bluuebunny/crossref_metadata_2025 huggingface dataset:
Ruta integradora para la gestión de la evaluación - RIGE
Authors: Orjuela Roa Cristian Harrison , Lesmes Martínez Óscar Mauricio , Castañeda Polando Juan  Gabriel
Published: December 2023

Colombia cuenta con un sistema de evaluación formalmente establecido, objetivo y basado en criterios estandarizados. Sin embargo, en términos de evaluación educativa existen grandes desafíos y retos para este sistema, principalmente por la coherencia entre lo teórico y lo práctico, los cuestionamientos sobre cómo evaluar y los enfoques tradicionales. Esta investigación de carácter descriptivo procedimental presenta una Ruta Integradora para la Gestión de la Evaluación (RIGE), construida a partir de una revisión documental, en procura de un referente teórico-práctico para que las instituciones educativas reflexionen sobre la pertinencia de las acciones evaluativas, mejoren su gestión, los procesos de regulación continua y tomen decisiones con un mayor grado de información en procura de procesos de mejoramiento más estructurados.
Generación del conocimiento sobre la enseñanza-aprendizaje virtual en educación superior: aspectos emergentes
Authors: Nuñez Manzueta Ana María , Canelón Pérez Jesús Eduardo
Published: December 2023

El avance de las Tecnologías de la Información y la Comunicación (TIC) han transformado la educación superior, especialmente en el ámbito de la enseñanza-aprendizaje virtual. En este contexto de constante evolución, es importante explorar los aspectos emergentes en la generación de conocimiento sobre la educación virtual en la educación superior. Se utilizó el método de análisis documental, recopilando información de los últimos cinco años. Los resultados demostraron que la generación de conocimiento, en estudios doctorales, es fundamental para la educación. Se emplearon diversos enfoques metodológicos y técnicas de recolección de datos para abordar temas relacionados con la educación superior y las TIC. Las conclusiones resaltan la importancia de la investigación en el ámbito educativo y sus implicaciones prácticas, reflejando los desafíos y oportunidades de la educación en la era digital. La generación de conocimiento es esencial para mejorar la práctica educativa y orientar las políticas y prácticas en este campo. Se observa una falta de consideración del construccionismo social como perspectiva teórica, esto limita la comprensión de fenómenos sociales y la interpretación de la realidad. Esta perspectiva puede enriquecer la investigación al reconocer la importancia de la participación, la interacción y la reflexión crítica en el proceso de investigación educativa.
Envejecimiento y lenguaje: cambios morfológicos y estrategias para la intervención.
Authors: Sosa Alejandra Edith
Published: December 2023

En los últimos años, ha existido un interés creciente por entender la naturaleza del lenguaje en el envejecimiento normal. Existen diversas investigaciones y teorías que exponen los cambios que se producen en los diferentes niveles del lenguaje, a saber, nivel morfosintáctico, fonológico, léxico, discursivo. Estos cambios estarían relacionados con el declive de la memoria operativa y la velocidad de procesamiento. La necesidad de realizar una revisión bibliográfica teórica sobre esta temática se sustenta en dos razones esenciales, la primera es la trascendencia de la comunicación y del lenguaje para el individuo; la segunda se centra en cambiar la mirada de la perdida de la capacidad comunicativa a buscar las posibilidades y alternativas para conservarla. El objetivo de este trabajo fue describir los cambios asociados con la edad en el lenguaje y buscar estrategias  para preservar el mismo. Se proponen diversas actividades que estimulen la neuroplasticidad neuronal y aumenten la reserva cognitiva en los adultos mayores. Las mismas tienen como objetivo trabajar sobre los déficits descriptos anteriormente y que han sido propuestos como responsables del declive de los distintos niveles del lenguaje.
Formación bilingüe en niños y niñas sordas a través de la literatura infantil
Authors: Uran Loaiza Ana Jasmin , Ramírez Gómez Karen Eliana , Rincón Bustos Martha Lucia
Published: December 2023

El presente artículo investigativo evidencia los resultados parciales de la etapa de pilotaje de la propuesta de investigación observación acción en el abordaje fonoaudiológico y pedagógico, en niñas y niños sordos inmersos en un contexto bilingüe, por medio del uso de la literatura infantil acompañada de estrategias/recursos lingüísticos y cognitivos. A fin de evidenciar el impacto que tiene el trabajo con la literatura infantil en el aprendizaje del español escrito como segunda lengua. Se conto con la participación de diez niños y niñas sordos que cursaban los niveles de prescolar y ciclo uno en una serie de talleres durante quince semanas que involucraban actividades relacionadas con la literatura infantil y los momentos de antes, durante y después de la lectura. Entre los resultados se evidencia fortalecimiento en la adquisición y consolidación de conceptos, pertinencia del uso de clave de color en el procesamiento gramatical, uso de herramientas metacognitivas en los procesos de comprensión lectora. Tras los resultados obtenidos se puede concluir que esta iniciativa permitió la interiorización de manera efectiva la macro estructura de la historia, asociado a la capacidad de evocarla y descrniños el uso de la tabla cognitiva como estrategia relevante para la representación escrita con su correspondiente en LSC,  progreso evidente en la precisión en el rastreo en la tabla cognitiva, y una disminución de la latencia de la respuesta tras los tiempos de implementación de las sesiones. Finalmente se destaca como la mediación de la literatura infantil , como eje transversal que favorece desde todas sus dimensiones,la formación del sujeto Sordo bilingüe.
Atención del Trastorno del espectro autista y epilepsia a través de Sistemas Aumentativos/Alternativos de Comunicación
Authors: Cano-Villagrasa Alejandro , Moya-Faz Francisco José , Porcar-Gozalbo Nadia , López-Zamora Miguel
Published: December 2023

El incremento de la prevalencia de los perfiles clínicos de personas con TEA y epilepsia en la etapa infantil ha aumentado en los últimos años, describiendo una problemática en su evaluación e intervención en las competencias lingüísticas. Esta población muestra graves alteraciones en el lenguaje expresivo que abarcan diferentes dimensiones de este como la fonología, la semántica, la morfosintaxis, la pragmática y la comprensión auditiva. Todo ello hace que estos usuarios muestren alteraciones significativas en su comunicación y expresión del lenguaje, lo que dificulta significativamente su autonomía y calidad de vida. Por ello, según la literatura científica, uno de los planes de intervención más efectivo que disponemos en la actualidad es el uso de los Sistemas Aumentativos y/o Alternativos de Comunicación (SAAC), los cuales han demostrado en esta población que permiten aumentar su capacidad comunicativa y resolver situaciones lingüísticas con éxito. Es por lo que los profesionales de la salud deben tener un plan de evaluación e intervención adecuado que permita solventar las necesidades comunicativas de las personas con TEA y epilepsia en la etapa infantil. Por ende, este trabajo tuvo el objetivo de reflexionar y proporcionar una revisión de la atención de la población infantil con TEA y epilepsia a través del uso de los SAACs. Para ello, se llevó a cabo una revisión narrativa de la literatura científica publicada hasta el momento, con la lectura de 51 artículos de investigación sobre la atención de la población infantil con TEA y epilepsia. Los resultados indicaron que el protocolo de evaluación para su implementación debe seguir una serie de pasos como son: Recogida de información, Valoración de la persona, Valoración del entorno cercano, Selección del vocabulario, Selección de los reforzadores, Análisis de los sistemas de comunicación, Toma de decisiones y Evaluación de la efectividad del sistema de comunicación. Asimismo, el uso de SAACs en este colectivo mejora de forma significativa la comunicación funcional en diferentes contextos y entornos. En conclusión, se debe llevar a cabo una atención multidisciplinar para mejorar las competencias lingüísticas de las personas con TEA y epilepsia.
Electroestimulación del nervio vago. Importantes aplicaciones en fisioterapia
Authors: Rincón Castillo Emerson Julian
Published: December 2023

Introducción: La Electroestimulación del Nervio Vago (ENV), durante los últimos años ha demostrado resultados positivos en la atención de pacientes con depresión, epilepsia y migraña. Actualmente los efectos de la ENV están siendo investigados en otras patologías como en el accidente cerebrovascular, el síndrome de fibromialgia y para el tratamiento de dolor crónico. Objetivo: El propósito de esta revisión descriptiva es proporcionar al fisioterapeuta una actualización sobre conceptos necesarios y en evolución sobre la electroestimulación del nervio vago, dando a conocer las potenciales aplicaciones para la profesión de fisioterapia. Metodología: Este artículo de revisión descriptiva se realizó a través de una búsqueda de la literatura científica disponible en las bases de datos como Google Académico, Scielo, Dialnet Plus, ScienceDiret, y PubMed, de los cuales se seleccionaron para accidente cerebrovascular un total de 8 artículos, 2 artículos para fibromialgia y 2 artículos para dolor crónico.    Discusión: El presente artículo describe las potencialidades que tiene para el fisioterapeuta el uso de la ENV para el tratamiento del síndrome de fibromialgia y el dolor crónico, además, de la rehabilitación de las secuelas funcionales del paciente post ACV. Conclusiones: La ENV se encauza a hacer una opción terapéutica válida y segura para el tratamiento y rehabilitación de diferentes patologías que en general afectan al sistema nervioso, patologías que tienen gran impacto en la calidad de vida de los pacientes, convirtiéndose la ENV en una de las potenciales alternativas terapéuticas para estos pacientes.
Percepción de salud, bienestar, conciencia corporal y nivel de actividad física en pacientes oncológicos infantiles
Authors: Escobar Insuasti Mayra Valeria , Grijalba Vallejo Karen Elena , Davila Morales Leidy Estefania , Maca Chamorro Fredy Andres , Álvarez María del Rosario
Published: December 2023

Introducción: El cáncer es un término que designa un amplio grupo de enfermedades las cuales afectan a cualquier parte del organismo. En el departamento de Nariño el cáncer infantil presenta alta incidencia, específicamente para diagnósticos de Leucemia Linfoblástica Aguda (LLA) y Linfomas. En los niños, este diagnóstico ejerce una tensión física y emocional que puede llegar a provocar alteraciones en su bienestar, conciencia corporal y niveles de actividad física, siendo estos aspectos fundamentales del movimiento corporal humano. Objetivo: Determinar la percepción de salud, bienestar, conciencia corporal y nivel de actividad física en pacientes oncológicos infantiles del Hospital Infantil Los Ángeles. Método: Estudio descriptivo transversal con enfoque cuantitativo, con una muestra de 30 usuarios infantiles con diagnósticos de LLA y Linfomas atendidos en Hospital Infantil Los Ángeles Resultados: El género masculino prevalece, así como el estrato socioeconómico bajo – bajo. En las características clínicas, los medicamentos de mayor uso son los citotóxicos y los síntomas prevalentes son dolor de cabeza y náuseas. Para la percepción de salud y bienestar el 13% de la población presenta una percepción regular, al igual que la conciencia corporal interoceptiva donde el 80% presenta un nivel de conciencia corporal regular. Se evidencian niveles bajos y moderados de actividad física. Conclusiones: Los niños presentan en menor proporción inadecuada percepción de salud relacionada con su calidad de vida. La conciencia corporal interoceptiva se ve alterada en componentes de: conciencia emocional, regulación de la atención y escuchar al cuerpo. La población oncológica infantil presenta niveles de actividad física baja.
dermatoglifia dactilar herramienta de reconocimiento de la hipertensión arterial
Authors: Castro Laura Elizabeth , Sarmiento Soler Iván David
Published: December 2023

Introducción. La hipertensión arterial es una patología crónica que genera complicaciones de salud, deteriora la calidad de vida y tiene altos costos en el sistema sanitario; su detección suele ser tardía por presentar síntomas silenciosos. La dermatoglifia es una herramienta de detección temprana que puede responder a la necesidad de identificar predisposición genética a la enfermedad y de esta manera realizar acciones de prevención. Objetivo. Identificar la evidencia científica en dermatoglifia dactilar como herramienta de reconocimiento de riesgo de hipertensión arterial.  Métodos. Se realizó una revisión sistemática, adoptando la metodología prisma en cuatro bases de datos (Pubmed, Sciencedirect, BVS y Scopus). Los artículos que fueron incluidos se les hizo evaluación de sesgo de Cochrane y se evaluó bajo Scottish Intercollegiate Guidelines Network, con nivel de evidencia y recomendación. Resultados. Se encontraron finalmente 19 artículos correspondientes a la hipertensión arterial. Mostrando una clasificación de cuatro artículos en una categoría 2++, cinco de ellos fueron 2+ y 11 artículos en 2- para hipertensión arterial, con un nivel de recomendación C y D. La evidencia demuestra la relación entre los dermatoglifos y la presencia de la hipertensión arterial, presentando mayor número de crestas en las huellas digitales y verticilos. Conclusión. La dermatoglifia es una herramienta de reconocimiento a la hipertensión arterial, estableciendo un instrumento de bajo costo, confiable y no invasiva, facilitando la detección temprana de la enfermedad y prevenir complicaciones asociadas.
Efecto de un Programa de Rehabilitación Neuropsicológica del Funcionamiento Ejecutivo en Un Caso con Trastorno Neurocognitivo Leve debido a SAHOS
Authors: Quintero Giraldo Irma Vanessa , Uribe Lopera Adrián Felipe , Carvajal Castrillón Julián Santiago , Franco García Sergio
Published: December 2023

La rehabilitación neuropsicológica de los pacientes con apnea e hipoapnea obstructiva del sueño (SAHOS) está poco documentada, sin embargo, las secuelas de esta enfermedad son ampliamente conocidas, pues afecta diferentes esferas de quien la padece, incluyendo funciones cognitivas como atención, memoria, lenguaje y funciones ejecutivas, de ahí la importancia de la intervención neuropsicológica. El objetivo de esta investigación era establecer el efecto de un programa de rehabilitación neuropsicológica de las funciones ejecutivas para mejorar la funcionalidad en un caso único de trastorno neurocognitivo menor debido a SAHOS. Es un paciente masculino de 51 años de edad, bachiller, con diagnóstico de Trastorno neurocognitivo leve debido a SAHOS: Disfunción ejecutiva severa y trastorno de ansiedad no especificado. Es un estudio cuasiexperimental de caso único con diseño A-B no reversión, las mediciones repetidas se realizaron con los instrumentos: BRIEF A y escala de ansiedad de Hamilton. La intervención neuropsicológica se realizó bajo el modelo de Sholberg y Mateer utilizando actividades de la plataforma Cognifit (40 sesiones), tareas de lápiz y papel (6 sesiones) e implementación de la guía terapéutica en casa. Para el análisis de los resultados se utilizaron el análisis visual y métodos estadísticos como: El porcentaje de datos no solapados, el porcentaje de datos que exceden la mediana y el no solapamiento de todos los pares, que arrojaron datos efectividad del tratamiento tanto para el paciente como para el familiar. En la escala de Hamilton no se evidenciaron cambios.
Lucerne meal in the diet of indigenous chickens: a review
Authors: Ginindza Muzi M.
Published: December 2023

Indigenous chicken production consists of an array of activities important to smallholder poultry farmers in Africa. One of the many factors influencing their production and threating the local food security is in the area of nutrition, particularly, that related to protein supplementation. The available feed resources to farmers are not enough to sustain the productivity of the chickens. Hence, the chickens’ diets often require nutritional supplementation. There is therefore an urgent need for the validation of locally grown feed ingredients to improve the sustainability of poultry production in sub-Saharan Africa. A dietary ingredient that may be used in the diets of chickens is lucerne (Medicago sativa), which is also known as alfalfa. In South Africa, lucerne is the most cultivated forage legume and approximately 1.3 million metric tonnes of lucerne are produced per year. Lucerne has high nutritional value, as it is a source of protein, amino acids, vitamins, and fatty acids. The potential of lucerne as a feed resource for indigenous chickens should, therefore, be investigated so that strategies to improve the nutrition of such chickens can be developed. The purpose of this review was to highlight lucerne as a potential dietary ingredient for indigenous chickens and discuss its effects on the productivity of broilers, egg-layers, and dual-purpose chickens.
Ultrasensitive biosensing platform for Mycobacterium tuberculosis detection based on functionalized graphene devices
Authors: Seo Giwan , Lee Geonhee , Kim Wooyoung , An Inyoung , Choi Myungwoo , Jang Sojeong , Park Yeon-Joon , Lee Jeong-O. , Cho Donghwi , Park Edmond Changkyun
Published: December 2023

Tuberculosis (TB) has high morbidity as a chronic infectious disease transmitted mainly through the respiratory tract. However, the conventional diagnosis methods for TB are time-consuming and require specialists, making the diagnosis of TB with point-of-care (POC) detection difficult. Here, we developed a graphene-based field-effect transistor (GFET) biosensor for detecting the MPT64 protein of Mycobacterium tuberculosis with high sensitivity as a POC detection platform for TB. For effective conjugation of antibodies, the graphene channels of the GFET were functionalized by immobilizing 1,5-diaminonaphthalene (1,5-DAN) and glutaraldehyde linker molecules onto the graphene surface. The successful immobilization of linker molecules with spatial uniformity on the graphene surface and subsequent antibody conjugation were confirmed by Raman spectroscopy and X-ray photoelectron spectroscopy. The GFET functionalized with MPT64 antibodies showed MPT64 detection with a detection limit of 1 fg/mL in real-time, indicating that the GFET biosensor is highly sensitive. Compared to rapid detection tests (RDT) and enzyme-linked immunosorbent assays, the GFET biosensor platform developed in this study showed much higher sensitivity but much smaller dynamic range. Due to its high sensitivity, the GFET biosensor platform can bridge the gap between time-consuming molecular diagnostics and low-sensitivity RDT, potentially aiding in early detection or management of relapses in infectious diseases.
Exploring undergraduates’ perceptions of and engagement in an AI-enhanced online course
Authors: Sadegh-Zadeh Seyed-Ali , Movahhedi Tahereh , Hajiyavand Amir M. , Dearn Karl D.
Published: December 2023

In the age of globalization, an internet connection has become essential for enhancing various human activities across the economic, cultural, and defense sectors, among others. This is particularly true for online classrooms. Microsoft Teams, a widely used digital education platform, provides capabilities that allow online teachers to facilitate better interactions and create more effective learning environments in online settings. This study aimed to explore students’ perceptions of synchronous online learning that occurred in an AI-enhanced online course, delivered using MS Teams. As an explorative study that examines the educational intersection of engineering and artificial intelligence, it represents the convergence of these two branches of learning and thus enriches both fields. The research involved 35 online students at the Staffordshire University, with data collected via online questionnaires to gather information about students’ perceptions of online learning through Microsoft Teams. After completing the online course materials, the questionnaires were distributed to students via Google Forms. The data were then descriptively analyzed. The study’s findings revealed that although online learning through Microsoft Teams was a novel experience for the students, the platform’s interactive and engaging learning environment motivated them to participate more actively, ultimately leading to a better comprehension of the course materials. Incorporating AI-enhanced features within the Microsoft Teams platform further augmented the online learning experience, as students appreciated the personalized learning recommendations and real-time feedback, which showcases the synergistic potential of AI and education in the digital age.
The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer
Authors: Li Changlin , Zhang Jiao , Dionigi Gianlorenzo , Sun Hui
Published: December 2023

Background

Subclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC).

Materials and methods

A retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways.

Results

In total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028–1.327]; P=0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089–1.520]; P=0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032–1.852], P=0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells.

Conclusion

Subclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism.
Study on the evolution law and stage response relationship between meteorological elements and hydrological drought in Xiangtan area
Authors: Wan Fang , Han Wenhao , Long Qiubo , Wang Weijun , Wang Guoqing , Zhang Fei
Published: December 2023

Studying the propagation law and response relationship between meteorological elements and hydrological drought is conducive to exploring the propagation mechanism and transmission time of drought, and providing a basis for reasonable and efficient drought relief work. In this paper, the area above Xiangtan station is taken as the research area, and the temperature and precipitation are selected as the meteorological elements. The standardized flow index (SDI) is used to characterize the hydrological drought. The linear regression method and Mann-Kendall trend test are used to analyze the evolution sequence of meteorological elements and hydrological drought at different scales. The characteristics and laws of drought propagation are revealed, and the hydrological drought is divided into stages by combining the ordered cluster analysis method and the sliding t-test method. The Pearson correlation analysis method is used to analyze the stage correlation degree between meteorological elements and hydrological drought, reflecting the response relationship between meteorological elements and hydrological drought under different types and different scales, and the response period of hydrological drought to meteorological elements at different time scales is obtained. Studying the development trend and evolution law of meteorological elements and hydrological drought, and deeply exploring the phased response relationship are conducive to improving the drought resistance ability and drought disaster reduction management ability of Xiangtan area.
Spatial modelling of the tumor microenvironment from multiplex immunofluorescence images: methods and applications
Authors: Kumar Gayatri , Pandurengan Renganayaki Krishna , Parra Edwin Roger , Kannan Kasthuri , Haymaker Cara
Published: December 2023

Spatial modelling methods have gained prominence with developments in high throughput imaging platforms. Multiplex immunofluorescence (mIF) provides the scope to examine interactions between tumor and immune compartment at single cell resolution using a panel of antibodies that can be chosen based on the cancer type or the clinical interest of the study. The markers can be used to identify the phenotypes and to examine cellular interactions at global and local scales. Several translational studies rely on key understanding of the tumor microenvironment (TME) to identify drivers of immune response in immunotherapy based clinical trials. To improve the success of ongoing trials, a number of retrospective approaches can be adopted to understand differences in response, recurrence and progression by examining the patient’s TME from tissue samples obtained at baseline and at various time points along the treatment. The multiplex immunofluorescence (mIF) technique provides insight on patient specific cell populations and their relative spatial distribution as qualitative measures of a favorable treatment outcome. Spatial analysis of these images provides an understanding of the intratumoral heterogeneity and clustering among cell populations in the TME. A number of mathematical models, which establish clustering as a measure of deviation from complete spatial randomness, can be applied to the mIF images represented as spatial point patterns. These mathematical models, developed for landscape ecology and geographic information studies, can be applied to the TME after careful consideration of the tumor type (cold vs. hot) and the tumor immune landscape. The spatial modelling of mIF images can show observable engagement of T cells expressing immune checkpoint molecules and this can then be correlated with single-cell RNA sequencing data.
Blocking P2Y2 purinergic receptor prevents the development of lipopolysaccharide-induced acute respiratory distress syndrome
Authors: Kargarpour Zahra , Cicko Sanja , Köhler Thomas C. , Zech Andreas , Stoshikj Slagjana , Bal Christina , Renner Andreas , Idzko Marco , El-Gazzar Ahmed
Published: December 2023

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality resulting from a direct or indirect injury of the lung. It is characterized by a rapid alveolar injury, lung inflammation with neutrophil accumulation, elevated permeability of the microvascular-barrier leading to an aggregation of protein-rich fluid in the lungs, followed by impaired oxygenation in the arteries and eventual respiratory failure. Very recently, we have shown an involvement of the Gq-coupled P2Y2 purinergic receptor (P2RY2) in allergic airway inflammation (AAI). In the current study, we aimed to elucidate the contribution of the P2RY2 in lipopolysaccharide (LPS)-induced ARDS mouse model. We found that the expression of P2ry2 in neutrophils, macrophages and lung tissue from animals with LPS-induced ARDS was strongly upregulated at mRNA level. In addition, ATP-neutralization by apyrase in vivo markedly attenuated inflammation and blocking of P2RY2 by non-selective antagonist suramin partially decreased inflammation. This was indicated by a reduction in the number of neutrophils, concentration of proinflammatory cytokines in the BALF, microvascular plasma leakage and reduced features of inflammation in histological analysis of the lung. P2RY2 blocking has also attenuated polymorphonuclear neutrophil (PMN) migration into the interstitium of the lungs in ARDS mouse model. Consistently, treatment of P2ry2 deficient mice with LPS lead to an amelioration of the inflammatory response showed by reduced number of neutrophils and concentrations of proinflammatory cytokines. In attempts to identify the cell type specific role of P2RY2, a series of experiments with conditional P2ry2 knockout animals were performed. We observed that P2ry2 expression in neutrophils, but not in the airway epithelial cells or CD4+ cells, was associated with the inflammatory features caused by ARDS. Altogether, our findings imply for the first time that increased endogenous ATP concentration via activation of P2RY2 is related to the pathogenesis of LPS-induced lung inflammation and may represent a potential therapeutic target for the treatment of ARDS and predictably assess new treatments in ARDS.
Oncogenes and cancer associated thrombosis: what can we learn from single cell genomics about risks and mechanisms?
Authors: Tawil Nadim , Mohammadnia Abdulshakour , Rak Janusz
Published: December 2023

Single cell analysis of cancer cell transcriptome may shed a completely new light on cancer-associated thrombosis (CAT). CAT causes morbid, and sometimes lethal complications in certain human cancers known to be associated with high risk of venous thromboembolism (VTE), pulmonary embolism (PE) or arterial thromboembolism (ATE), all of which worsen patients’ prognosis. How active cancers drive these processes has long evaded scrutiny. While “unspecific” microenvironmental effects and consequences of patient care (e.g., chemotherapy) have been implicated in pathogenesis of CAT, it has also been suggested that oncogenic pathways driven by either genetic (mutations), or epigenetic (methylation) events may influence the coagulant phenotype of cancer cells and stroma, and thereby modulate the VTE/PE risk. Consequently, the spectrum of driver events and their downstream effector mechanisms may, to some extent, explain the heterogeneity of CAT manifestations between cancer types, molecular subtypes, and individual cases, with thrombosis-promoting, or -protective mutations. Understanding this molecular causation is important if rationally designed countermeasures were to be deployed to mitigate the clinical impact of CAT in individual cancer patients. In this regard, multi-omic analysis of human cancers, especially at a single cell level, has brought a new meaning to concepts of cellular heterogeneity, plasticity, and multicellular complexity of the tumour microenvironment, with profound and still relatively unexplored implications for the pathogenesis of CAT. Indeed, cancers may contain molecularly distinct cellular subpopulations, or dynamic epigenetic states associated with different profiles of coagulant activity. In this article we discuss some of the relevant lessons from the single cell “omics” and how they could unlock new potential mechanisms through which cancer driving oncogenic lesions may modulate CAT, with possible consequences for patient stratification, care, and outcomes.
Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit
Authors: Chiscano-Camón Luis , Ruiz-Rodriguez Juan Carlos , Plata-Menchaca Erika P. , Martin Laura , Bajaña Ivan , Martin-Rodríguez Cristina , Palmada Clara , Ferrer-Costa Roser , Camos Silvia , Villena-Ortiz Yolanda , Ribas Vicent , Ruiz-Sanmartin Adolf , Pérez-Carrasco Marcos , Ferrer Ricard
Published: December 2023

Objectives

To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency.

Design

Prospective, observational, single-center study.

Setting

Intensive Care Unit (ICU), Vall d’Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021.

Patients

Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included.

Interventions

Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients.

Measurement

Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2–5 mg/L; (normal plasma concentration: > 5 mg/L).

Main results

Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1–4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10–22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients.

Conclusion

This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.
Ubiquitin signaling in pancreatic ductal adenocarcinoma
Authors: Lv Shengnan , Zhang Jian , Peng Xinyu , Liu Huan , Liu Yan , Wei Feng
Published: December 2023

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.
Genetic landscape of Parkinson’s disease and related diseases in Luxembourg
Authors: Landoulsi Zied , Pachchek Sinthuja , Bobbili Dheeraj Reddy , Pavelka Lukas , May Patrick , Krüger Rejko ,   the NCER-PD Consortium
Published: December 2023

Objectives

To explore the genetic architecture of PD in the Luxembourg Parkinson’s Study including cohorts of healthy people and patients with Parkinson’s disease (PD) and atypical parkinsonism (AP).

Methods

809 healthy controls, 680 PD and 103 AP were genotyped using the Neurochip array. We screened and validated rare single nucleotide variants (SNVs) and copy number variants (CNVs) within seven PD-causing genes (LRRK2, SNCA, VPS35, PRKN, PARK7, PINK1 and ATP13A2). Polygenic risk scores (PRSs) were generated using the latest genome-wide association study for PD. We then estimated the role of common variants in PD risk by applying gene-set-specific PRSs.

Results

We identified 60 rare SNVs in seven PD-causing genes, nine of which were pathogenic in LRRK2, PINK1 and PRKN. Eleven rare CNVs were detected in PRKN including seven duplications and four deletions. The majority of PRKN SNVs and CNVs carriers were heterozygous and not differentially distributed between cases and controls. The PRSs were significantly associated with PD and identified specific molecular pathways related to protein metabolism and signal transduction as drivers of PD risk.

Conclusion

We performed a comprehensive genetic characterization of the deep-phenotyped individuals of the Luxembourgish Parkinson’s Study. Heterozygous SNVs and CNVs in PRKN were not associated with higher PD risk. In particular, we reported novel digenic variants in PD related genes and rare LRRK2 SNVs in AP patients. Our findings will help future studies to unravel the genetic complexity of PD.
A systematic review for the development of Alzheimer’s disease in in vitro models: a focus on different inducing agents
Authors: Prajapat Manisha , Kaur Gurjeet , Choudhary Gajendra , Pahwa Paras , Bansal Seema , Joshi Rupa , Batra Gitika , Mishra Abhishek , Singla Rubal , Kaur Harminder , Prabha Praisy K. , Patel Ajay Prakash , Medhi Bikash
Published: December 2023

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to induce in-vitro models of Alzheimer disease to investigate the efficacy of different therapeutic drugs. We screened literature from databases such as PubMed, ScienceDirect, and Google scholar, emphasizing the diverse targeting mechanisms of neuro degeneration explored in in-vitro models. The results revealed studies in which different types of chemicals and environmental agents were used for in-vitro development of Alzheimer-targeting mechanisms of neurodegeneration. Studies using chemically induced in-vitro AD models included in this systematic review will contribute to a deeper understanding of AD. However, none of these models can reproduce all the characteristics of disease progression seen in the majority of Alzheimer’s disease subtypes. Additional modifications would be required to replicate the complex conditions of human AD in an exact manner. In-vitro models of Alzheimer’s disease developed using chemicals and environmental agents are instrumental in providing insights into the disease’s pathophysiology; therefore, chemical-induced in-vitro AD models will continue to play vital role in future AD research. This systematic screening revealed the pivotal role of chemical-induced in-vitro AD models in advancing our understanding of AD pathophysiology and is therefore important to understand the potential of these chemicals in AD pathogenesis.
Neural correlate of reduced respiratory chemosensitivity during chronic epilepsy
Authors: Bhandare Amol M. , Dale Nicholas
Published: December 2023

While central autonomic, cardiac, and/or respiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP), the specific neural mechanisms that lead to SUDEP remain to be determined. In this study, we took advantage of single-cell neuronal Ca2+ imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Weeks after induction of status epilepticus (SE), when mice were experiencing recurrent spontaneous seizures (chronic epilepsy), we observed that the adaptive ventilatory responses to hypercapnia were reduced for 5 weeks after SE induction with its partial recovery at week 7. These changes were paralleled by alterations in the chemosensory responses of neurons in the retrotrapezoid nucleus (RTN). Neurons that displayed adapting responses to hypercapnia were less prevalent and exhibited smaller responses over weeks 3–5, whereas neurons that displayed graded responses to hypercapnia became more prevalent by week 7. Over the same period, chemosensory responses of the presympathetic rostral ventrolateral medullary (RVLM) neurons showed no change. Mice with chronic epilepsy showed enhanced sensitivity to seizures, which invade the RTN and possibly put the chemosensory circuits at further risk of impairment. Our findings establish a dysfunctional breathing phenotype with its RTN neuronal correlate in mice with chronic epilepsy and suggest that the assessment of respiratory chemosensitivity may have the potential for identifying people at risk of SUDEP.
Case report: Primary pleural low-grade fibromyxoid sarcoma in a 4-year-old boy with molecular confirmation
Authors: He Xiangni , Jing Wenyi , He Xin , Chen Min , Zhang Hongying
Published: December 2023

Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor, principally affecting the deep tissues of the proximal trunk and extremities in young adults. However, primary pleural LGFMS is extremely rare, and only three cases have been reported in the previous English literature without genetic confirmation. Furthermore, the historical pleural LGFMS cases were all adults, and the primary pleural LGFMS in children has never been reported to date. Here, we presented a primary pleural LGFMS in a 4-year-old boy with detailed clinical, pathological, and molecular results. Histologically, the current tumor showed typical alternating collagenous and myxoid areas, containing spindled or oval tumor cells arranged in a whorled and short fascicular pattern. In some areas, the tumor cells exhibited moderate atypia, and mitotic figures were identified but without the identification of giant collagen rosettes. Immunohistochemically, all the neoplastic cells showed strong and diffuse positivity for MUC4. Genetically, FUS gene rearrangement was revealed by fluorescence in-situ hybridization (FISH), and subsequently, next-generation sequencing (NGS) and polymerase chain reaction (PCR) further demonstrated the FUS::CREB3L2 fusion transcript. To the best of our knowledge, this is the first case of primary pleural LGFMS with the identification of FUS gene rearrangement and FUS::CREB3L2 fusion in a 4-year-old child. Our study expands the age range of pleural LGFMS and highlights the combination of morphological, immunohistochemical, and molecular analyses in such challenging cases.
Genome-wide identification of NAC transcription factors and regulation of monoterpenoid indole alkaloid biosynthesis in Catharanthus roseus
Authors: Ahmed Jawad , Sajjad Yasar , Gatasheh Mansour K. , Ibrahim Khalid Elfaki , Huzafa Muhammad , Khan Sabaz Ali , Situ Chen , Abbasi Arshad Mehmood , Hassan Amjad
Published: December 2023

NAC transcription factors (TFs) are crucial to growth and defense responses in plants. Though NACs have been characterized for their role in several plants, comprehensive information regarding their role in Catharanthus roseus, a perennial ornamental plant, is lacking. Homology modelling was employed to identify and characterize NACs in C. roseus. In-vitro propagation of C. roseus plants was carried out using cell suspension and nodal culture and were elicited with two auxin-antagonists, 5-fluoro Indole Acetic Acid (5-F-IAA) and α-(phenyl ethyl-2-oxo)-Indole-Acetic-Acid (PEO-IAA) for the enhanced production of monoterpenoid indole alkaloids (MIAs) namely catharanthine, vindoline, and vinblastine. Analyses revealed the presence of 47 putative CrNAC genes in the C. roseus genome, primarily localized in the nucleus. Phylogenetic analysis categorized these CrNACs into eight clusters, demonstrating the highest synteny with corresponding genes in Camptotheca acuminata. Additionally, at least one defense or hormone-responsive cis-acting element was identified in the promoter region of all the putative CrNACs. Of the two elicitors, 5-F-IAA was effective at 200 µM to elicit a 3.07-fold increase in catharanthine, 2.76-fold in vindoline, and 2.4-fold in vinblastine production in nodal culture. While a relatively lower increase in MIAs was recorded in suspension culture. Validation of RNA-Seq by qRT-PCR showed upregulated expression of stress-related genes (CrNAC-07 and CrNAC-24), and downregulated expression of growth-related gene (CrNAC-25) in elicited nodal culture of C. roseus. Additionally, the expression of genes involved in the biosynthesis of MIAs was significantly upregulated upon elicitation. The current study provides the first report on the role of CrNACs in regulating the biosynthesis of MIAs.
The burden of substance use and (mental) distress among asylum seekers: a cross sectional study
Authors: Solfrank Maximilian , Nikendei Christoph , Zehetmair Catharina , Friederich Hans-Christoph , Nagy Ede
Published: December 2023

Background

Asylum seekers are a particularly vulnerable population due to a wide range of external stressors. Traumatic events and difficult social/economic prospects can lead to an elevated susceptibility for substance use disorders. The aim of the present study was to determine whether asylum seekers suffering from mental or physical distress present higher levels of substance use disorder (SUD) in a state reception center in Germany and whether there are identifiable risk or protective factors.

Methods

We performed a hierarchical logistic regression on data of N = 238 people who had applied for asylum in Germany to analyze the SUD variance explanation by (1) sociodemographic, (2) flight-specific, and (3) psychometric (ERQ, SOC-9 L, SCL-K9) variables. On level (4), we included the location of data collection (walk-in clinic or accommodation,) as an indicator of individual’s need for a psychologist’s or General practitioner’s help in order to assess for the participant’s (mental) distress.

Results

Low educational level, lower sense of coherence, and mental distress (location of data collection in the psychosocial or general medical outpatient clinic) were associated with SUD. Those suffering from SUD seemed to be less aware of external stressors as SUD was also associated with low levels of reported post-migratory stress.

Discussion

The association of SUD with psychological distress and lower education reaffirms the concept that some vulnerable groups are at a higher risk for substance-related difficulties. Strengthening the sense of coherence with targeted interventions might enable at-risk groups to cope better with forthcoming burdens and help with abstaining from current or future consumption.