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Abstract During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

Abstract Biodiversity loss is extreme in amphibians. Despite ongoing conservation action, it is difficult to determine where we stand in overcoming their extinction crisis. Among the most threatened amphibians are the 131 Neotropical harlequin toads. Many of them declined since the 1980s with several considered possibly extinct. Recently, more than 30 species have been rediscovered, raising hope for a reversing trend in the amphibian extinction crisis. We use past and present data available for harlequin toads (Atelopus), to examine whether the amphibian extinction crisis is still in an emergency state. Since 2004 no species has improved its population status, suggesting that recovery efforts have not been successful. Threats include habitat change, pathogen spread and climate change. More mitigation strategies need implementation, especially habitat protection and disease management, combined with captive conservation breeding. With harlequin toads serving as a model, it is clear that the amphibian extinction crisis is still underway.

The biomedical research process must follow certain quality criteria in its design and development to ensure that the results are credible and reliable. Once completed, the time comes to write an article for publication. The article must present in sufficient detail, and in a clear and transparent manner, all the information on the research work that has been carried out. In this way, readers, after a critical reading of the published content, will be able to judge the validity and relevance of the study and, if they so wish, make use of the findings.In order to improve the description of the research process for publication, a series of guidelines have been developed which, in a simple and structured way, guide authors in the preparation of a manuscript. They are presented in the form of a list, flowchart, or structured text, and are an invaluable aid when writing an article.This article presents the reporting guidelines for the most common designs along with the corresponding checklists. Resumen: El proceso de investigación biomédica debe seguir unos criterios de calidad en su diseño y elaboración, que garanticen que los resultados son creíbles y fiables. Una vez finalizado, llega el momento de escribir un artículo para su publicación. Este debe presentar con suficiente detalle, y de forma clara y transparente, toda la información del trabajo de investigación realizado. De esta forma, los lectores, tras una lectura crítica de lo publicado, podrán juzgar la validez y la relevancia del estudio, y si lo consideran, utilizar los hallazgos.Con el objetivo de mejorar la descripción del proceso de investigación para su publicación, se han desarrollado una serie de guías que, de forma sencilla y estructurada, orientan a los autores a la hora de elaborar un manuscrito. Se presentan en forma de lista, diagrama de flujo, o texto estructurado, y son una ayuda inestimable a la hora de escribir un artículo.Este artículo presenta las guías de elaboración de manuscritos de los diseños más habituales, con sus listas de verificación.

Resumen: Introducción: Las metástasis vertebrales son un problema muy frecuente y asocian un deterioro importante de la calidad de vida en los pacientes oncológicos. El objetivo de esta revisión es determinar el encaje de las técnicas quirúrgicas mínimamente invasivas dentro del manejo de esta entidad. Métodos: Se realizó una revisión bibliográfica en las bases de datos Google Scholar, PubMed, Scopus y Cochrane. Se revisaron los artículos publicados en los últimos 10 años que fueran de una relevancia y calidad adecuadas. Resultados: Tras el cribado de los 2.184 trabajos identificados inicialmente en las distintas bases de datos, se incluyeron un total de 24 artículos en esta revisión. Conclusión: La cirugía mínimamente invasiva de columna es especialmente útil en pacientes oncológicos frágiles con metástasis vertebrales por la reducida comorbilidad que presentan las técnicas que se engloban en ella en comparación con la de la cirugía abierta convencional. Los avances en tecnología aplicada a la cirugía, como la navegación y la robótica, mejoran la precisión y reducen las complicaciones de esta técnica. Abstract: Background: Spinal metastases are a very common problem which dramatically affects the quality of life of cancer patients. The objective of this review is to address the issue of how minimally invasive surgery can play an important role in treating this pathology. Methods: A literature review was performed, searching in the Google Scholar, PubMed, Scopus and Cochrane databases. Relevant and quality papers published within the last 10 years were included in the review. Results: After screening the 2184 initially identified registers, a total of 24 articles were included for review. Conclusion: Minimally invasive spine surgery is specially convenient for fragile cancer patients with spinal metastases, because of its reduced comorbidity compared to conventional open surgery. Technological advances in surgery, such as navigation and robotics, improve accuracy and safety in this technique.

Resumen: Las metástasis espinales representan una importante carga sobre la calidad de vida en los pacientes afectados por una enfermedad oncológica activa, debido a la alta incidencia de síndromes dolorosos, deformidad espinal y deterioro neurológico. La cirugía juega un papel determinante a la hora de mejorar la calidad de vida mediante el control del dolor, el restablecimiento de la función neurológica y el mantenimiento de la estabilidad espinal, además de contribuir a la respuesta de la terapia médica. La cirugía mínimamente invasiva (MIS) es una opción de tratamiento en determinados pacientes con alto riesgo quirúrgico, ya que tiene una baja tasa de complicaciones, de sangrado intraoperatorio, de estancia hospitalaria y ofrece resultados similares a la cirugía abierta.Presentamos en esta revisión el papel de la MIS en esta enfermedad, y algunos casos tratados en nuestro centro hospitalario. Abstract: Spinal metastases represent a significant burden on the quality of life in patients affected by active oncological disease due to the high incidence of pain syndromes, spinal deformity, and neurological impairment. Surgery plays a decisive role in improving quality of life by controlling pain, restoring neurological function and maintaining spinal stability, as well as contributing to the response to medical therapy. Minimally invasive surgery (MIS) is a treatment option in certain patients with high surgical risk since it has a low rate of complications, intraoperative bleeding, hospital stay, and offers similar results to open surgery.In this review, we present the role of MIS in this pathology and some cases treated in our hospital.

Abstract Food dehydration is a preservation technique that guarantees its supply. Food like vegetables and fruits are traditionally dehydrated with natural gas or solar energy, however, this work demonstrates the feasibility of doing it with energy from a geothermal power plant in Nayarit, Mexico. Different species of pineapple (Miel, Cayenne, and Esmeralda) were dehydrated at different temperatures from 64 to 80°C and the safety of the product was subsequently verified, for these aerobic mesophiles (

Abstract The relative importance or saliency of sensory inputs depend on the animal’s environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli. Our study suggests the existence of a form of long-term memory that may modulate the level of neuronal adaptation according to its behavioural relevance, and sets the ground for future experiments that will help to disentangle the functional mechanisms that govern behavioural habituation and its relation to neuronal adaptation.

Androgenetic alopecia, the most common cause of hair loss affecting both men and women, is typically treated using pharmaceutical options, such as minoxidil and finasteride. While these medications work for many individuals, they are not suitable options for all. To date, the only non-pharmaceutical option that the United States Food and Drug Administration has cleared as a treatment for androgenetic alopecia is low-level laser therapy (LLLT). Numerous clinical trials utilizing LLLT devices of various types are available. However, a myriad of other physical treatments for this form of hair loss have been reported in the literature. This review evaluated the effectiveness of microneedling, pulsed electromagnetic field (PEMF) therapy, low-level laser therapy (LLLT), fractional laser therapy, and nonablative laser therapy for the treatment of androgenetic alopecia (AGA). It also explores the potential of multimodal treatments combining these physical therapies. The majority of evidence in the literature supports LLLT as a physical therapy for androgenetic alopecia. However, other physical treatments, such as nonablative laser treatments, and multimodal approaches, such as PEMF-LLLT, seem to have the potential to be equally or more promising and merit further exploration.

Background: File fracture during root canal treatment in endodontics is a major concern for clinicians. The strength of the file is strongly dependent on its geometry, material, and working conditions; finite element simulations are used to understand these failure mechanisms. One limitation of the models used for these simulations is the approximate geometric representation typically obtained by rotating and scaling a specific cross-section shape along the file length. Given the influence of file geometry on file strength, a more realistic representation based on the manufacturing method is needed. Methods: A computerized method was developed to generate the file geometry by simulating the flute grinding manufacturing process. This method generates the 3D geometry of the file starting from a blank and reproducing the motions of the file and grinding wheel. Results: The cross-section of the resulting geometry does not involve simple rotation and scaling but changes from the shank to the tip. The tilt angle of the grinding wheel affects the final geometry, thus altering the convexity of the cross-section. Several other parameters, such as the pitch and the radius of the grinding disc tip, impact the final geometry. Conclusions: The proposed computational method allows for the generation of endodontic file geometries that match those produced via the actual flute grinding method. This tool may help researchers and tool designers in the preparation of finite element models to assess the strength of realistic files.

Accurately characterizing permanent deformation in granular materials subjected to cyclic loading is crucial for pavement design. This paper introduces an alternative approach to characterizing permanent deformation in a framework that reduces the number of load cycle repetitions by applying an alternative analytical strategy based on plastic strain rate variation over time. The methodology uses a cycle-hardening approach to establish correlations between short-term (post-compaction) and long-term (shakedown state) plastic strain accumulation. This alternative approach provides an efficient means to accelerate the characterization of permanent deformation, ensuring the integrity and validity of the assessment in a more time-efficient and resource-optimized way.

Background: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. Methods: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. Results: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): −45–15 min (n = 136; 17.5%, 175.9 ± 271.0); −15–0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). Conclusion: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.

In this study, the authors analyzed the relationship between emotions and the construction of identities, particularly national identity. We reviewed the current debate on the role of emotions and feelings in people's actions and in the configuration of their worldviews and practical actions. The world is witnessing a revival of ideologies that seemed to have been definitively banished from human thought and political action in the 20th century; however, it is being proved not only that they have survived and grown, but that they are also widely disseminated through networks and have come to shape the thinking of the many people who use them when deciding the future of their societies and how they want them to be governed. The growth of populism is based on emotions and on the most extremely nationalistic discourses. We analyzed, first of all, the influence of emotions on the perception of social reality and on the construction of historical and social knowledge. Next, we focused on the implications that emotions have had on the teaching of history and on the results of an international exploratory selection of particularly relevant research. Finally, as a conclusion, we suggest some ideas for the search of a balance that considers the weight of reason and emotion in the teaching and learning of history.

The study investigated the joint contribution of the self-regulated learning (SRL) and individual differences approaches to the prediction of university students' grade point average (GPA) obtained at three separate time points throughout their degree (3 years). We assessed cognitive (i.e., previous academic performance, cognitive ability, and cognitive SRL strategies) and non-cognitive variables (i.e., personality, trait emotional intelligence, motivation, and non-cognitive SRL strategies) in a sample of Spanish undergraduates. Results showed that GPA correlated with previous academic performance (i.e., combination of high school's GPA and college admission test score), academic self-efficacy, academic engagement, SRL strategies, and conscientiousness. Hierarchical regression analyses indicated that non-cognitive factors (i.e., academic engagement, academic self-efficacy, regulation of behavior and context, and conscientiousness) alone explained 17-25% of the variance in GPA across three years, and previous academic performance accounted up to an additional 25% of the variance, jointly reaching an explained variance of up to 50% in GPA. Specifically, academic engagement and regulation of behavior and context demonstrated incremental validity over and above cognitive predictors such as previous academic performance, inductive reasoning and regulation of cognition and metacognition. The role of intelligence, whether cognitive or emotional, was not as obvious as a predictor. Two nested structural equation models explained about 27-29% of the variance in a latent GPA factor exclusively from a proxy of a global variable of non-cognitive factors as a latent predictor, which is a novel and promising proof of its robust criterion validity. Implications and recommendations for future studies are discussed.

Los conocimientos matemáticos se fundamentan y amplían a partir de los conceptos y de sus relaciones con diversas situaciones de la vida práctica; de ahí, la pertinencia de aprovechar las potencialidades de su tratamiento didáctico para la formación integral de los estudiantes desde el proceso de enseñanza-aprendizaje de la Matemática. En consecuencia, el proceso de formación de conceptos se reconoce como una vía fundamental para el desarrollo del pensamiento y, a al análisis de este, se le concede especial importancia en la Didáctica de la Matemática. Es por ello que, este artículo tiene como objetivo exponer los fundamentos, las regularidades didácticas y las exigencias actuales a considerar durante el proceso de formación de conceptos matemáticos. Para su realización se utilizaron métodos teóricos y empíricos; de los primeros se usaron: el histórico-lógico, el analítico-sintético y el inductivo-deductivo, con el fin de hacer generalizaciones en torno a la temática y de los segundos: el análisis documental, para interpretar las aspiraciones y exigencias metodológicas de los documentos rectores vigentes. Su principal resultado lo constituyen las ideas teóricas y metodológicas que se derivaron de la revisión bibliográfica realizada, las cuáles deben guiar el proceso de formación de conceptos matemáticos en la práctica pedagógica.

Summary: The neural mechanisms underlying novelty detection are not well understood, especially in relation to behavior. Here, we present single-unit responses from the primary auditory cortex (A1) from two monkeys trained to detect deviant tones amid repetitive ones. Results show that monkeys can detect deviant sounds, and there is a strong correlation between late neuronal responses (250–350 ms after deviant onset) and the monkeys’ perceptual decisions. The magnitude and timing of both neuronal and behavioral responses are increased by larger frequency differences between the deviant and standard tones and by increasing the number of standard tones preceding the deviant. This suggests that A1 neurons encode novelty detection in behaving monkeys, influenced by stimulus relevance and expectations. This study provides evidence supporting aspects of predictive coding in the sensory cortex.

Se analizó el crecimiento relativo de langosta espinosa Panulirus gracilis, con un enfoque de selección multimodelo y la teoría de la información de Akaike. Se realizaron muestreos en capturas comerciales de langosta espinosa del sur de Sinaloa, México entre las temporadas de pesca de 2014 y 2015 y, 2017 y 2018. En 298 hembras de P. gracilis se registró la longitud cefalotórax (LC) mm, peso total (PT) g y fase de madurez gonádica. La estructura de tallas varió de 54.6 a 103.1 mm de LC. Se observaron hembras maduras a partir de 57.5 mm de LC, con un incremento de proporción de madurez en tallas mayores. El mejor modelo fue Línea Rota (Wi=65.09%) y Dos Segmentos (Wi%=34.87). El cambio en el crecimiento relativo a la talla en ambos modelos, coincidió con un incremento en la proporción de madurez en tallas mayores a 60 mm de LC en P. gracilis.

Abstract Objective This study aimed to describe the performance of a next‐generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. Materials and Methods A cross‐sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021–March 2022) where molecular diagnostic of 537 Formalin‐Fixed Paraffin‐Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). Results AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non‐smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. Conclusion This is the largest cohort‐level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.

La irremediable conexión existente entre la Inteligencia Artificial con el ámbito sanitario provoca que se planteen cuestiones éticas cruciales que requieren un examen con profundidad y una reinterpretación de los valores éticos vigentes hasta hoy en día. Sobre esta base la Filosofía del Derecho se preocupa por defender que la equidad y la justicia sean dogma de fe. Estas situaciones controvertidas se ven reflejadas también en el campo de la sanidad, ya que presentan diferentes materias a resolver sobre la aplicación de la Inteligencia Artificial en el ámbito sanitario desde la perspectiva de la Filosofía del Derecho, tema que va a centrar el núcleo de la investigación de este trabajo. Al respecto aseverar que la Inteligencia Artificial ha tenido un impacto significativo en el campo de la sanidad y la atención sanitaria en diversas áreas de la medicina, pero al mismo tiempo plantea importantes cuestiones éticas que deben ser consideradas cuidadosamente para su adecuada aplicación. En definitiva, la introducción de la Inteligencia Artificial con una reflexión filosófico jurídica plantea numerosos desafíos y suficientes razones para trazar una ruta de análisis sobre la naturaleza del derecho, la ética, la justicia y la responsabilidad de los profesionales en el ámbito sanitario. Los filósofos del derecho están explorando activamente estas cuestiones a medida que la Inteligencia Artificial continúa transformando la forma en que interactúa el sistema legal con los avances tecnológicos desde una perspectiva ética.

ABSTRACT Biological nitrogen fixation, the conversion of inert N2 to metabolically tractable NH3, is only performed by certain microorganisms called diazotrophs and is catalyzed by the nitrogenases. A [7Fe-9S-C-Mo-R-homocitrate]-cofactor, designated FeMo-co, provides the catalytic site for N2 reduction in the Mo-dependent nitrogenase. Thus, achieving FeMo-co formation in model eukaryotic organisms, such as Saccharomyces cerevisiae, represents an important milestone toward endowing them with a capacity for Mo-dependent biological nitrogen fixation. A central player in FeMo-co assembly is the scaffold protein NifEN upon which processing of NifB-co, an [8Fe-9S-C] precursor produced by NifB, occurs. Prior work established that NifB-co can be produced in S. cerevisiae mitochondria. In the present work, a library of nifEN genes from diverse diazotrophs was expressed in S. cerevisiae, targeted to mitochondria, and surveyed for their ability to produce soluble NifEN protein complexes. Many such NifEN variants supported FeMo-co formation when heterologously produced in the diazotroph A. vinelandii. However, only three of them accumulated in soluble forms in mitochondria of aerobically cultured S. cerevisiae. Of these, two variants were active in the in vitro FeMo-co synthesis assay. NifEN, NifB, and NifH proteins from different species, all of them produced in and purified from S. cerevisiae mitochondria, were combined to establish successful FeMo-co biosynthetic pathways. These findings demonstrate that combining diverse interspecies nitrogenase FeMo-co assembly components could be an effective and, perhaps, the only approach to achieve and optimize nitrogen fixation in a eukaryotic organism.IMPORTANCEBiological nitrogen fixation, the conversion of inert N2 to metabolically usable NH3, is a process exclusive to diazotrophic microorganisms and relies on the activity of nitrogenases. The assembly of the nitrogenase [7Fe-9S-C-Mo-R-homocitrate]-cofactor (FeMo-co) in a eukaryotic cell is a pivotal milestone that will pave the way to engineer cereals with nitrogen fixing capabilities and therefore independent of nitrogen fertilizers. In this study, we identified NifEN protein complexes that were functional in the model eukaryotic organism Saccharomyces cerevisiae. NifEN is an essential component of the FeMo-co biosynthesis pathway. Furthermore, the FeMo-co biosynthetic pathway was recapitulated in vitro using only proteins expressed in S. cerevisiae. FeMo-co biosynthesis was achieved by combining nitrogenase FeMo-co assembly components from different species, a promising strategy to engineer nitrogen fixation in eukaryotic organisms.