bluuebunny/crossref_metadata_2025 huggingface dataset:
CASA DO MIGRANTE DE FOZ DO IGUAÇU:
Authors: Amadori Rosane
Published: June 2023

O artigo aborda o tráfico de pessoas a partir dos atendimentos realizados pela Casa do Migrante de Foz do Iguaçu. O trabalho expõe o cenário do delito, no contexto das migrações e dos marcos regulatórios, com tipificação definida em âmbito internacional pelo Protocolo de Palermo, ratificado no Brasil pela Lei do Tráfico de Pessoas. O objetivo é analisar os atendimentos aos migrantes, sob o viés do enfrentamento ao tráfico de pessoas, e contribuir para a elaboração de políticas públicas para tal; este artigo traz o histórico da instituição, descreve a estrutura da Casa e relaciona os registros dos últimos cinco anos de atendimento ao fluxo fronteiriço, e sua condição de facilitador do tráfico humano, também, ao que prevê o III Plano Nacional de Enfrentamento ao Tráfico de Pessoas para as fronteiras brasileiras. Para compor o cenário de análise, o estudo utiliza informações obtidas em entrevista aberta, realizada com a coordenadora da Casa do Migrante de Foz do Iguaçu, Irmã Terezinha Mezzalira, e nos registros de atendimentos dos últimos cinco anos. Como constatação da análise, a ausência de dados e a fragilidade na tríplice fronteira, em relação ao tráfico de pessoas, um dos crimes que mais crescem em âmbito internacional.
DESCAMINHO:
Authors: Barros Junior Celso Silva , Oliveira Junior Hugo Thales de Araujo
Published: June 2023

O descaminho é problema crônico, sendo, há décadas, questão recorrente e ininterrupta na fronteira entre Brasil e Paraguai. As autoridades não parecem se preocupar em solucionar o problema do descaminho, que resulta em outros crimes, tais como corrupção, evasão de divisas e lavagem de dinheiro. Este trabalho analisa os principais aspectos do descaminho em busca de uma solução que correlacione os elementos penal, administrativo, social e econômico, através de uma abordagem contemporânea em busca da concretização do princípio da dignidade da pessoa humana, fortalecendo a economia e segurança nacionais.
Psychometric properties and measurement invariance of a European Portuguese version of the fear of COVID-19 scale
Authors: Jarego Margarida , Ferreira-Valente Alexandra , Miguel Costa Rui , Tavares Mafalda , Pais-Ribeiro José
Published: June 2023

The novelty and uncertainty of the pandemic nourished a generalized fear of the COVID-19, which seems to have exacerbated the pandemic’s negative impact. It is thus relevant to monitor fear of COVID-19 and its association with individuals’ mental health, well-being, and behaviors. Valid and reliable measures of fear of COVID-19 are necessary for that purpose. This study aimed at assessing the psychometric properties of a European Portuguese version of the Fear of COVID-19 scale (FCV-19S-P). A secondary aim was to assess FCV-19S-P’s multigroup measurement invariance (female vs. male). A sample of 572 Portuguese adults (72 % female) completed the FCV-19S-P and measures of depression, anxiety, and stress. The study results supported this version validity and reliability (Cronbach’s alpha = .84; Composite Reliability = .83), and a factorial structure similar to the original version. Fear of COVID-19 was positively associated (.23 < r < .31) with depression, anxiety, and stress. Results of the multigroup invariance analysis supported the FCV-19S-P total scalar invariance and its partial residual invariance, suggesting that this measure may be used to reach valid conclusions in respect to gender comparisons in samples of Portuguese adults in regard to group observed composite means.

El miedo generalizado de la COVID-19 parece haber exacerbado el impacto negativo de la pandemia. Por eso, es relevante monitorear el miedo de la COVID-19 y su asociación con la salud mental, el bienestar y los comportamientos de las personas, siendo necesarias medidas válidas y fiables de miedo de la COVID-19. Este estudio tuvo como objetivo evaluar las propiedades psicométricas de una versión en portugués europeo de la escala Fear of COVID-19 (FCV-19S-P). Un objetivo secundario fue evaluar la invariancia de medición transversal multigrupo de FCV-19S-P (mujeres vs. hombres). Una muestra de 572 adultos portugueses (72 % mujeres) completaron el FCV-19S-P y medidas de depresión, ansiedad y estrés. Los resultados del estudio respaldaron la validez de esta versión y fiabilidad (alfa de Cronbach = .84; confiabilidad compuesta = .83) y una estructura factorial similar a de la versión original. El miedo de la COVID-19 se asoció positivamente (.23 < r < .31) con depresión, ansiedad y estrés. Los resultados del análisis transversal de invariancia multigrupo respaldaron la invariancia escalar total de la FCV-19S-P y su invariancia residual parcial, lo que sugiere que esta medida puede usarse para llegar a conclusiones válidas con respecto a las comparaciones de género en muestras de adultos portugueses.
Evidencias de validez de la Escala de Sentimiento de Autoeficacia Docente en una muestra española
Authors: Bueno-Álvarez José-Antonio , Martín-Martín Margarita-Carmen , Navarro Asencio Enrique , Asensio-Muñoz Isabel-Inmaculada
Published: June 2023

Teachers’ sense of self-efficacy is a hard construct to measure but is important in view of to its relationship with the quality of education. This work aims to gather evidence regarding the consistency and validity of a version of the Teachers’ Sense of Efficacy Scale (TSES) for use in Spain. The data come from a Spanish group of future early-years, primary and high school teachers (N = 744), and they are analysed using a multivariate approach suitable for ordinal scales, with confirmatory factor analysis (ULSMV) and decision trees (CHAID and CART). After evaluating three measurement models, evidence for the validity of a construct structure with three factors and 17 items with acceptable fit indices is provided. In addition, the convergence and consistency of the construct are both endorsed, as is the usefulness of the items for predicting overall teacher self-efficacy in the groups of undergraduate and master’s students in the sample studied.

El sentimiento de autoeficacia docente (SAD) es un constructo de compleja medida pero relevante por su relación con la calidad de la educación. Con este trabajo se pretende acumular evidencias de consistencia y validez para su uso en España de una versión del Teachers’ Sense of Efficacy Scale (TSES). Los datos proceden de un colectivo español de futuros profesores de infantil, primaria y secundaria (N = 744) y se analizan desde un enfoque multivariado adecuado para escala ordinal, mediante análisis factorial confirmatorio (ULSMV) y árboles de decisión (CHAID y CART). Tras evaluar tres modelos de medida, se aportan evidencias de validez de una estructura del constructo en tres factores y 17 ítems, con índices de ajuste aceptables. Además, se avala tanto la convergencia y consistencia del constructo, como la utilidad de los ítems para la predicción de la autoeficacia docente global en los colectivos de estudiantes de grado y de máster que componen la muestra estudiada.
Robustness of Generalized Linear Mixed Models for Split-Plot Designs with Binary Data
Authors: Bono Roser , Alarcón Rafael , Arnau Jaume , García-Castro F. Javier , Blanca Maria J.
Published: June 2023

This paper examined the robustness of the generalized linear mixed model (GLMM). The GLMM estimates fixed and random effects, and it is especially useful when the dependent variable is binary. It is also useful when the dependent variable involves repeated measures, since it can model correlation. The present study used Monte Carlo simulation to analyze the empirical Type I error rates of GLMMs in split-plot designs. The variables manipulated were sample size, group size, number of repeated measures, and correlation between repeated measures. Extreme conditions were also considered, including small samples, unbalanced groups, and different correlation in each group (pairing between group size and correlation between repeated measures). For balanced groups, the results showed that the group effect was robust under all conditions, while for unbalanced groups the effect tended to be conservative with positive pairing and liberal with negative pairing. Regarding time and interaction effects, the results showed, for both balanced and unbalanced groups, that: (a) The test was robust with low correlation (.2), but conservative for medium values of correlation (.4 and .6), and (b) the test tended to be conservative for positive and negative pairing, especially the latter.

Este artículo examina la robustez del modelo lineal mixto generalizado (GLMM, por sus siglas en inglés). El GLMM estima efectos fijos y efectos aleatorios y es especialmente útil cuando la variable dependiente es binaria. También es útil cuando la variable dependiente es de medidas repetidas, ya que puede modelar la correlación. El presente estudio utilizó la simulación de Monte Carlo a fin de analizar las tasas de error de Tipo I empíricas de los GLMM en diseños split-plot. Las variables manipuladas fueron el tamaño de muestra, el tamaño de grupo, el número de medidas repetidas y la correlación entre las medidas repetidas. También se consideraron condiciones extremas, tales como muestras pequeñas, grupos no balanceados y diferente correlación en cada grupo (emparejamiento entre tamaño de grupo y correlación entre medidas repetidas). Para grupos balanceados, los resultados mostraron que el efecto grupo era robusto en todas las condiciones, mientras que para grupos no balanceados el efecto tendía a ser conservador con emparejamiento positivo y liberal con emparejamiento negativo. Con respecto a los efectos tiempo e interacción, los resultados mostraron, tanto para grupos balanceados como para no balanceados, que: (a) la prueba fue robusta con baja correlación (.2), ​​pero conservadora para valores medios de correlación (.4 y .6), y (b) la prueba tendía a ser conservadora para emparejamiento positivo y negativo, especialmente en este último.
NICE framework competency areas:
Authors: Wetzel Karen A
Published: June 2023

This publication from NICE describes Competency Areas as included in the Workforce Framework for Cybersecurity (NICE Framework), NIST Special Publication 800-181, Revision 1. The NICE Framework is a fundamental reference for describing and sharing information about cybersecurity work. At its core are Task, Knowledge, and Skill (TKS) statements that provide a foundation for learners, including students, job seekers, and employees. These statements are then used to define Competency Areas-clusters of related Knowledge and Skill statements that correlates with one's capability to perform Tasks in a particular domain-and Work Roles, which are composed of Task statements that constitute work for which someone is responsible or accountable. This document shares more detail about what NICE Framework Competency Areas are, including their evolution and development, clarifies the differences between Competency Areas and Work Roles, and provides example uses for Competency Areas from various stakeholder perspectives, and. Finally, the publication identifies where the NICE Framework list of Competency Areas is separately published and maintained distinct from this publication so it can be updated more frequently as a flexible and contemporary reference resource.
MONITORING AND CONTROL OF BASIC AIR QUALITY CONDITIONS INA UNIVERSITY EDUCATION FACILITY
Authors: MONTERO GUTIERREZ PAZ , CEREZO NARVAEZ ALBERTO , PASTOR  FERNANDEZ ANDRES , OTERO MATEO MANUEL , QUESADA SILVA PABLO
Published: June 2023

Carbon dioxide concentration, temperature and relative humidity in an indoor environment are some of the main indicators of indoor air quality (IAQ). In addition, these parameters are directly related to the airborne transmission of diseases. In this context, ventilation regulation is essential to balance safety via air renewal, with comfort and energy efficiency. In this research, an educational space of Faculty of Engineering is considered as a case study to control IAQ. To begin with, the weaknesses of the ventilation and air-conditioning systems are analysed and identified. Next, a low-cost device to monitor IAQ remotely is designed, developed and prototyped with a set of sensors and control elements. Then, the room is modelled and simulated by means of computational fluid dynamics (CFD), to select the location (placement/layout and quantity) of the sensors responsible for measuring the environmental parameters that characterise the IAQ. Finally, the wireless collected data are evaluated for interpretation, thanks to an Internet of Things (IoT) platform, in real time or deferred.

Key Words: Indoor air quality (IAQ), CO2 concentration, CFD simulation, sensor calibration, Internet of Things (IoT)
Improved (In-)Approximability Bounds for d-Scattered Set
Authors: Katsikarelis Ioannis , Lampis Michael , Paschos Vangelis
Published: June 2023

In the $d$-${\rm S{\small CATTERED}\;S{\small ET}}$ problem we are asked to select at least $k$ vertices of a given graph, so that the distance between any pair is at least $d$. We study the problem's (in-)approximability and offer improvements and extensions of known results for ${\rm I{\small NDEPENDENT}\;S{\small ET}}$, of which it is a generalization. Specifically, we show:

A lower bound of $\Delta^{\lfloor d/2\rfloor-\epsilon}$ on the approximation ratio of any polynomial-time algorithm for graphs of maximum degree $\Delta$ and an improved upper bound of $O(\Delta^{\lfloor d/2\rfloor})$ on the approximation ratio of any greedy scheme for this problem.
A polynomial-time $2\sqrt{n}$-approximation for bipartite graphs and even values of $d$, that matches the known lower bound by considering the only remaining case.
A lower bound on the complexity of any $\rho$-approximation algorithm of (roughly) $2^{\frac{n^{1-\epsilon}}{\rho d}}$ for even $d$ and $2^{\frac{n^{1-\epsilon}}{\rho(d+\rho)}}$ for odd $d$ (under the randomized ETH), complemented by $\rho$-approximation algorithms of running-times that (almost) match these bounds.
Morphing tree drawings in a small 3D grid
Authors: Arseneva Elena , Gangopadhyay Rahul , Istomina Aleksandra
Published: June 2023

We study crossing-free grid morphs for planar drawings of trees using the third dimension. A morph
consists of morphing steps,
where vertices of the tree move simultaneously along straight-line trajectories at constant speeds. The aim is to find a morph between two given drawings of the same tree that has a small number of steps and is crossing-free, i.e. no two vertices overlap or no two edges of the tree intersect except in their common endpoints at any moment during the morph. It is already known, that there exists a crossing-free morph between two drawings of an $n$-vertex planar graph $G$ with $\mathcal{O}(n)$ morphing steps, and that using the third dimension the number of steps can be reduced to $\mathcal{O}(\log n)$ for an $n$-vertex tree. However, these morphs do not bound one practical parameter, the resolution. Can the number of steps still be reduced substantially by using the third dimension with an additional restriction of keeping the resolution bounded throughout the morph? We answer this question in affirmative by presenting a $3D$ non-crossing morph between two planar grid drawings of an $n$-vertex tree in $\mathcal{O}(\sqrt{n} \log n)$ morphing steps such that each intermediate drawing is a grid drawing, i.e., vertices of the tree are mapped to the nodes of a $3D$ grid of polynomial volume.
La restitución: un remedio para la conquista de las Indias en el siglo XVI
Authors: Valdivia Jiménez Ramón Darío
Published: June 2023

El presente trabajo es una reflexión acerca del concepto de la restitución, como necesidad de seguridad ante una crisis moral, política y jurídica, centrada en el periodo de la conquista de América, y cuyo principal protagonista fue Bartolomé de Las Casas, pero también la “Escuela de Salamanca” y sus epígonos en Ultramar . La restitución nos habla, entonces y también hoy, no de re-escribir la historia, sino de ofrecer un sentido de justicia, y por tanto de orden. Superar la condición histórica de la in-justicia es el reto de los iusfilósofos de hoy, como lo fueron los del pasado.
Las lagunas normativas constitucionales: su integración mediante argumentos lógicos y cuasilógicos
Authors: Ibáñez Macías Antonio
Published: June 2023

El propósito de este trabajo es explorar las posibilidades de colmar las lagunas normativas constitucionales mediante el uso de argumentos lógicos y cuasilógicos. Para ello, se distingue entre lagunas aparentes y auténticas: las primeras se resuelven  mediante inferencias lógicas a partir de normas promulgadas (argumento lógico sistemático, argumento a contrario); en cambio, las lagunas auténticas no se pueden integrar mediante argumentos lógicos, sino, a lo sumo, mediante argumentos cuasilógicos (por analogía, a fortiori, a pari). Para el uso correcto de estos argumentos, se estudia, en general, qué enunciados jurídicos constitucionales pueden ser objeto de interpretación restrictiva y cuáles no.
Ética de la Inteligencia Artificial jurídica aplicada al proceso
Authors: De Asis Puido Miguel
Published: June 2023

En este trabajo se proponen una serie de principios éticos reguladores de la Inteligencia Artificial Jurídica aplicada al proceso judicial. Se comenzará con una introducción de la coyuntura social y tecnológica del momento. Tras ello, se hablará brevemente de los retos que plantea la Inteligencia Artificial Jurídica. El punto 3 se destinará a resumir el enfoque ético europeo respecto a esta tecnología, pasando luego a proponer siete principios ético-jurídicos que habrán de guiar el desarrollo de la Inteligencia Artificial Jurídica aplicada al proceso. En último lugar, se incidirá en la necesidad de un desarrollo legislativo de estos principios.
Dignidad humana e injusticia extrema. Un ejercicio de diálogo de tradiciones en la Filosofía del derecho
Authors: Chávez-Fernández Postigo José Carlos
Published: June 2023

Partiendo de la idea de «tradición» de MacIntyre y de la tesis de Alexy respecto de que existen concepciones de defensa o crítica de la razón práctica que pueden ser referidas principalmente a Aristóteles, Hobbes, Kant y Nietzsche, el objeto de este trabajo es explorar la posibilidad de un diálogo entre dichas tradiciones en orden a proponer vías razonables de solución para algunos problemas centrales de la Filosofía del derecho que se suscitan en el contexto de la discutida tesis de la conexión necesaria entre derecho y moral.  A partir de dos ejemplos estrechamente vinculados: el de la dignidad humana y el de la injusticia extrema, el autor planteará que dicho diálogo de tradiciones es posible. Pero, además, que el diálogo resulta enriquecedor si se encuentran razones suficientes para sostener la existencia y validez de algunos principios jurídicos indisponibles —razonablemente compatibles con la diversidad y la contingencia propia del derecho— sobre la base de una igual dignidad humana. El examen de estas tesis permitirá concluir también que el postpositivismo jurídico enfrenta semejantes o incluso mayores dificultades que el iusnaturalismo para su justificación, y plantear algunos interrogantes a las otras tradiciones.
Defensa Planetaria Integral. Un nuevo concepto de seguridad para el Antropoceno
Authors: Coronel Tarancón Alberto , Simó Soler Elisa , Peña Asensio Eloy
Published: June 2023

La entrada de las poblaciones humanas en el Antropoceno exige preguntarse qué significa la seguridad planetaria. En la intersección teórica de los estudios de Gaia, del Antropoceno y de Defensa Planetaria, proponemos un nuevo concepto de seguridad planetaria denominado Defensa Planetaria Integral, que comprende las amenazas ecológicas y las amenazas cósmicas desde un enfoque filosófico, jurídico y político coherente. Para ello, se argumenta la necesidad de superar, por un lado, el antropocentrismo de las estrategias de “seguridad humana”, y, por otro, el reduccionismo epistemológico de la defensa planetaria tradicional. Para ello se presenta, primero, el Antropoceno como un horizonte de pertenencia inédito, se analizan las principales amenazas ecológicas y cósmicas que afectan a la integridad de la biosfera, y, por último, se identifican los actores, los instrumentos y los antecedentes que pueden servir a los objetivos de la Defensa Planetaria Integral. De este modo, se inaugura un diálogo entre la filosofía, la ecología, la astrofísica y las ciencias jurídicas para la exploración de una nueva noción estratégica de seguridad planetaria.
Universalidad y efectividad de los derechos sociales: el acceso a las prestaciones sanitarias por migrantes en situación irregular
Authors: Arlettaz Fernando
Published: June 2023

El artículo aborda la evolución de regulación legal del derecho a las prestaciones sanitarias públicas por parte de migrantes en situación irregular. Se señala el pasaje de un régimen basado en el criterio de la residencia que permitía el acceso a esas prestaciones a uno basado en el criterio del aseguramiento que lo excluía (a partir de la reforma de 2012) y el regreso al régimen inicial (con la contra-reforma de 2018). Al mismo tiempo, se utiliza la regulación estudiada como punto de partida para reflexionar sobre los conceptos de universalidad y efectividad en relación con los derechos sociales.
Las acciones discriminatorias en el banquillo. Un estudio conceptual y de razonamiento probatorio
Authors: Giles Alejo Joaquín
Published: June 2023

Este trabajo se ocupa de la prueba de las acciones discriminatorias en dos dimensiones: la conceptual y la epistemológica. Se estructura en torno a dos preguntas. ¿En qué consiste, conceptualmente, una acción discriminatoria? Para abordar los problemas probatorios es necesario lograr claridad acerca de aquello que hay que probar. Una vez obtenida, se advertirá la importancia de trabajar sobre una segunda cuestión: ¿Cómo obtener creencias justificadas acerca de las intenciones y creencias ajenas? Exploraré dos estrategias argumentativas para hacerlo, buscando aumentar la nitidez con que comprendemos el problema que hay detrás del interrogante, así como nuestra habilidad para resolverlo.
Un horizonte jurídico para la Italian Theory
Authors: García López Daniel J.
Published: June 2023

Desde hace unos años se viene hablando de la Italian Theory como propuesta de una modernidad otra. Conceptos como bíos, communitas, immunitas, sacertas, imperium se sitúan en el centro del debate filosófico contemporáneo gracias a autores como Roberto Esposito, Giorgio Agamben o Toni Negri. Si bien se trata de un pensamiento heterogéneo, hay tres elementos que comparten: vida, historia y política. No obstante, hay una laguna que este artículo pretende colmar. Se trata de pensar la Italian Theory desde parámetros jurídicos. Se proponen las obras de Stefano Rodotà y Eligio Resta como ejemplos de esta corriente de pensamiento que nos abre una vía distinta a la hermenéutica, la deconstrucción o la filosofía analítica.
El nuevo mapa regulatorio del trabajo del hogar en España. Condicionantes político-jurídicos y condicionantes materiales de un sector precarizado y feminizado
Authors: Giménez Merino Antonio
Published: June 2023

El texto examina las luces y las sombras de la nueva normativa española sobre el empleo en el hogar en el contexto de la llamada «crisis de los cuidados». Para ello se examinan dos tipos de condicionantes que han influido en la reforma de 2022: los jurídico-internacionales y los político-sociales, donde destaca la autoorganización de las trabajadoras del sector. El estudio fija su atención en sus demandas, en diálogo con especialistas e instituciones, a fin de identificar con precisión los problemas a los que se enfrenta la reforma.
El desafío de la Inteligencia Artificial a la vigencia de los derechos fundamentales
Authors: Ester Sánchez Antonio Tirso
Published: June 2023

Es innegable que la Inteligencia Artificial está presente en nuestra vida cotidiana produciendo innumerables ventajas en el conjunto de la sociedad, aunque un uso indiscriminado de la IA conlleva riesgos que pueden afectar directamente a los derechos fundamentales de las personas. Este trabajo pretende analizar las implicaciones en los derechos fundamentales de los ciudadanos y los principios éticos que deben imperar en el uso de la IA, así como en los riesgos que conllevan, pero siendo conscientes que estamos ante una materia sobre la que existe aún más debate que derecho positivo.
Cultura de la cancelación, movimiento «woke», «tokenismo» y nueva sensibilidad: un análisis desde la filosofía jurídica, moral y política
Authors: García Cívico Jesús
Published: June 2023

Una vez se sitúan estos fenómenos como expresión de una tendencia sociocultural más amplia, que aquí llamamos tentativamente «nueva sensibilidad», se hacen evidentes las relaciones del fenómeno «woke» con transformaciones que guardan relación con el estado actual del debate entre reconocimiento y redistribución, con el «arte de la separación» y visiones complejas de la igualdad (las «esferas de la justicia» de Walzer), con la autonomía de los subsistemas sociales en los términos de Luhman o la distinción entre órdenes normativos propia de la Teoría del derecho. La corrección política, la relación entre derecho y moral, los límites a la libertad de expresión o la neocensura «difusa» son también parte del cambio cultural que afecta a temas de nuestro ámbito como la propia gestión de la diversidad cultural.
Squillacioti, Claudia. El matrimonio infantil: una cuestión de género. Causas subyacentes, consecuencias, configuraciones jurídicas y estrategias de erradicación, Cizur Menor: Thomson Reuters Aranzadi, 2021.
Authors: Meco Tébar Fabiola
Published: June 2023

Recensión de: Squillacioti, Claudia. El matrimonio infantil: una cuestión de género. Causas subyacentes, consecuencias, configuraciones jurídicas y estrategias de erradicación, Cizur Menor: Thomson Reuters Aranzadi, 2021.
MLL3 regulates the CDKN2A tumor suppressor locus in liver cancer
Authors: Zhu Changyu , Soto-Feliciano Yadira M , Morris John P , Huang Chun-Hao , Koche Richard P , Ho Yu-jui , Banito Ana , Chen Chun-Wei , Shroff Aditya , Tian Sha , Livshits Geulah , Chen Chi-Chao , Fennell Myles , Armstrong Scott A , Allis C David , Tschaharganeh Darjus F , Lowe Scott W
Published: June 2023

Mutations in genes encoding components of chromatin modifying and remodeling complexes are among the most frequently observed somatic events in human cancers. For example, missense and nonsense mutations targeting the mixed lineage leukemia family member 3 (MLL3, encoded by KMT2C) histone methyltransferase occur in a range of solid tumors, and heterozygous deletions encompassing KMT2C occur in a subset of aggressive leukemias. Although MLL3 loss can promote tumorigenesis in mice, the molecular targets and biological processes by which MLL3 suppresses tumorigenesis remain poorly characterized. Here, we combined genetic, epigenomic, and animal modeling approaches to demonstrate that one of the mechanisms by which MLL3 links chromatin remodeling to tumor suppression is by co-activating the Cdkn2a tumor suppressor locus. Disruption of Kmt2c cooperates with Myc overexpression in the development of murine hepatocellular carcinoma (HCC), in which MLL3 binding to the Cdkn2a locus is blunted, resulting in reduced H3K4 methylation and low expression levels of the locus-encoded tumor suppressors p16/Ink4a and p19/Arf. Conversely, elevated KMT2C expression increases its binding to the CDKN2A locus and co-activates gene transcription. Endogenous Kmt2c restoration reverses these chromatin and transcriptional effects and triggers Ink4a/Arf-dependent apoptosis. Underscoring the human relevance of this epistasis, we found that genomic alterations in KMT2C and CDKN2A were associated with similar transcriptional profiles in human HCC samples. These results collectively point to a new mechanism for disrupting CDKN2A activity during cancer development and, in doing so, link MLL3 to an established tumor suppressor network.
The CD73 immune checkpoint promotes tumor cell metabolic fitness
Authors: Allard David , Cousineau Isabelle , Ma Eric H , Allard Bertrand , Bareche Yacine , Fleury Hubert , Stagg John
Published: June 2023

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism, and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.
Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function
Authors: Mastwal Surjeet , Li Xinjian , Stowell Rianne , Manion Matthew , Zhang Wenyu , Kim Nam-Shik , Yoon Ki-jun , Song Hongjun , Ming Guo-li , Wang Kuan Hong
Published: June 2023

Dopamine system dysfunction is commonly implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive symptoms remain unresponsive to such pharmacological treatments and novel research paradigms investigating the circuit substrates underlying cognitive deficits are critically needed. The frontal cortex and its dopaminergic input from the midbrain are implicated in cognitive functions and undergo maturational changes during adolescence. Here, we used mice carrying mutations in the
Arc
or
DISC1
genes to model mesofrontal dopamine circuit deficiencies and test circuit-based neurostimulation strategies to restore cognitive functions. We found that in a memory-guided spatial navigation task, frontal cortical neurons were activated coordinately at the decision-making point in wild-type but not
Arc
mutant mice. Chemogenetic stimulation of midbrain dopamine neurons or optogenetic stimulation of frontal cortical dopamine axons in a limited adolescent period consistently reversed genetic defects in mesofrontal innervation, task-coordinated neuronal activity, and memory-guided decision-making at adulthood. Furthermore, adolescent stimulation of dopamine neurons also reversed the mesofrontal circuit and cognitive deficits in
DISC1
mutant mice. Our findings reveal common mesofrontal circuit alterations underlying the cognitive deficits caused by two different genes and demonstrate the feasibility of adolescent neurostimulation to reverse these circuit and behavioral deficits. These results may suggest developmental windows and circuit targets for treating cognitive deficits in neurodevelopmental disorders.
The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles
Authors: Ensinck Imke , Maman Alexander , Albihlal Waleed S , Lassandro Michelangelo , Salzano Giulia , Sideri Theodora , Howell Steven A , Calvani Enrica , Patel Harshil , Bushkin Guy , Ralser Markus , Snijders Ambrosius P , Skehel Mark , Casañal Ana , Schwartz Schraga , van Werven Folkert J
Published: June 2023

N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian MTC orthologues. Unlike the mammalian bipartite MTC, the yeast MTC is unipartite, yet multifunctional. The mRNA interacting module, comprising Ime4, Mum2, Vir1, and Kar4, exerts the MTC’s m6A-independent function, while Slz1 enables the MTC catalytic function in m6A deposition. Both functions are critical for meiotic progression. Kar4 also has a mechanistically separate role from the MTC during mating. The yeast MTC constituents play distinguishable m6A-dependent, MTC-dependent, and MTC-independent functions, highlighting their complexity and paving the path towards dissecting multi-layered MTC functions in mammals.
Mechanistic and evolutionary insights into isoform-specific ‘supercharging’ in DCLK family kinases
Authors: Venkat Aarya , Watterson Grace , Byrne Dominic P , O'Boyle Brady , Shrestha Safal , Gravel Nathan , Fairweather Emma E , Daly Leonard A , Bunn Claire , Yeung Wayland , Aggarwal Ishan , Katiyar Samiksha , Eyers Claire E , Eyers Patrick A , Kannan Natarajan
Published: June 2023

Catalytic signaling outputs of protein kinases are dynamically regulated by an array of structural mechanisms, including allosteric interactions mediated by intrinsically disordered segments flanking the conserved catalytic domain. The doublecortin-like kinases (DCLKs) are a family of microtubule-associated proteins characterized by a flexible C-terminal autoregulatory ‘tail’ segment that varies in length across the various human DCLK isoforms. However, the mechanism whereby these isoform-specific variations contribute to unique modes of autoregulation is not well understood. Here, we employ a combination of statistical sequence analysis, molecular dynamics simulations, and in vitro mutational analysis to define hallmarks of DCLK family evolutionary divergence, including analysis of splice variants within the DCLK1 sub-family, which arise through alternative codon usage and serve to ‘supercharge’ the inhibitory potential of the DCLK1 C-tail. We identify co-conserved motifs that readily distinguish DCLKs from all other calcium calmodulin kinases (CAMKs), and a ‘Swiss Army’ assembly of distinct motifs that tether the C-terminal tail to conserved ATP and substrate-binding regions of the catalytic domain to generate a scaffold for autoregulation through C-tail dynamics. Consistently, deletions and mutations that alter C-terminal tail length or interfere with co-conserved interactions within the catalytic domain alter intrinsic protein stability, nucleotide/inhibitor binding, and catalytic activity, suggesting isoform-specific regulation of activity through alternative splicing. Our studies provide a detailed framework for investigating kinome-wide regulation of catalytic output through cis-regulatory events mediated by intrinsically disordered segments, opening new avenues for the design of mechanistically divergent DCLK1 modulators, stabilizers, or degraders.
Five years later, with double the demographic data, naked mole-rat mortality rates continue to defy Gompertzian laws by not increasing with age
Authors: Ruby J. Graham , Smith Megan , Buffenstein Rochelle
Published: June 2023

The naked mole-rat (
Heterocephalus glaber
) is a mouse-sized rodent species, notable for its eusociality and long lifespan. Previously, we reported that demographic aging, i.e., the exponential increase of mortality hazard that accompanies advancing age in mammals and other organisms, does not occur in naked mole-rats (Ruby et al, 2018). The demographic data supporting that conclusion had taken over three decades to accumulate, starting with the original rearing of
H.glaber
in captivity. In the five years following that study, we ∼doubled our quantity of demographic data. Here, we re-evaluated our prior conclusions in light of these new data and found them to be supported and indeed strengthened. We additionally provided insight into the social dynamics of captive
H.glaber
with data and analyses of body weight and colony size versus mortality. Finally, we provide a phylogenetically-proximal comparator in the form of lifespan data from our Damaraland mole-rat (
Fukomys damarensis
) colony and demographic meta-analysis of those data along with published data from Ansell’s mole-rat (
Fukomys anselli
). We found
Fukomys
mortality hazard to increase gradually with age, an observation with implications on the evolution of exceptional lifespan among mole-rats and the ecological factors that may have accompanied that evolution.
Similaridades entre aglomerados produtivos: um ensaio teórico
Authors: Martiniano Mauricio Luiz Gonçalves , Junior Celso Machado , Silva Felipe Venancio , Lima Celimara Valente Gamba
Published: June 2023

Considerando o dinamismo do mundo atual, que rompeu as fronteiras organizacionais, identifica-se como desafio das micro e pequenas empresas a sua manutenção no mercado. Uma das estratégias de atuação das micro e pequena empresas está na criação de elos de cooperação na sua cadeia produtiva. Frente as limitações intrínsecas das micro e pequenas empresas, a cooperação é facilitada pela proximidade geográfica que estabeleça os aglomerados produtivos. Diante disso, este trabalho, no formato de ensaio teórico, se ocupou em fazer uma análise comparativa das conceituações dos principais aglomerados existentes, sejam eles: o Cluster, o Distrito Industrial e o Arranjo Produtivo Local, para, após o comparativo, ofertar distinções e semelhanças. O ensaio realizado se propõe a contribuir para o estudo da temática de aglomerados produtivos.
The Spectrum of Clinical Manifestations of Serious Human Parvovirus B19 Infection in Children without any Underlying DiseasesA Case Series
Authors: Bhattacharya Subham , Das Mrinal Kanti , Datta Supratim
Published: June 2023

Human Parvovirus B19 causes mild to life-threatening illnesses, especially in immunosuppressed individuals. In the immunocompetent individuals, the severe spectrum of clinical manifestations of the virus infection is not widely known. This case series presents the spectrum of clinical manifestations of serious Parvovirus B19 infection in children without any chronic haematological or immunodeficiency disease. This series is about a total of 12 children who were positive for Parvovirus Immunoglobulin M (IgM) antibody and the age range was between 1-12 years. Fever, fatigue, and arthritis were the most common manifestations. Pure red cell aplasia, the specific manifestation of Parvovirus infection, was seen only in one-third of patients. All the children were treated with Intravenous Immunoglobulin (IVIG) along with supportive therapy. All except one had a successful recovery.
Flood Vulnerability Assessment of Communities in Akwa Ibom, Nigeria
Authors: Agoha R. N. , Obafemi A. A. , Eludoyin O. S.
Published: June 2023

Floods are natural events, however, due to various anthropogenic activities coupled with climate change, flooding tends to be both human-induced and natural events. Geographical Information Systems (GIS) techniques can spatially process different physical-environmental parameters in flood risk assessment and the present study determine the extent of vulnerability among the communities in Akwa Ibom State, Nigeria. From the analysis, spatial extent of 932.26 km2 (13.48%) showed low flood vulnerability level while a spatial extent of 3411.37 km2 (49.33%) and 2572.09 km2 (37.19%) indicated moderate and high flood vulnerability levels respectively. At the Local Government Areas (LGAs) level, the low vulnerability covers 932.27 km2 which represented 13.48% of the entire LGAs in Akwa Ibom State, the medium vulnerability covers a spatial extent of 3411.37 km2 which represented 49.33% of the entire state while the high vulnerability covers a spatial extent of 2572.09 km2 which represented 37.19% of the LGAs in the state. The outcome further revealed that Two (2) LGAs are found within the low vulnerability, nineteen (19) LGAs are found within the medium vulnerability while ten (10) LGAs are found within the high vulnerability. At the community level, the analysis indicated that among the 795 communities in the state, 138 of the communities which represent 17.36% of the entire communities have low vulnerability to flood hazards, 429 communities at 53.96% have medium vulnerability level while 228 communities which represent 28.68% of the entire communities in the state have high flood vulnerability level. The generated maps and identified LGAs and communities at different flood vulnerability zones are useful in all steps of disaster management (prevention, mitigation, preparedness, operations, relief and recovery) and should be considered during initial planning.
Evaluation of Postharvest Chemical Treatment to Increase the Shelf Life of Guava L-49 and Allahabad Safeda Fruitsunder Ambient Storage
Authors: Rani Shalu , Kaur Parminder , Johar Vishal , Karthi J. S.
Published: June 2023

Physiologically mature, uniform fruits were thoroughly washed and dipped in aqueous solution of T0 (Untreated fruits), T1 (Boric acid at 200 ppm), T2 (Boric acid at 300 ppm), T3 (NAA at 100 ppm), T4 (NAA at 200 ppm), T5 (Salicylic acid at 300ppm), T6 (Salicylic acid at 400ppm) for five minutes. Fruits were placed in plastic trays and stored at ambient storage conditions for 12 days. The readings were observed after 4rd, 8th and 12th days. Physiological weight loss of fruits decreased with storage, further fruits treated with boric acid 300ppm recorded lower Physiological weight loss as compared to other treatments. Total Soluble Solids (TSS), Sugars were increased upto 12 days of storage.
Implementation Strategy of Port Clearance at UNTIA Fishing Port Makassar City, Indonesia
Authors: Amir Syamsul Marlin , Burhani Shidik
Published: June 2023

The contribution of Indonesia's fisheries sector in 2020 dropped by 0.63 percent compared to 2019, which grew to 6.24%. This shows that Indonesia's fisheries sector is facing problems, one of which is Illegal Unreported Unregulated Fishing (IUUF). The Ministry of Maritime Affairs and Fisheries of the Republic of Indonesia stated that state losses due to IUUF reached 300 trillion rupiah per year. Efforts to prevent IUUF in Indonesia have been made by controlling fishing management through licensing mechanisms, fisheries supervision, and followed up with law enforcement. One of the government instruments to prevent IUUF through licensing mechanism is by issuing Sailing Approval Letter/Port Clearance (PC) for fishing vessels. This study aims to formulate a strategy for the implementation of Sailing Approval Letter licensing for fishing vessels at Untia Fishing Port (UFP), Makassar City. This research is a quantitative research with survey method. Data were obtained from observations, questionnaires to measure fishermen's perceptions and attitudes, and structured interviews. Data analysis was conducted by quantitative analysis to measure the attitude and perception of fishermen; and SWOT analysis to determine strategies to improve the service process of issuing PC at UFP-Makassar City. Based on the results of the regulatory search, the PC licensing service at UFP-Makassar City refers to Law No. 11/2020, Law No. 45/2009, and Law No. 17/2008, Government Regulation No. 27/2021, KP Minister Regulation No.3/2013 and Minister of Transportation Regulation No.82/2014. The level of satisfaction of fishermen with PC services at UFP-Makassar City is 82.32% (performance category "Good"). The elements with the lowest level of satisfaction are Handling customer complaints, Speed of service, and Ability and skills of service officers. The results of the Internal Factor analysis Strategy (IFAS) and external Factor analysis Strategy (EFAS) show that the position of UFP Makassar City in an effort to improve of PC licence services is in quadrant II (stability). The strategies that must be carried out are (a) Increase the capacity of harbourmaster in the field of information system technology; and (b) collaborate and elaborate between UFP Makassar City, Provincial and City Fisheries Offices and Universities through policy studies to encourage fishing vessels to move in UFP-Makassar City in Indonesia.
Assessment of Demographic Changes of Workforce Diversity in Otolaryngology, 2013 to 2022
Authors: Fenton David , Hamzat Ibraheem , Dimitroyannis Rose , Nordgren Rachel , Saunders Milda R. , Baroody Fuad M. , Baird Brandon , Shogan Andrea
Published: June 2023

Importance

Given the growth of minoritized groups in the US and the widening racial and ethnic health disparities, improving diversity remains a proposed solution in the field of otolaryngology. Evaluating current trends in workforce diversity may highlight potential areas for improvement.

Objective

To understand the changes in gender, racial, and ethnic diversity in the otolaryngology workforce in comparison with changes in the general surgery and neurosurgery workforces from 2013 to 2022.

Design, Setting, and Participants

This cross-sectional study used publicly available data from the Accreditation Council for Graduate Medical Education and the Association of American Medical Colleges for 2013 to 2022, and included medical students and trainees in all US medical residency programs and allopathic medical schools.

Main Outcomes and Measures

Average percentages of women, Black, and Latino trainees during 2 intervals of 5 years (2013-2017 and 2018-2022). Pearson χ2 tests compared demographic information. Normalized ratios were calculated for each demographic group in medical school and residency. Piecewise linear regression assessed linear fit for representation across time periods and compared rates of change.

Results

The study population comprised 59 865 medical residents (43 931 [73.4%] women; 6203 [10.4%] Black and 9731 [16.2%] Latino individuals; age was not reported). The comparison between the 2 study intervals showed that the proportions of women, Black, and Latino trainees increased in otolaryngology (2.9%, 0.7%, and 1.6%, respectively), and decreased for Black trainees in both general surgery and neurosurgery (−0.4% and −1.0%, respectively). In comparison with their proportions in medical school, Latino trainees were well represented in general surgery, neurosurgery, and otolaryngology (normalized ratios [NRs]: 1.25, 1.06, and 0.96, respectively); however, women and Black trainees remained underrepresented in general surgery, neurosurgery, and otolaryngology (women NRs, 0.76, 0.33, and 0.68; Black NRs, 0.63, 0.61, and 0.29, respectively). The percentage of women, Black, and Latino trainees in otolaryngology all increased from 2020 to 2022 (2.5%, 1.1%, and 1.1%, respectively). Piecewise regression showed positive trends across all 3 specialties.

Conclusions and Relevance

The findings of this cross-sectional study indicate a positive direction but only a modest increase of diversity in otolaryngology, particularly in the context of national demographic data. Novel strategies should be pursued to supplement existing efforts to increase diversity in otolaryngology.
Mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with age‐related hearing loss
Authors: Miwa Toru , Katsuno Tatsuya , Wei Fan‐Yan , Tomizawa Kazuhito
Published: June 2023

Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification‐induced hearing loss and mitochondrial dysfunction.