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Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events. We found that acPD-1 and CPMV/acPD-1 injections resulted in tumor control and a reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of treated dogs. In two metastatic CMC patients, CPMV/acPD-1 treatments resulted in the control and reduction of established lung metastases. CPMV/acPD-1 treatments were associated with altered gene expression related to TLR1-4 signaling and complement pathways. These novel therapies could be effective for CMC patients. Owing to the extensive similarities between CMC and human BC, IT CPMV combined with approved anti-PD-1 therapies could be a novel and effective immunotherapy to treat local BC and suppress metastatic BC.

Abstract This paper presents a novel method for identifying critical transmission lines (CTLs) in power systems subjected to cascading overload outages, leveraging the Natural Connectivity (NC) index. Unlike previous studies that employed suboptimal weights for the edges, this work introduces a new weighting strategy that enhances the effectiveness of NC in CTLs identification. The proposed Weighted Natural Connectivity-based (WNC-based) method is validated through comparisons with established methods, including the catastrophic expectation index, and the cascading failure simulation index, using IEEE test systems of 30, 39, 57, and 118 buses and the 400 kV Mexican power system. The experimental results demonstrate that the WNC-based method accurately identifies critical lines, providing a practical balance between simplicity and precision. This study challenges prior conclusions that natural connectivity is unsuitable for CTLs identification, showcasing its potential in power system applications. Furthermore, the method's applicability extends to interconnected systems, such as the integration of power transmission, gas distribution, and telecommunication networks, paving the way for future research. The WNC-based method offers a practical tool for preventing blackouts and enhancing power grid resilience, contributing significantly to the field of power system reliability and stability.

Dengue cases rose to record levels during 2023–2024. We investigated dengue in Valle del Cauca, Colombia, to determine if specific virus serotypes or lineages caused its large outbreak. We detected all 4 serotypes and multiple lineages, suggesting that factors such as climatic conditions were likely responsible for increased dengue in Colombia.

Abstract Classifying individuals based on metabotypes and lifestyle phenotypes using exploratory factor analyses, cluster definition, and machine-learning algorithms is promising for precision chronic disease prevention and management. This study analyzed data from the NUTRiMDEA online cohort (baseline: n = 17332 and 62 questions) to develop a clustering tool based on 32 accessible questions using machine-learning strategies. Participants ranged from 18 to over 70 years old, with 64.1% female and 35.5% male. Five clusters were identified, combining metabolic, lifestyle, and personal data: Cluster 1 (“Westernized Millennial”, n = 967) included healthy young individuals with fair lifestyle habits; Cluster 2 (“Healthy”, n = 10616) consisted of healthy adults; Cluster 3 (“Mediterranean Young Adult”, n = 2013) represented healthy young adults with a healthy lifestyle and showed the highest adherence to the Mediterranean diet; Cluster 4 (“Pre-morbid”, n = 600) was characterized by healthy adults with declined mood; Cluster 5 (“Pro-morbid”, n = 312) comprised older individuals (47% >55 years) with poorer lifestyle habits, worse health, and a lower health-related quality of life. A computational algorithm was elicited, which allowed quick cluster assignment based on responses (“lifemetabotypes”). This machine-learning approach facilitates personalized interventions and precision lifestyle recommendations, supporting online methods for targeted health maintenance and chronic disease prevention.

El objetivo de este estudio fue analizar los factores que inciden en el comportamiento de los consumidores paraguayos en relación al comercio electrónico. Se utilizó una metodología cuantitativa, transversal y descriptiva, recolectando datos a través de una encuesta en formato digital realizada a un total de 404 participantes tomados a partir de una muestra aleatoria simple en el 2023. Los resultados demostraron que 48,1% apuntan a la Moda e Indumentaria como el rubro más comprado, 40,6% por Alimentos y Bebidas, 51% compra una vez al mes, 41,4% considera que realizar compras en línea es muy conveniente, 38,3% y 36,5% están de acuerdo o muy de acuerdo en encontrar mejores ofertas en línea, 49,9% expresan su fuerte acuerdo con respecto que la variedad de productos disponibles es altamente valorada, etc. Se concluye que la mayoría de los participantes señala como factores determinantes en la elección de esta modalidad a los tiempos y horarios de atención y también a las opciones de envío y entrega de las mercaderías. Finalmente, existe una constante evolución y aumento en la aceptación de los consumidores de esta modalidad a nivel local.

Abstract The integration of alternative energy sources, storage systems, and modern loads into the distribution grid is complicating its operation and maintenance. Variability in individual generation and consumption elements dynamically affects voltage profiles, which in turn undermines efficiency and power quality. This study proposes to address this dynamical variability using an online reconfiguration approach that involves opening and closing switches to modify the grid's topology and adjust voltage levels in response to load/generation variations. Other grid optimization techniques, based on reconfiguration, typically focus on static, fully instrumented grids with predictable parameters and homogeneous changes, aiming to minimize power losses but overlooking the dynamics of variable grid elements. This study proposes a testing approach that is dependent on the estimated transient status of the grid only using a limited number of measurement units and considering the individual‐stochastic variations of loads and generators. The proposed approach was tested on the IEEE 33‐bus test feeder with up to five varying distributed generators. The results confirm that the algorithm consistently finds a reconfiguration alternative that could enhance system efficiency and voltage profiles, even in the face of dynamic load/generator behavior, demonstrating its effectiveness and online adaptability for grid operation and management tasks.

Abstract Reconstructing the history—such as the place of birth and death—of an individual sample is a fundamental goal in ancient DNA (aDNA) studies. However, knowing the place of death can be particularly challenging when samples come from museum collections with incomplete or erroneous archives. While analyses of human DNA and isotope data can inform us about the ancestry of an individual and provide clues about where the person lived, they cannot specifically trace the place of death. Moreover, while ancient human DNA can be retrieved, a large fraction of the sequenced molecules in ancient DNA studies derive from exogenous DNA. This DNA—which is usually discarded in aDNA analyses—is constituted mostly by microbial DNA from soil-dwelling microorganisms that have colonized the buried remains post-mortem. In this study, we hypothesize that remains of individuals buried in the same or close geographic areas, exposed to similar microbial communities, could harbor more similar metagenomes. We propose to use metagenomic data from ancient samples' shotgun sequencing to locate the place of death of a given individual which can also help to solve cases of sample mislabeling. We used a k-mer-based approach to compute similarity scores between metagenomic samples from different locations and propose a method based on dimensionality reduction and logistic regression to assign a geographical origin to target samples. We apply our method to several public datasets and observe that individual samples from closer geographic locations tend to show higher similarities in their metagenomes compared to those of different origin, allowing good geographical predictions of test samples. Moreover, we observe that the genus Streptomyces commonly infiltrates ancient remains and represents a valuable biomarker to trace the samples' geographic origin. Our results provide a proof of concept and show how metagenomic data can also be used to shed light on the place of origin of ancient samples.

Este artículo presenta una aproximación biográfica a la figura de Catalina Bravo, una actriz relegada al olvido. Recorre su trayectoria artística en los principales teatros madrileños, Príncipe y de la Cruz, y en el Teatre de la Santa Creu de Barcelona, destacando el repertorio que interpretó, su evolución en la jerarquía de actrices y su reflejo retributivo, así como la recepción de su trabajo por la crítica. Recientemente se ha conocido que la actriz interpretó la única intervención musical del drama de Hartzenbusch Los amantes de Teruel. Se pretende, desde esta investigación, recuperar la trayectoria escénica de Catalina Bravo prestando atención a su vertiente musical para poder discernir si la actuación en el drama de Hartzenbusch fue anecdótica o si su repertorio acredita que pueda ser considerada una canta-actriz, de la misma manera que sus coetáneas Matilde Díez o Bárbara Lamadrid.

El objetivo consiste en analizar el uso del papel en la gestión universitaria. Se sustentó en un enfoque cuantitativo, transversal, exploratorio y descriptivo. La población y muestra se compuso por 12 personas que desempeñan funciones dentro de la cadena de mando (directivos, administrativos y académicos) en la Facultad de Ciencias Económicas y Empresariales (FACEM) de la Universidad Nacional de Canindeyú (UNICAN), con sede en Salto Guairá y filial en Curuguaty, Paraguay. Se empleó una encuesta mediante un cuestionario de 19 preguntas, remitido vía WhatsApp por conveniencia en el 2023. Como resultados se muestra que 41,7% indicó que el uso del papel es imprescindible en su labor; 66,7% reconoce el ahorro de recursos económicos disminuyendo o eliminando la utilización del papel; 75% identificó la existencia de una alta dependencia del papel en cumplimiento de sus funciones; y 58,3% determinó que con la disminución de impresiones se realiza ahorro de energía eléctrica. Se concluye que, a pesar de una considerable utilización del papel en las labores rutinarias, se perciben que la implementación de la política de Papel Cero en la FACEM-UNICAN podría generar ahorro en diversos recursos, facilitar la transición a la era digital y contribuir a la preservación del medio ambiente.

Gut microbiota exert functions of high importance in the intestine. Furthermore, there is increasing evidence for its role in immune regulation and maintenance of homeostasis in many physiological processes taking place in distant tissues. In particular, in this review, we explore the impact of metabolites produced by the gut microbiota on the development of atopic dermatitis (AD). Probiotics and prebiotics balance the microbiota and promote the generation of bacterial metabolites, such as short-chain fatty acids and tryptophan derivates, which promote the regulation of the exacerbated AD immune response through regulatory T cells and IL-10 and TGF-β cytokines. Metabolites also have a direct action on keratinocytes once they reach the bloodstream. Besides, probiotics decrease the levels of metabolites associated with AD onset, such as phenols. Understanding all these crosstalk processes between the gut and the skin reveals a number of possibilities, mainly through the manipulation of the gut microbiome, which may represent therapeutic strategies that can contribute to the standard treatments of AD patients to improve their quality of life.

The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV's drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity.

Osteosarcomas of the ribs are rarely reported but have a high potential for pulmonary metastases. The therapeutic strategies for this disease are not well defined. The primary treatment recommendations include wide resection with clear surgical margins and chest wall reconstruction if needed. We present a case of costal osteosarcoma with pleural and lung extension successfully treated by en-bloc thoracic resection with free surgical margins and chest wall reconstruction with rib titanium bars, polypropylene mesh and a rectus abdominis free flap with microvascular anastomoses. This case demonstrates the importance of this therapeutic strategy and highlights the need of early intervention in managing this disease.

ABSTRACT First isolated from neotropical fruit bats in Trinidad in 1956, Tacaribe virus (TCRV) has rarely been detected since. We searched for New World arenavirus reads in roughly 5.7 million sequencing runs available on public databases using Serratus. We recovered a complete genome of a divergent TCRV in metatranscriptomic data derived from heart and eye tissue of an adult male Jamaican fruit-eating bat sampled in the Dominican Republic, 2014. In total, 2,733 reads were mapped resulting in mean coverages of 7.4-fold for the L and 10.2-fold for the S segment. Re-testing original bat specimens showed the highest viral loads in liver tissue (245 copies/mg). Sanger sequencing of PCR amplicons from liver confirmed correctness of and completed the genome recovered from metatranscriptomic data, revealing conserved arenavirus genomic organization, length, intergenic regions, and genome termini. The newly found TCRV strain tentatively named DOM2014 clustered in a basal sister relationship to all other known TCRV strains with which it shared between 83.3%–86.0% genomic and 91.8%–93.7% translated amino acid sequence identity across protein-coding regions. DOM2014 showed a conserved glycine, proline, proline, threonine (GPPT) nucleoprotein motif, which is essential for TCRV interferon β antagonism. Our data confirm the association of TCRV with the bat genus Artibeus put into question by lethal experimental infections and scarce bat-derived TCRV genomic data. Broad genetic diversity and geographic spread require assessments of TCRV strain-associated pathogenicity, particularly for DOM2014 as a highly divergent TCRV strain. Confirmation of genomic database findings by testing original specimens provides robustness to our findings and supports the usefulness of metatranscriptomic studies.IMPORTANCEClade B New World arenaviruses (NWA) include rodent-borne lethal hemorrhagic fever viruses, whereas Tacaribe virus (TCRV) stands out because of its detection in bats and its presumably low zoonotic potential. However, the bat association of TCRV was put into question by lethal experimental neotropical fruit bat infections and rare TCRV detection in bats. Scarce genomic data include near-identical viruses from Caribbean bats and ticks from the US sampled 50 years later. The prototype TCRV isolate used for experimental risk assessments has an extensive passage history in suckling mouse brains. Exploring the true genetic diversity, geographic distribution, and host range of bat-borne NWA is pivotal to assess their zoonotic potential and transmission cycles. We analyzed metatranscriptomic data for evidence of NWA identifying a highly divergent TCRV in bats and confirmed virus detection in original biological materials, supporting the association of TCRV with neotropical bats and warranting investigation of strain-associated TCRV pathogenicity.

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We found that although mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly long interspersed elements, drive increases in genome size, whereas DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TEs at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals.

Abstract Fomes weberianus Bres. & Henn. ex Sacc. is currently the basionym of two very distinct polypores (Basidiomycota), Ganoderma weberianum (Polyporales) and Phylloporia weberiana (Hymenochaetales). This fact has led to almost fifty years of taxonomic confusion. Fomes weberianus was first lectotypified by Steyaert, who accepted the species as G. weberianum. However, studies of Weber’s original material in B, duplicate material in S, the protologue, and early interpretations of the name have shown that Steyaert’s choice conflicts with the protologue and early interpretations, and that his interpretation as a species of Ganoderma is erroneous. A new lectotype was designated and the species was re-described under the correct interpretation Phylloporia weberiana.

El objetivo del estudio consistió en la obtención de indicadores de violencia y prácticas escolares de discriminación y normalización en población universitaria, como sustento para la construcción de un instrumento psicométrico que permita obtener información para la toma de decisiones en materia de prevención e intervención de la violencia escolar. La investigación es cuantitativa y corresponde a un estudio instrumental, mediante un diseño de dos fases: exploración de indicadores y de validez de construcción. La población participante fue seleccionada a través de un muestreo no probabilístico de tipo intencional. En la primera fase, participaron 30 personas de los cursos de formación ciudadana y formación en valores. En la segunda fase, fue seleccionado, mediante un muestreo no probabilístico de tipo intencional, un grupo de 502 participantes inscritos en el nivel medio superior y nivel superior de una universidad pública. La primera fase pretendió explorar indicadores de prácticas y disposiciones de discriminación y normalización con respecto a la violencia, mediante un cuestionario de opinión. Se seleccionaron las diez respuestas más representativas de cada categoría, con sustento en la información recabada por dicho cuestionario se diseñó un instrumento. En la segunda fase, se procedió a la obtención de evidencias de validez referidas a la estructura interna y confiabilidad/precisión del instrumento diseñado, mediante las técnicas estadísticas de análisis factorial exploratorio de rotación varimax de componentes principales y el alfa de Cronbach. Los resultados reportan una varianza acumulada de 50.695 %, explicada por cuatro factores denominados con sustento en el contenido de la agrupación de los reactivos: factor uno Prácticas escolares de acoso y violencia, comprende cinco indicadores; el factor dos explora las prácticas escolares de tolerancia de la violencia a través de cuatro reactivos; el tercer factor comprende las disposiciones personales a la discriminación de género, mediante cuatro reactivos y el factor cuatro explora, mediante tres reactivos, las prácticas personales de normalización de la violencia. El análisis de consistencia interna reportó un alfa de Cronbach .807. El instrumento reportó evidencias de validez referidas al constructo y de confiabilidad/ precisión. La estructura factorial es congruente con indicadores de antivalores que se configuran como prácticas de anticultura.

Introduction: Management in healthcare organizations enables the competitive performance of healthcare institutions; therefore, it requires constant monitoring with valid and reliable instruments. Objective: To validate a scale to evaluate management in health care organizations, according to the perception of health care workers. Methods: Instrumental study, in which 302 health workers from hospitals and primary care centers in a health region of Peru participated. The process included content validation by expert judgment and pilot testing. construct validity was assessed by exploratory factor analysis and fit was assessed by confirmatory factor analysis, which included different estimation methods. Discriminant, predictive and reliability validity were analyzed. Results: A short version of 8 items grouped in a single general factor was obtained, which explained 55.88% of the total variance; the model has adequate goodness-of-fit indices independently of the estimation method used. The variability indexes of the items were excellent; the discriminative and predictive validity were satisfactory. The internal consistency with McDonald's omega (ω= 0.892), Cronbach's alpha (α= 0.892) and Gutmann (λ6= 0.887), revealed optimal reliability values. Conclusions: The scale for evaluating management in healthcare organizations has adequate metric properties.