. Recent studies have demonstrated that TA systems play a key role in phage inhibition. The aim of the present study was to investigate the role of the PemIK (PemK/PemI) type II TA system in phage inhibition by its intrinsic expression in clinical strains of Klebsiella pneumoniae carrying the lncL plasmid, which harbours the carbapenemase OXA-48 and the PemK/PemI TA system. Furthermore, induced expression of the system in an IPTG-inducible plasmid in a reference strain of K. pneumoniae ATCC10031 was also studied. The results showed that induced expression of the whole TA system did not inhibit phage infection, whereas overexpression of the pemK toxin prevented early infection. To investigate the molecular mechanism involved in the PemK toxin-mediated inhibition of phage infection, assays measuring metabolic activity and viability were performed, revealing that overexpression of the PemK toxin led to dormancy of the bacteria. Thus, we demonstrate that the PemK/PemI TA system plays a role in phage infection and that the action of the free toxin induces a dormant state in the cells, resulting in inhibition of phage infections.

PurposeThe present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences.MethodsWe carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed.ResultsEighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p< 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of

Esta investigación analiza el impacto que ha tenido el estreno único de Netflix en las dinámicas propias de la serialidad. La digitalización de la televisión ha modificado profundamente el medio y el binge watching y el abandono del estreno semanal han cambiado por completo el consumo y la creación de ficciones. Para abordar esta cuestión, se analizan las cuatro series documentales que ha producido la compañía en España: Examen de conciencia (2019), El caso Alcàsser (2019), La Línea: La sombra del narco (2020) y Nevenka (2021). Al eliminar la espera entre los episodios las tramas capitulares desbordan la entrega y los seriales no siguen los patrones vinculados a la especulación. Consecuentemente, las entregas pierden su unidad formal o, directamente, se abandona la serialidad como modelo narrativo. Este cambio de paradigma refuerza la idea de que, al modificar la metodología de distribución, también se alteran las características sintácticas de los productos.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders that lead to photoreceptor loss. RP has been reported to be related to oxidative stress, autophagy, and inflammation. (-)-Epigallocatechin gallate (EGCG), the most abundant catechin-based flavonoid in green tea leaves, has significant antioxidant, anti-carcinogenic, antimicrobial, and neuroprotective properties. EGCG, given its low molecular weight and hydrophilic properties, can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens, cornea, and retina. EGCG has been shown to provide retinal protection against ischemia; sodium nitroprusside-, N-methyl-D-aspartate-, lipopolysaccharide-, light-, sodium iodate-, or H2O2-induced damage and diabetic retinopathy. This suggests that systemic EGCG administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as RP. The aim of this work was to investigate whether EGCG can protect against RP progression in the animal P23H line 1, the model of RP. Albino P23H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of RP. Pigmented P23H rats were treated via intraperitoneal injection with saline or EGCG at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans rats. Rats treated with EGCG showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23H rats treated with vehicle. EGCG reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase activities. No differences were observed in visual acuity, nitrate levels, nitrite levels or glutathione S-transferase activity. In conclusion, EGCG not only reduced the loss of visual function in P23H rats but also improved the levels of antioxidant enzymes and reduced oxidative damage. This study was approved by the Institutional Animal Care and Use Committee (CEICA) from the University of Zaragoza under project license PI12/14 on July 11, 2014.

Reseña de Marc Vuillermoz, dir., Les idées du Théâtre. Paratextes français, italiens et espagnols del XVIe et XVIIe siècles

En la senda abierta por los trabajos biográficos sobre la intelectual y librepensadora brasileña, Maria Lacerda de Moura, este artículo busca contribuir al estudio de su despliegue intelectual fuera de Brasil. Tiene por marco general investigaciones previas relacionadas con la importancia de las publicaciones periódicas y los proyectos editoriales de las izquierdas en su animación del debate transnacional sobre la denominada “cuestión sexual”. Como objetivo específico, se rastrean y analizan en sus contactos con el anarquismo que se desarrolló en la Argentina en las primeras décadas del siglo XX, a partir de tres momentos específicos: las primeras huellas del nombre de Maria Lacerda en la prensa anarquista, su visita a la Argentina en 1929 y su intercambio con el médico y escritor anarquista, Juan Lazarte. En cuanto al abordaje metodológico, este trabajo abreva en los aportes más recientes del dinámico campo de estudios vinculado a las revistas político-culturales.

This paper highlights the relevance of the structural design of Saving Private Ryan (Steven Spielberg, 1998) in conveying its message, in line with S. M. Eisenstein's theoretical principles. An analysis of its scenes has been carried out, identifying their emulation of, or "collisions" with, preceding "schemas". The film presents events characteristic of the classical model of the World War II combat subgenre, but its articulation is unforeseen and evidences authorial action as in the critical model of Vietnam, specifically as in Apocalypse Now (Francis Ford Coppola, 1979). This contrast integrates citizens of different ideological persuasions. It also borrows the structural model and deceptive ending to a initial enigma from Citizen Kane (Orson Welles, 1941) so as to allude to the same theme: the true essence of man, in this case of the veteran, represented by the elderly Ryan.

As new phage-defense systems (PDs) are discovered, the overlap between their mechanisms and those of toxin/antitoxin systems (TAs) is becoming clear in that both use similar means to reduce cellular metabolism; for example, both systems have members that deplete energetic compounds (e.g., NAD+, ATP) and deplete nucleic acids, and both have members that inflict membrane damage. Moreover, both TAs and PDs are similar in that rather than altruistically killing the host to limit phage propagation (commonly known as abortive infection), both reduce host metabolism since phages propagate less in slow-growing cells, and slow growth facilitates the interaction of multiple phage-defense systems.

The autograph manuscript of El cardenal de Belén contains, among others, the typical marks of the count that were made in the print-shop to estimate the amount of manuscript text corresponding to printed text. This circumstance is anomalous, because this sort of fair copy, except in a few and very rare occasions, was not the author’s autograph manuscript, but rather a clean copy made by a professional. This paper offers an explanation of why the print-shop of Viuda de Alonso Martín had to use, in an exceptional manner, this manuscript. On the way, we also studied some implications related to the editorial process, such as the ascertainment that the dedicatories were not included in this fair copy.

This article analyses the evolution of the paradigm of the antiterrorist strategy and its most recent manifestation in Europe: policies for prevention of violent extremism (PVE). By means of a wide-ranging survey of the literature evaluating the PVE at the European level, the article is concerned with the main political and social consequences of these policies as they are described in the academic literature. By focusing on abstract, ideological elements — extremism — and concentrating on the related ideologies, the result of the PVE is a prevention policy that penetrates and securitises social, domestic, and private spheres, while also incorporating new security-related actors. As will be shown, this logic turns out to be problematic and, in some cases, counterproductive.

Netflix has shaken up audiovisual industry, but what about academic research? This bibliometric analysis focuses on 210 papers indexed in Web of Science that address this issue. We examine the author, university of affiliation, language, journal, keywords, year of publication, citations received, and categories covered in WoS. We also conducted a quantitative analysis of abstracts and papers to identify the most recurrent methodologies, themes, and samples. Our results highlight a rise in Netflix studies in recent years and their tendency to analyse specific audiovisual works. There are many qualitative analysis of specific Netflix hits, but none of the shows particularly stands out. It also shows a rise in “Communication” and “Film, Radio & Television” papers (40% of them), although academic interest relies on Netflix corporate culture, business, and algorithm. These studies are mainly carried out using a qualitative methodology (83%). More than half of the articles focus on one of the Netflix series and, among them, the greatest interest lies in the representation of specific issues; gender, race and sexuality are present in 25% of the works in the sample (n=210). At the same time, among the 367 authors signing these research papers, the parity between men (51%) and women (49%) is almost absolute. It appears that the geographical and linguistic variety of papers is related to Netflix’s global expansion and that the sheer number of titles covered reveals a fleeting attention due to Netflix’s trademark: swift and concentrated consumption.

ABSTRACT At the end of 2019, a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a pandemic that persists to date and has resulted in more than 6.2 million deaths. In the last couple of years, researchers have made great efforts to develop a diagnostic technique that maintains high levels of sensitivity and specificity, since an accurate and early diagnosis is required to minimize the prevalence of SARS-CoV-2 infection. In this context, CRISPR-Cas systems are proposed as promising tools for development as diagnostic techniques due to their high specificity, highlighting that Cas13 endonuclease discriminates single nucleotide changes and displays collateral activity against single-stranded RNA molecules. With the aim of improving the sensitivity of diagnosis, this technology is usually combined with isothermal preamplification reactions (SHERLOCK, DETECTR). Based on this, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP)-CRISPR-Cas13a method for SARS-CoV-2 virus detection in nasopharyngeal samples without using RNA extraction that exhibits 100% specificity and 83% sensitivity, as well as a positive predictive value (PPV) of 100% and negative predictive values (NPVs) of 100%, 81%, 79.1%, and 66.7% for cycle threshold (CT) values of 30 and overall, respectively. IMPORTANCE The coronavirus disease 2019 (COVID-19) crisis has driven the development of innovative molecular diagnosis methods, including CRISPR-Cas technology. In this work, we performed a protocol, working with RNA extraction kit-free samples and using RT-LAMP-CRISPR-Cas13a technology; our results place this method at the forefront of rapid and specific diagnostic methods for COVID-19 due to the high specificity (100%), sensitivity (83%), PPVs (100%), and NPVs (81% for high viral loads) obtained with clinical samples.