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AimsWidespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The resulting immune dysregulation of the GI mucosa is believed to predispose patients to viral infections. We characterised the histopathological features of ICIGI and the frequency of viral infections such as cytomegalovirus (CMV), adenovirus, and Epstein-Barr virus (EBV).MethodsSingle-centre retrospective study (2011-2020).Results81 GI biopsies from 31 patients with ICIGI (65% male (20/31), 35% female (11/31)) with advanced malignancies were reviewed. Most patients received ipilimumab and nivolumab (14/31, 45%), followed by pembrolizumab (9/31, 29%), ipilimumab (4/31, 13%), nivolumab (2/31, 6%) and combination of all three medications (2/31, 6%). Average regimen prior to incidence of diarrhea was three cycles. Evidence of colitis or erythema by endoscopy was present in 77% of cases, while 23% showed normal endoscopy. Histologically, the predominant ICIGI findings were active inflammation (84%), including cryptitis (77%), crypt abscesses (65%), lymphocytic colitis-like (LCL) pattern (61%), increase in epithelial apoptosis (74%) and/or surface injury (81%). Only one case showed diffuse CMV positivity (3%) with characteristic CMV viral cytopathic effects present on H&E stain and four cases were positive for rare EBV (13%). Adenovirus infection was not identified.ConclusionWhile our cohort is small, ICIGI generally demonstrates active inflammation including cryptitis and crypt abscesses in the colon, LCL pattern, and an increase in epithelial apoptosis. Upfront immunohistochemistry for viral infection without high-degree of clinical and histologic suspicion is not recommended.

En este trabajo pretendemos mostrar que la influyente tesis historiográfica de la “filosofía como forma de vida” de Pierre Hadot según la cual, el sello distintivo de la filosofía antigua fue la consistencia entre vida y doctrina, no es una tesis empírica rastreable históricamente, sino un ejemplar más de la denominada “falacia normativista” a través de la cual Hadot proyectó su concepción de la filosofía proveniente del monacato católico y del existencialismo. Consideramos que sin este importante apoyo el ideal mismo de consistencia entre vida y doctrina pierde una de sus principales bazas. Finalmente, y apelando a evidencia empírica reciente, mostramos que dicho ideal tampoco se concretiza en nuestros días.

Summary: Background: The proportion of people living with HIV (PLWHIV) co-infected with HCV in Mexico was unknown. Our aim was to estimate the seroprevalence of HCV among adults with HIV in Mexico. Methods: Using a complex-survey design, we collected blood samples and applied structured questionnaires between May 2nd, 2019 and February 17th, 2020 in a nationally, representative sample of adults receiving care for HIV-infection in 24 randomly selected HIV-care centres in 8 socio-demographically regions in Mexico. We tested serum for anti-HCV IgG antibodies and collected data on risky exposures. We estimated the seroprevalence of HCV and associated exposures using regression models and the Taylor linearization method to account for the cluster effect by region and centre. Findings: We collected blood samples of 2545 participants. Most participants were men (75.8%) with a median age of 37 years. The estimated seroprevalence of HCV is 3.9% (95% CI 3.1%–4.7%). Only 39 of 99 participants (40%) with HCV antibodies had active replication determined by RNA quantification. Seroprevalence of HCV was significantly higher among people with life-time history of imprisonment (9%, 95% CI 4.4%–13.6%), tattoo use (5.9%, 95% CI 3.9%–8%), and lifetime (22.3%, 95% CI 12.1%–32.6%) and recent (49.3%, 95% CI 18.3%–80.3%) injecting-drug use. Interpretation: Seroprevalence of HCV infection among PLWHIV in Mexico is ten times as high as the seroprevalence for the general population. The national program for HCV elimination focused in PLWHIV should target people that use injecting drugs and living in prisons. Funding: Abbvie Farmacéuticos, S.A de C.V Mexico through Investigator Initiated Study (2018).

Resumen: El envejecimiento de la población es un fenómeno global que está aumentando la proporción de las personas mayores, especialmente aquellas de más de 80 años. Este incremento en la longevidad no siempre se traduce en años de buena calidad de vida. Este documento evalúa la evidencia más reciente sobre las principales actividades preventivas en las personas mayores, comenzando por los grandes síndromes geriátricos como la fragilidad, el deterioro cognitivo y el aislamiento social. Se analizan intervenciones directas en nutrición, deprescripción y ejercicio físico. Además, por primera vez, se incluye un análisis de actividades preventivas en relación con el suicidio en las personas mayores, coordinado con programas de salud mental. La fragilidad, definida como el deterioro progresivo de los sistemas fisiológicos, es un predictor significativo de eventos adversos de salud y se considera potencialmente reversible, especialmente en sus fases tempranas. El diagnóstico y manejo de la fragilidad mediante una valoración geriátrica integral (VGI) y la implementación de intervenciones específicas como el ejercicio multicomponente, la nutrición adecuada y la revisión de medicamentos, son clave para mejorar la funcionalidad y calidad de vida de las personas mayores. Abstract: Population aging is a global phenomenon that is increasing the proportion of older people, particularly those over 80 years old. This increase in longevity does not always translate into years of good quality of life. This document reviews the latest evidence on the main preventive activities for older adults, starting with major geriatric syndromes such as frailty, cognitive impairment, and social isolation. It evaluates direct interventions in nutrition, deprescription, and physical exercise. Additionally, for the first time, it includes an analysis of preventive activities related to suicide in older adults, coordinated with mental health promotion programs. Frailty, defined as the progressive deterioration of physiological systems, is a significant predictor of adverse health events and is considered potentially reversible, especially in its early stages. The diagnosis and management of frailty through comprehensive geriatric assessment (CGA) and the implementation of specific interventions such as multicomponent exercise, adequate nutrition, and medication review are key to improving the functionality and quality of life of older adults.

Esta propuesta de hermenéutica arquitectónica se formula por un grupo de investigadores de distintas áreas de conocimiento. Nuestro objetivo es enriquecer la investigación y la docencia de la Arquitectura, enfocándonos en la producción de los últimos 30 años en un contexto internacional. Se trata de un modo de trabajo colectivo y transversal que permite, profundizando en casos concretos, encontrar modos de hacer que permitan entender iterativamente sectores crecientes, de arquitectura reciente y de arquitectura precedente. Nuestro grupo evoluciona enfocándonos en objetivos a medio plazo que nos permitirán mejorar nuestra interacción docente e investigadora. Exponemos uno de los casos, una obra del estudio OMA, el BLOX (Copenhague, 2006-2018). En este ejemplo se pone de manifiesto la utilidad de la metodología escogida para desvelar aspectos del edificio que no aparecen en las reseñas bibliográficas disponibles hasta la fecha. Las fases propuestas en la interpretación —descripción, genealogía-teratología, y significado— se han visto enriquecidas por las aportaciones transversales de los componentes del grupo. Así se han identificado cuestiones subyacentes en la obra que articulan tanto el entretejido de funciones, como la descomposición volumétrica del edificio. Estas claves están también presentes en muchos edificios contemporáneos construidos con volúmenes complejos que desafían la estática tradicional de la Arquitectura. El estudio del BLOX nos facilita el conocimiento sobre cómo esta técnica tiene resultados formales muy diversos y abre la comprensión de la producción arquitectónica contemporánea, a medida que se complementa con el estudio sucesivo de más obras.

Introducción: El Corte Inglés (ECI) anunció el 12 de marzo de 2022 el cierre de edificios dedicados al retail y el despido de 3000 trabajadores. Los informes financieros resaltaron la crisis financiera debida a la pandemia de la COVID-19, la competencia de minoristas, el incremento de costes de alquiler y salarios, el aumento de los costes de importación por la devaluación del euro, el incremento de la deuda por expansión empresarial, la falta de inversión en tecnología y los cambios en los patrones de consumo. Objetivo: ¿cuáles son las razones que provocaron el fracaso de El Corte Inglés al no ser capaz de anticipar el auge del comercio electrónico?, ¿cómo se enfrentó al reto de los cambios tecnológicos?, ¿cómo se adaptó a las nuevas propuestas de valor que les ofrecían a sus clientes? Metodología: se aplica el método de investigación cualitativo de opinión, que incluye variables como las barreras de implantación de la tecnología, el talento competitivo de los consejos de administración y la innovación en la cultura de la empresa. Resultados: El Corte Inglés nos muestra cómo la falta de adaptación al comercio electrónico llevó a una crisis de marca. La dirección prefirió mantener la cultura empresarial original, que priorizaba la estabilidad sobre la innovación y la adaptación al medio. Esta resistencia al cambio y el enfoque de preservar estructuras jerárquicas obstaculizó la innovación y la respuesta al mercado, lo que evidenció un conflicto entre la cultura establecida y la necesidad de adaptación estratégica, impulsada solo por presiones financieras. Limitación: destaca la dificultad de acceso a las personas clave de la organización debido a su cultura organizativa, la cual valora mucho la discreción. Se planeó un estudio de caso con entrevistas a directivos, pero los obstáculos llevaron a optar por una metodología cualitativa de opinión. Contribución: la contribución y la originalidad de este estudio residen en abordar un vacío académico, dado que hay una escasez de investigaciones que examinen las crisis derivadas de la falta de previsión en el sector del comercio electrónico. Este análisis, al considerar la importancia de la empresa estudiada, nos permite desarrollar un modelo analítico que puede ser utilizado en futuras investigaciones. Además, se abordan las barreras al cambio tecnológico y la adaptación al entorno, lo que proporciona una comprensión integral de estos desafíos.

Introduction: Values are crucial in decision-making, including processes related to science and technology, despite scientists often being unaware of them. Because a goal of science, technology, engineering, and mathematics (STEM) is to foster innovation, values have become fundamental in directing science and technology policies and shaping organizational cultures to leverage innovation. However, most research on STEM education has focused on improving performance or access to STEM education while overlooking its axiological configuration. This study analyzes the different value systems emerging in the current literature on STEM higher education and identifies the relevant stakeholders. Method: In this systematic review and ethical meta-analysis, we aimed to assess the most prominent studies on STEM education and its core values. We followed a Ricoeur-inspired hermeneutical methodology using Atlas ti 8.4.4. Values are identified and classified using a systematic approach to integrate axiological landscapes. Results: The literature does not explicitly discuss the value of STEM education for innovation. However, social values appear to be at the intersection and the cornerstone of basic, economic, aesthetic, and epistemic values, as most social values also manifest these four systems. The most common manifestation of the value system is the capability approach to justice, followed by the beauty of recognition and success and, in third place, racism and social disparities. The analyzed literature emphasizes STEM education's social, political, and economic determinants. However, there is an epistemic gap in the indispensable value of innovating and assessing STEM education. Conclusions: We propose an organizational culture model for STEM education that considers the goals, ends, values, and behaviors of students, teachers, educational institutions, and the government. This model can help fill the axiological gaps in STEM education.

Abstract The intestinal lumen is filled with diverse chemical and physical stimuli. Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function. Yet, the neuro-epithelial connections remain poorly resolved, in part because the tools for orchestrating interactions between these cellular compartments are lacking. We describe the development of a two-compartment microfluidic device for co-culturing enteric neurons with intestinal epithelial cells. The device contains epithelial and neuronal compartments connected by microgrooves. The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids. We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week. In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons (IPANs) from transgenic mice that expressed the fluorescent protein tdTomato. IPANs extended projections into microgrooves, surrounded and frequently made contacts with epithelial cells. The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment. Our microfluidic device represents a platform that may, in the future, be used to dissect structure and function of neuro-epithelial connections in the gut and other organs (skin, lung, bladder, and others) in health and disease.

Determining the sources of water provisioning streams, soils, and vegetation can provide important insights into the water that sustains critical ecosystem functions now and how those functions may be expected to respond given projected changes in the global hydrologic cycle. We developed multi-year time series of water isotope ratios (δ18O and δ2H) based on twice-monthly collections of precipitation, lysimeter, and tree branch xylem waters from a seasonally dry tropical montane cloud forest in the southeastern Andes mountains of Peru. We then used this information to determine indices of the seasonal origins, the young water fractions (Fyw), and the new water fractions (Fnew) of soil, stream, and tree water. There was no evidence for intra-annual variation in the seasonal origins of stream water and lysimeter water from 1 m depth, both of which were predominantly comprised of wet-season precipitation even during the dry seasons. However, branch xylem waters demonstrated an intra-annual shift in seasonal origin: xylem waters were comprised of wet-season precipitation during the wet season and dry-season precipitation during the dry season. The young water fractions of lysimeter (< 15 %) and stream (5 %) waters were lower than the young water fraction (37 %) in branch xylem waters. The new water fraction (an indicator of water ≤ 2 weeks old in this study) was estimated to be 12 % for branch xylem waters, while there was no significant evidence for new water in stream or lysimeter waters from 1 m depth. Our results indicate that the source of water for trees in this system varied seasonally, such that recent precipitation may be more immediately taken up by shallow tree roots. In comparison, the source of water for soils and streams did not vary seasonally, such that precipitation may mix and reside in soils and take longer to transit into the stream. Our insights into the seasonal origins and ages of water in soils, streams, and vegetation in this humid tropical montane cloud forest add to understanding of the mechanisms that govern the partitioning of water moving through different ecosystems.

The ability to maintain functional hepatocytes has important implications for bioartificial liver development, cell-based therapies, drug screening, and tissue engineering. Several approaches can be used to restore hepatocyte function in vitro, including coating a culture substrate with extracellular matrix (ECM), encapsulating cells within biomimetic gels (Collagen- or Matrigel-based), or co-cultivation with other cells. This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids. These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors. We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes. We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor (HGF) into microcapsules and inhibiting transforming growth factor (TGF)-β1 signaling. Overall, bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering, regenerative medicine, and drug testing applications.

Abstract Schizophrenia is a debilitating psychiatric disorder associated with a reduced fertility and decreased life expectancy, yet common predisposing variation substantially contributes to the onset of the disorder, which poses an evolutionary paradox. Previous research has suggested balanced selection, a mechanism by which schizophrenia risk alleles could also provide advantages under certain environments, as a reliable explanation. However, recent studies have shown strong evidence against a positive selection of predisposing loci. Furthermore, evolutionary pressures on schizophrenia risk alleles could have changed throughout human history as new environments emerged. Here in this study, we used 1000 Genomes Project data to explore the relationship between schizophrenia predisposing loci and recent natural selection (RNS) signatures after the human diaspora out of Africa around 100,000 years ago on a genome-wide scale. We found evidence for significant enrichment of RNS markers in derived alleles arisen during human evolution conferring protection to schizophrenia. Moreover, both partitioned heritability and gene set enrichment analyses of mapped genes from schizophrenia predisposing loci subject to RNS revealed a lower involvement in brain and neuronal related functions compared to those not subject to RNS. Taken together, our results suggest non-antagonistic pleiotropy as a likely mechanism behind RNS that could explain the persistence of schizophrenia common predisposing variation in human populations due to its association to other non-psychiatric phenotypes.

En este trabajo pretendemos mostrar que la influyente tesis historiográfica de la “filosofía como forma de vida” de Pierre Hadot, según la cual el sello distintivo de la filosofía antigua fue la consistencia entre vida y doctrina, no es una tesis empírica rastreable históricamente, sino un ejemplar más de la denominada “falacia normativista” a través de la cual Hadot proyectó su concepción de la filosofía proveniente del monacato católico y del existencialismo. Consideramos que sin este importante apoyo el ideal mismo de consistencia entre vida y doctrina pierde una de sus principales bazas. Finalmente, y apelando a evidencia empírica reciente, mostramos que dicho ideal tampoco concreta en nuestros días.

La neoplasia ginecológica más frecuente son los leiomiomas uterinos, tumores benignos hormonodependientes que se generan del músculo liso del miometrio. Presentan una alta incidencia en mujeres en edad reproductiva entre la cuarta y quinta década de la vida y suelen disminuir con la menopausia. Generalmente son asintomáticos, pero a menudo se pueden acompañar de dismenorrea, metrorragia o infertilidad. El estudio inicial para su caracterización es la ecografía transvaginal; sin embargo, la resonancia magnética tiene un alto valor diagnóstico, ya que permite una evaluación más específica sobre el tipo, ubicación y número de leiomiomas, así como también permite identificar el tipo de degeneración y diferenciar entre leiomiomas y sus lesiones imitadoras. El objetivo principal de este manuscrito es abordar las principales características en resonancia magnética entre los distintos tipos de degeneración leiomiomatosa, siendo esta una causa de posible dolor abdominal y pélvico agudo.

Fluorescence lifetime imaging of the co-enzyme reduced nicotinamide adenine dinucleotide (NADH) offers a label-free approach for detecting cellular metabolic perturbations. However, the relationships between variations in NADH lifetime and metabolic pathway changes are complex, preventing robust interpretation of NADH lifetime data relative to metabolic phenotypes. Here, a three-dimensional convolutional neural network (3D CNN) trained at the cell level with 3D NAD(P)H lifetime decay images (two spatial dimensions and one time dimension) was developed to identify metabolic pathway usage by cancer cells. NADH fluorescence lifetime images of MCF7 breast cancer cells with three isolated metabolic pathways, glycolysis, oxidative phosphorylation, and glutaminolysis were obtained by a multiphoton fluorescence lifetime microscope and then segmented into individual cells as the input data for the classification models. The 3D CNN models achieved over 90% accuracy in identifying cancer cells reliant on glycolysis, oxidative phosphorylation, or glutaminolysis. Furthermore, the model trained with human breast cancer cell data successfully predicted the differences in metabolic phenotypes of macrophages from control and POLG-mutated mice. These results suggest that the integration of autofluorescence lifetime imaging with 3D CNNs enables intracellular spatial patterns of NADH intensity and temporal dynamics of the lifetime decay to discriminate multiple metabolic phenotypes. Furthermore, the use of 3D CNNs to identify metabolic phenotypes from NADH fluorescence lifetime decay images eliminates the need for time- and expertise-demanding exponential decay fitting procedures. In summary, metabolic-prediction CNNs will enable live-cell and in vivo metabolic measurements with single-cell resolution, filling a current gap in metabolic measurement technologies.

Currently, the composite industry is focusing on more environmentally friendly resources in order to generate a new range of biobased materials. In this manuscript, we present a new work using lignocellulosic wastes from the paper industry to incorporate into biobased epoxy systems. The manufactured materials were composed of kraft lignin, glass fiber, and a sustainable epoxy system, obtaining a 40% biobased content. Using a vacuum infusion process, we fabricated the composites and analyzed their mechanical and UV resistance properties. The findings reveal a significant correlation between the lignin content and flexural modulus and strength, showing an increase of 69% in the flexural modulus and 134% in the flexural strength with the presence of 5% of lignin content. Moreover, it is necessary to highlight that the presence of synthesized lignin inhibits the UV degradation of the biobased epoxy coating. We propose that the use of lignocellulosic-based wastes could improve the mechanical properties and generate UV resistance in the composite materials.

El tamizaje de cardiopatía congénita neonatal por oximetría de pulso es una práctica preventiva utilizada en todo el mundo y reconocida como un logro de la salud pública, que ha demostrado ser un método eficaz, no invasivo y de bajo costo, que, además, es bien tolerado por los recién nacidos para detectar cardiopatías congénitas en las primeras horas del nacimiento Por lo anterior, el objetivo de este trabajo fue identificar la efectividad de la oximetría de pulso como tamizaje de cardiopatías congénitas en recién nacidos. Por ello, se realizó una búsqueda sistemática de estudios clínicos controlados y estudios observacionales sobre cardiopatías congénitas en MEDLINE vía PubMed, EMBASE vía Ovid, LILACS y CENTRAL. La valoración de riesgo de sesgo se realizó con QUADAS-2. Se hizo síntesis narrativa de los hallazgos. La búsqueda arrojó 18 345 títulos; en total quince estudios cumplieron con los criterios de inclusión. Los datos se analizaron en una muestra de 286 731 recién nacidos en todos los estudios incluidos. Los resultados de los estudios fueron publicados entre 2015 y 2021, abarcando países europeos, Medio Oriente y Estados Unidos. Los análisis de precisión diagnóstica reportados, indican una especificidad superior al 95%. La sensibilidad tuvo una mayor variabilidad. Como conclusión, se tiene que la oximetría de pulso es una herramienta no invasiva, económica y útil que coadyuva en la detección precoz de cardiopatías congénitas en recién nacidos, la cual es altamente específica, y tiene una sensibilidad moderada y una tasa general baja de falsos positivos.

Objective To determine the association between the ABO blood group and preeclampsia. Methods This is a case-control study that included patients with (n = 253) and without (n = 457) preeclampsia/eclampsia in Northeastern Mexico. Data were obtained from electronic medical records. Binary multiple logistic regression analysis was used for analyzing the association between the ABO blood group and preeclampsia according to parity status while adjusting for potential confounders. Results Blood groups A, B, and AB showed adjusted odds ratios of 0.6 (95%CI 0.3-1.0), 1.1 (95%CI 0.6-2.2), and 0.3 (95%CI 0.1-1.1) in multiparous women, respectively. No association was found in nulliparous women either. Conclusions ABO blood groups were not associated with preeclampsia in Mexican women.

Los proyectos agroindustriales están destacándose frente a otros sectores debido al componente de desarrollo social y económico que tienen con poblaciones vulnerables a nivel rural. Entre estos proyectos, las organizaciones piscícolas recurren cada vez más a entornos académicos, con el objetivo de aumentar el desempeño organizacional debido a la complejidad de los mercados. En este sentido, se requiere analizar el papel de variables como la asociatividad y su relación con el desempeño y para estos fines se emplea el análisis factorial confirmatorio y un estudio correlacional, que permitan observar cómo la asociatividad puede ser un elemento que potencie los resultados de estas organizaciones. Así, los resultados han demostrado que los ítems utilizados explican en un 62,24 % el constructo de la asociatividad (KMO = 0,789) y el desempeño organización (KMO = 0,848). El índice de correlación de Pearson entre la asociatividad y el desempeño fue de 72,4 % y de p-valor < 0,005, lo que indica una relación moderada entre los constructos. Los hallazgos principales destacan que acceder a ventajas de asociatividad, capacitaciones conjuntas y recibir instrucciones vinculadas para mejorar los procesos son componentes clave de la asociatividad que propician el desempeño en las organizaciones analizadas.