bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivações para realizar práticas de cuidado na gestação de alto risco
Authors: Wilhelm Laís Antunes , Prates Lisie Alende , Alves Camila Neumaier , Scarton Juliane , Cremonese Luiza
Published: January 2021

Objetivo: conhecer as práticas de cuidado realizadas por gestantes de alto risco para preservar a gravidez e as motivações para realizá-las. Método: pesquisa qualitativa, realizada com dez mulheres que vivenciaram a gestação de alto risco. Os dados foram produzidos por meio de entrevista semiestruturada e submetidos à análise de conteúdo temática. A pesquisa seguiu os aspectos éticos, de acordo com as normas da resolução nº 466/12, sendo aprovada pelo parecer 222.320. Resultados: as motivações para as práticas de cuidado realizadas pelas gestantes visavam garantir a saúde do bebê e englobavam cuidados com a alimentação, o repouso e o afastamento de fatores estressantes. Eram práticas advindas de conhecimentos informais e profissionais. Conclusão: as gestantes de alto risco realizavam cuidados que envolviam demandas de diferentes esferas de necessidades e demonstravam necessidade de apoio emocional devido às mudanças ocorridas em sua rotina e no seu estilo de vida.
Tratamento interdisciplinar para reabilitação estética complexa do sorriso: relato de caso
Authors: Gondim André Luiz Marinho Falcão , Miyashita Eduardo , Sartori Ivete Aparecida de Mattias , Traina Andréia Aparecida , Neves Flávio Domingues das , Belo Horacio D’Aguiar Silva , Almeida Neto Luis Ferreira de , Marcelino Karolina Pires , Ferreira Ivalter José , Riesco Marta Gonzalez
Published: January 2021

Introdução: O planejamento prévio, se faz extremamente necessário antes de qualquer intervenção reabilitadora, e quando associado aos avanços tecnológicos, tornam os resultados clínicos mais seguros e estáveis. Com a utilização dos exames de imagens digitais, incluindo radiografias, tomografias e imagem de escaneamento intraoral ou de modelos, pode-se dispor de imagens tridimensionais de toda estrutura óssea e gengival, que associado a um protocolo fotográfico, modelos de estudo e enceramento diagnóstico, resultam num impacto decisivo na sequência clínica da reabilitação oral. Objetivo: Este trabalho tem como objetivo discutir um caso de reabilitação interdisciplinar e complexa do sorriso. Relato de Caso: Paciente com agenesia dos elementos dentários 32 e 42 que foi reabilitada com implantes e laminados cerâmicos, onde a partir do diagnóstico e planejamento interdiscilplinar, construiu-se uma sequência de etapas passando pela ortodontia, periodontia, implantodontia e prótese consecutivamente até a reabilitação final. Conclusão: Conclui-se que o anseio pelos resultados estéticos é cada vez maior e casos com graves defeitos estéticos na arquitetura óssea e gengival, tornam um desafio na reabilitação oral. Técnicas reconstrututivas aliadas ao planejamento e execução integrada de especialidades são a chave para o sucesso do tratamento de casos complexos. Grandes avanços no âmbito da tecnologia CAD/CAM, permitem executar a simulação virtual da reabilitação oral, tanto para as etapas cirúrgicas com a instalação de implantes osseointegráveis, como também para a reabilitação protética.
Formação farmacêutica com a inclusão de atuação educativa para promoção da saúde em escolas do município de Seropédica, Rio de Janeiro
Authors: Santos Jaqueline Rocha Borges dos , Silva Jéssica Cristina Correa da , Cruz Larrysa de Morais Alves da
Published: January 2021

O conceito de saúde extrapola a significância da ausência de doença, por estar relacionado com políticas públicas destinadas à compreensão de desenvolvimento e qualidade de vida da população. Este trabalho teve como objetivo realizar ações de promoção da saúde, conscientizando alunos, interligando os âmbitos de educação e saúde, mostrando a importância da formação farmacêutica para atuação educativa. O trabalho foi realizado através de atividades educativas em saúde para alunos (N=320) de uma escola do ensino infantil, fundamental e em duas escolas de ensino médio (N=100) no município de Seropédica. A atuação se deu por meio de palestras, com temas previamente definidos, de acordo com a demanda explicitada pela gestora da escola. Durante todas as palestras, os alunos demonstraram interesse interativo para compreender e aprender mais sobre os assuntos ministrados. A participação sinalizada por perguntas e aplicações ao cotidiano, garantiu a tônica na construção educativa, corroborando a proposta de prática e multiplicação do conhecimento adquirido. Os resultados observados confirmam a necessidade de formação do farmacêutico como educador em saúde, explicitando a importância nas ações de prevenção e promoção, melhorando a qualidade de vida da população através da educação.
Una revisión biográfica y significativa de las estructuras mixtas de hormigón y acero estructural
Authors: Serrano Corral Alvaro , Martínez Calzón Julio
Published: January 2021

El artículo plantea una revisión histórica y personal de la evolución de las estructuras mixtas en España vista por el autor que fue uno de los iniciadores de esta disciplina en España.

Se repasan los inicios de la disciplina, las principales referencias bibliográficas, las obras fundamentales del autor y aquellas innovaciones que se han llevado a cabo para mejorar el comportamiento estructural o los procesos constructivos.
Límites de esbeltez basados en prestaciones para vigas de hormigón armado para el control de deformaciones y el control de tensiones en la armadura
Authors: Marí Bernat Antonio , Torres Llinàs Lluís , Oller Ibars Eva , Barris Peña Cristina
Published: January 2021

Los procedimientos actuales de dimensionamiento a flexión de elementos de hormigón armado, basados ​​en la comprobación de estado límite último (ELU), proporcionan suficiente resistencia para soportar las cargas de diseño con un canto reducido. Sin embargo, las dimensiones estrictas de la sección transversal y la cantidad de armadura calculada para satisfacer el ELU pueden ser insuficientes para evitar deformaciones excesivas que pueden producir daños en los elementos no estructurales, o para garantizar el control de la fisuración y satisfacer así, los requisitos de durabilidad, funcionalidad o estética.Debido a la complejidad asociada a un cálculo riguroso de las deformaciones y el ancho de fisura en elementos de hormigón armado a lo largo de su vida útil, una forma efectiva de garantizar la satisfacción del estado límite de servicio es mediante la limitación de la relación de esbeltez l/d del elemento. En el presente estudio, el concepto de esbeltez límite, utilizado anteriormente para el control de la deformación, se generaliza para incorporar las limitaciones de la abertura de fisura, en el marco del diseño estructural basado en prestaciones. Por ello, se derivan las ecuaciones para la esbeltez límite que incorporan los parámetros principales que influyen en el comportamiento de servicio de los elementos de hormigón armado, que son válidos para secciones transversales rectangulares en forma de I o T y para elementos simplemente apoyados o continuos. La fisuración y los efectos a largo plazo se explican a través de coeficientes simplificados derivados de la mecánica estructural y las observaciones experimentales.Las esbelteces límite propuestas, tanto para una carga aplicada constante como para una deformación en la armadura constante, se comparan con las obtenidos utilizando el procedimiento EC2 para el cálculo de deformaciones, basado en la integración de curvaturas. Se han obtenido buenos resultados en términos de errores y dispersión, lo que demuestra que las esbelteces límite propuestas son una herramienta útil para el diseño basado en prestaciones de estructuras de hormigón armado. El carácter mecánico de la formulación facilita su modificación para situaciones diferentes a las utilizadas en su deducción, por ejemplo, diferentes tipos de carga, vigas parcialmente pretensadas o elementos de hormigón armado con FRP, entre otros.
Sobre la durabilidad estética en el diseño de puentes
Authors: Beade-Pereda Hector
Published: January 2021

El avance en el desarrollo de materiales y sistemas de construcción, así como en las técnicas de instrumentación y monitorización, ha hecho posible el plantearse el diseño, de manera sistemática, de puentes con una vida útil significativamente más larga que la que ha de considerarse en proyecto en la actualidad. Las conversaciones sobre puentes diseñados para 200 años son frecuentes en la actualidad, centrándose generalmente en aspectos como durabilidad, mantenimiento o predicción de uso futuro. Sin embargo, algo tan fundamental como cuál debe ser la apariencia de los puentes que se proyectan con una vida útil tan larga, suele obviarse en esos estudios.

Este artículo es una reflexión sobre cómo tener en cuenta consideraciones relativas a la apariencia en el diseño de estos puentes. Sobre qué parámetros hacen de un puente un elemento imperecederamente valioso en el entorno en el que se ubican. Sobre como alcanzar diseños cuya calidad percibida se transmite a lo largo de generaciones. Sobre durabilidad estética.

El artículo incluye un análisis cualitativo de una serie de puentes históricos, algunos de ellos construidos hace más de 200 años, con el objetivo de identificar qué los ha hecho exitosos (o no) desde un punto de vista formal, para así reflexionar sobre cómo aplicar lo aprendido al diseñar puentes con una vida útil extendida… y, por lo general, al diseñar cualquier puente (porque cien años son ya suficientes para hacer a la sociedad padecer un mal diseño).

La influencia en la durabilidad formal de un puente de conceptos como: tipo estructural, relación estructura-paisaje, ritmo y composición visual, esbeltez, espacio interior generado, simetría, memorabilidad, iconicidad, color, decoración, o moda en el momento de diseño, es analizada en este artículo.
Proyecto del nuevo puente arco de Alcántara sobre el río Tajo en la carretera EX-117 (Cáceres)
Authors: Sánchez de León Ramón Alfonso , Herrera Gómez Alberto , Sánchez de León Francisco
Published: January 2021

El puente romano de Alcántara soporta actualmente un importante tráfico rodado de vehículos pesados que circulan por la EX117 que está deteriorándolo considerablemente. Ante esta situación la Junta de Extremadura, a través de la Dirección General de Carreteras, convocó un concurso para la construcción de un nuevo puente.

La construcción de un puente paralelo al antiguo puente romano de Alcántara supone un fuerte reto para los ingenieros que sentimos el diseño de puentes como algo vocacional, no en vano,  dos mil  años de historia nos contemplan.  Después de pasar largas horas en el entorno del puente llegamos a la conclusión de que un arco de tablero superior,  encajado entre las dos laderas escarpadas del Tajo,  es la solución más natural y coherente, creando una perspectiva armónica con el entorno y en perfecta simbiosis con el puente romano.

Se ha buscado en el diseño del arco la sencillez y la elegancia, la pureza formal alejada de todo barroquismo y afectación, dentro de un orden clásico contrastado en el diseño de arcos. Se ha buscado el minimalismo y la austeridad para no  robar un ápice de protagonismo al puente romano.

Arco y tablero se diseñan como estructuras mixtas de acero y hormigón. El acero utilizado es acero de resistencia mejorada a la corrosión (acero corten) que adquiere una pátina de óxido que se integra perfectamente con el color de la oxidación férrica de las pizarras de la zona.

 

El puente principal con una longitud de 270,25 m que discurre sensiblemente paralelo al puente romano de Alcántara, constituido por un arco de principal de 180,00 metros de luz que salva el cauce ordinario del río Tajo y unos vanos de acompañamiento laterales: cinco vanos en la margen izquierda del río y un vano en la margen derecha.
Refuerzo de estructuras con morteros de ultra-alta resistencia, reforzados con fibras, en capa delgada
Authors: Madera Arroyo Pedro Ángel
Published: January 2021

Se presenta un sistema innovador para el refuerzo de elementos de hormigón, pilares, vigas y forjados, con morteros de ultra-alta resistencia armados en masa con fibras metálicas estructurales en capa delgada. El sistema permite reforzar pilares mediante recrecido de bajo espesor, vigas de hormigón a flexión y cortante, losas de hormigón armado, forjados reticulares y forjados unidireccionales de vigueta-bovedilla mediante la extensión, por la parte superior del forjado, de un mortero con alta resistencia a la tracción y elevadísima resistencia a la compresión, de forma que se obtiene una sección reforzada capaz de resistir mayores cargas tanto en zona de momentos positivos, debido al incremento del brazo de flexión, como en zona de momentos positivos, ya que el mortero soporta altas tensiones a tracción trabajando como una armadura de negativos adherida. Gracias a la formulación del mortero, que le confiere alta adherencia al soporte y retracción compensada, se consigue una sección monolítica sin necesidad de puentes de unión, conexiones al forjado ni mallazo de refuerzo adicional como se precisa en el refuerzo mediante recrecido de hormigón tradicional. Se presenta el sistema y los ensayos realizados que demuestran su idoneidad técnica para el fin perseguido.
Análisis numérico del proceso de fallo de una losa de hormigón armado con modelos de fractura no lineal
Authors: Ortega Parreño José Joaquín , Garijo Alonso Lucía , Ruiz López Gonzalo
Published: January 2021

El concurso “Cátedra ECSA”, organizado por la Universidad Politécnica de Valencia en 2018, planteaba estimar la carga máxima y el modo de rotura de una losa cuadrada de hormigón armado apoyada en cuatro puntos, con una carga central y otra en un vértice. Junto a este vértice se encontraba un orificio y los laterales correspondientes se reforzaban con un zuncho, aparte de los emparrillados superior e inferior. La losa real se ensayó tras la presentación de las soluciones de los participantes, resultando ganadora la más próxima al resultado experimental. Esta solución se alcanzó empleando un modelo de elementos finitos que considera el comportamiento cohesivo o cuasifrágil de la fractura del hormigón y la definición geométrica individual de las barras de armado, utilizando el programa comercial ATENA. El modelo permite seguir la evolución con la carga de la deformación de la losa, de la concentración de daño en el hormigón y el proceso de plastificación de las armaduras de acero. El resultado muestra el fallo de la losa por punzonamiento en los vértices contrarios al del orificio, protegido eficazmente por el zuncho. El fallo está controlado por la plastificación de la armadura inferior.
Heat Pipe as a Passive Cooling System Driving New Generation of Nuclear Power Plants
Authors: Nezam Ziba Zibandeh , Zohuri Bahman
Published: January 2021

The technology of the Heat Pipe (HP) system is very well known for scientists and engineers working in the field of thermal-hydraulic since its invention at Las Alamos Nation Laboratory around the 1960s time frame. It is a passive heat transfer/heat exchanger system that comes in the form of either a constant or variable system without any mechanical built-in moving part. This passive heat transfer system and its augmentation within the core of nuclear power reactors have been proposed in the past few decades. The sodium, potassium, or mercury type heat pipe system using any of these three elements for the cooling system has been considered by many manufacturers of fission reactors and recently fusion reactors particularly Magnetic Confinement Fusion (MCF). Integration of the heat pipes as passive cooling can be seen in a new generation of a nuclear power reactor system that is designed for unconventional application field such as a space-based vehicle for deep space or galaxy exploration, planetary surface-based power plants as well as operation in remote areas on Earth. With the new generation of Small Modular Reactor (SMR) in form of Nuclear Micro Reactors (NMR), this type of fission reactor has integrated Alkali metal heat pipes to a series of Stirling convertors or thermoelectric converters for power generation that would generate anywhere from 13kwt to 3Mwt thermal of power for the energy conversion system.
Does Blast Exposure to the Torso Cause a Blood Surge to the Brain?
Authors: Rubio Jose E. , Skotak Maciej , Alay Eren , Sundaramurthy Aravind , Subramaniam Dhananjay Radhakrishnan , Kote Vivek Bhaskar , Yeoh Stewart , Monson Kenneth , Chandra Namas , Unnikrishnan Ginu , Reifman Jaques
Published: January 2021

The interaction of explosion-induced blast waves with the torso is suspected to contribute to brain injury. In this indirect mechanism, the wave-torso interaction is assumed to generate a blood surge, which ultimately reaches and damages the brain. However, this hypothesis has not been comprehensively and systematically investigated, and the potential role, if any, of the indirect mechanism in causing brain injury remains unclear. In this interdisciplinary study, we performed experiments and developed mathematical models to address this knowledge gap. First, we conducted blast-wave exposures of Sprague-Dawley rats in a shock tube at incident overpressures of 70 and 130 kPa, where we measured carotid-artery and brain pressures while limiting exposure to the torso. Then, we developed three-dimensional (3-D) fluid-structure interaction (FSI) models of the neck and cerebral vasculature and, using the measured carotid-artery pressures, performed simulations to predict mass flow rates and wall shear stresses in the cerebral vasculature. Finally, we developed a 3-D finite element (FE) model of the brain and used the FSI-computed vasculature pressures to drive the FE model to quantify the blast-exposure effects in the brain tissue. The measurements from the torso-only exposure experiments revealed marginal increases in the peak carotid-artery overpressures (from 13.1 to 28.9 kPa). Yet, relative to the blast-free, normotensive condition, the FSI simulations for the blast exposures predicted increases in the peak mass flow rate of up to 255% at the base of the brain and increases in the wall shear stress of up to 289% on the cerebral vasculature. In contrast, our simulations suggest that the effect of the indirect mechanism on the brain-tissue-strain response is negligible (<1%). In summary, our analyses show that the indirect mechanism causes a sudden and abundant stream of blood to rapidly propagate from the torso through the neck to the cerebral vasculature. This blood surge causes a considerable increase in the wall shear stresses in the brain vasculature network, which may lead to functional and structural effects on the cerebral veins and arteries, ultimately leading to vascular pathology. In contrast, our findings do not support the notion of strain-induced brain-tissue damage due to the indirect mechanism.
Smoking, Vaping, and the Benefits Cessation in Times of COVID-19: A Public Health Perspective
Authors: Mungia Rahma , Valdez Danielle Nicole
Published: January 2021

The goal of this article is to inform dental practitioners and specialists of the benefits of smoking and vaping cessation in relation to COVID-19 transmission. COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has affected more than 31.7 million people globally with infection rates continuing to rise rapidly. Smoking dramatically impairs lung function and gives rise to an increase in susceptibility for infection, allowing for a more difficult recovery due, in part, to the damage SARS-CoV-2 does to the lungs. Tobacco smoking is one of the primary causes of death in the United States (US), however, nearly 40 million adults still smoke cigarettes, with 4.7 million middle and high school students using at least one tobacco product, including electronic cigarettes. COVID-19 is transmitted through salivary droplets, causing severe bilateral pneumonia and significantly reduced lung function, putting smokers and vapers at greater risk through cross-contamination and face touching. So far, data from animal studies suggest that vaping leads to an increased susceptibility to infection, which coincides with evidence of increased rates of chronic bronchitis in vapers. There is yet to be data regarding the benefits of smoking and vaping cessation during the COVID-19 pandemic. However, there is evidence suggesting that 4 weeks or more of smoking cessation intervention reduces the risk of contracting COVID-19 and developing severe complications. Because of these probable connections, dental practitioners should advise their patients to stop smoking and/or vaping via the 5 As Cessation Strategy.
Keep Safe, Keep Learning: Principals' Role in Creating Psychological Safety and Organizational Learning During the COVID-19 Pandemic
Authors: Weiner Jennie , Francois Chantal , Stone-Johnson Corrie , Childs Joshua
Published: January 2021

Utilizing a sample of 54 interviews from a larger study of traditional public school principals' responses to the COVID-19 pandemic, we examined the degree to which principals in 19 states and representing both urban (e.g., intensive, emergent or characteristic;n= 37) and suburban settings (n= 17) and across all student levels (i.e., elementary, middle, and high), experienced and engaged in behaviors to create psychological safety during the COVID-19 pandemic. We also sought to understand how various environmental and organizational features may have influenced these conditions and thus the likelihood of learning taking place. We find principals reported varied levels of psychological safety in their schools with associated differing levels of organizational learning and responsiveness to the crisis. However, rather being grounded in environmental conditions (e.g., urbanicity, demographics, etc.), organizational factors and specifically, differences in accountability, principal autonomy, professional culture and teacher decision-making were all key in the degree of psychological safety exhibited. Together, these findings serve to expand understanding of leadership as creating conditions for learning and give insight into the degree our pre-COVID-19 system may have facilitated or stymied the ability or capacity of school leaders in different settings to support transformational learning. In this way, this research may have real and important implications for the types of support leaders and teachers require as we collectively transition into the next phase of uncertainty as many schools continue to try and re-open safely and all that lays ahead.
Direct Methanation of Biogas—Technical Challenges and Recent Progress
Authors: Calbry-Muzyka Adelaide S. , Schildhauer Tilman J.
Published: January 2021

The direct methanation of biogas using hydrogen from electrolysis is a promising pathway for seasonal storage of renewables in the natural gas network. It offers particular advantages over the methanation of carbon dioxide separated from biogas, as it eliminates a costly and unnecessary carbon dioxide separation step. The key implementation challenges facing direct methanation of biogas are reviewed here: 1) treatment of biogas impurities; 2) competing reactor concepts for methanation; and 3) competing process concepts for final upgrading. For each of these three aspects, the state of the art is reviewed, focusing especially on results which have been validated at a high Technology Readiness Level (TRL) at recent long-duration demonstrations. The different technology solutions have advantages and disadvantages which may fit best to different technical and economic boundary conditions, which are discussed. As a final outlook, TRL 8 demo plants will be necessary to show the full potential of these systems, and to obtain consistent operation data to allow a cost comparison.
Analysis of Wild Type LbCpf1 Protein, and PAM Recognition Variants, in a Cellular Context
Authors: Shin Ujin , Brondani Vincent
Published: January 2021

Nucleases used in genome engineering induce hydrolysis of DNA phosphate backbone in a sequence-specific manner. So far CRISPR-Cas, the RNA-guided nucleases, is the most advanced genome engineering system. The CRISPR nucleases allows recognition of a particular genomic sequence with two distinct molecular interactions: first, by direct interaction between the nuclease and the protospacer-adjacent motif, wherein discrete amino acids interact with DNA base pairs; and second, by hybridization of the guide RNA with the target DNA sequence. Here we report the application of the single strand annealing cellular assay to analyze and quantify nuclease activity of wild type and mutant CRISPR-Cpf1. Using this heterologous marker system based on GFP activity, we observed a comparable PAM recognition selectivity with the NGS analysis. The heterologous marker system has revealed that LbCpf1 is a more specific nuclease than AsCpf1 in a cellular context. We controlled the in vitro activity of the Cpf1 nuclease complexes expressed in mammalian cells and demonstrated that they are responsible of the DNA cleavage at the target site. In addition, we generated and tested LbCpf1 variants with several combinations of mutations at the PAM-recognition positions G532, K538 and Y542. Finally, we showed that the results of the in vitro DNA cleavage assay with the wild type and mutants LbCpf1 corroborate with the selection of 6TG resistant cells associated to the genomic disruption of hprt gene.
Functional Characterization of Ly49+CD8 T-Cells in Both Normal Condition and During Anti-Viral Response
Authors: Shytikov Dmytro , Rohila Deepak , Li Dan , Wang Pengfei , Jiang Mei , Zhang Mingxu , Xu Qin , Lu Linrong
Published: January 2021

The role of Ly49+CD8 T-cells in the immune system is not clear. Previously, several papers suggested Ly49+CD8 T-cells as immunosuppressors, while multiple studies also suggested their role as potent participants of the immune response. The mechanism of Ly49 expression on CD8 T-cells is also not clear. We investigated phenotype, functions, and regulation of Ly49 expression on murine CD8 T-cells in both normal state and during LCMV infection. CD8 T-cells express different Ly49 receptors compared with NK-cells. In intact mice, Ly49+CD8 T-cells have a phenotype similar to resting central memory CD8 T-cells and do not show impaired proliferation and cytokine production. Conventional CD8 T-cells upregulate Ly49 receptors during TCR-induced stimulation, and IL-2, as well as IL-15, affect it. At the same time, Ly49+CD8 T-cells change the Ly49 expression profile dramatically upon re-stimulation downregulating inhibitory and upregulating activating Ly49 receptors. We observed the expression of Ly49 receptors on the virus-specific CD8 T-cells during LCMV infection, especially marked in the early stages, and participation of Ly49+CD8 T-cells in the anti-viral response. Thus, CD8 T-cells acquire Ly49 receptors during the T-cell activation and show dynamic regulation of Ly49 receptors during stimulation.
Exploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy
Authors: Qiu Qin , Lin Yuqi , Ma Yucui , Li Xiaoling , Liang Juan , Chen Zhiyan , Liu Kaifeng , Huang Yuge , Luo Hui , Huang Riming , Luo Lianxiang
Published: January 2021

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.
Tracheostomy in 80 COVID-19 Patients: A Multicenter, Retrospective, Observational Study
Authors: Tang Yun , Wu Yongran , Zhu Fangfang , Yang Xiaobo , Huang Chaolin , Hou Guo , Xu Wenhao , Hu Ming , Zhang Lu , Cheng Aiguo , Xu Zhengqin , Liu Boyi , Hu Song , Zhu Guochao , Fan Xuepeng , Zhang Xijing , Yang Yadong , Feng Huibin , Yu Lixia , Wang Bing , Li Zhiqiang , Peng Yong , Shen Zubo , Fu Shouzhi , Ouyang Yaqi , Xu Jiqian , Zou Xiaojing , Fang Minghao , Yu Zhui , Hu Bo , Shang You
Published: January 2021

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies.

Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days).

Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3–27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy.

Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.
Targeting the Malaria Parasite cGMP-Dependent Protein Kinase to Develop New Drugs
Authors: Baker David A. , Matralis Alexios N. , Osborne Simon A. , Large Jonathan M. , Penzo Maria
Published: January 2021

The single-celled apicomplexan parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria each year. The selection of drug resistance has been a recurring theme over the decades with each new drug that is developed. It is therefore crucial that future generations of drugs are explored to tackle this major public health problem. Cyclic GMP (cGMP) signaling is one of the biochemical pathways that is being explored as a potential target for new antimalarial drugs. It has been shown that this pathway is essential for all of the key developmental stages of the complex malaria parasite life cycle. This gives hope that targeting cGMP signaling might give rise to drugs that treat disease, block its transmission and even prevent the establishment of infection. Here we review previous work that has been carried out to develop and optimize inhibitors of the cGMP-dependent protein kinase (PKG) which is a critical regulator of the malaria parasite life cycle.
Paradigms of Protist/Bacteria Symbioses Affecting Human Health: Acanthamoeba species and Trichomonas vaginalis
Authors: Henriquez Fiona L. , Mooney Ronnie , Bandel Timothy , Giammarini Elisa , Zeroual Mohammed , Fiori Pier Luigi , Margarita Valentina , Rappelli Paola , Dessì Daniele
Published: January 2021

Ever since the publication of the seminal paper by Lynn Margulis in 1967 proposing the theory of the endosymbiotic origin of organelles, the study of the symbiotic relationships between unicellular eukaryotes and prokaryotes has received ever-growing attention by microbiologists and evolutionists alike. While the evolutionary significance of the endosymbiotic associations within protists has emerged and is intensively studied, the impact of these relationships on human health has been seldom taken into account. Microbial endosymbioses involving human eukaryotic pathogens are not common, and the sexually transmitted obligate parasite Trichomonas vaginalis and the free-living opportunistic pathogen Acanthamoeba represent two unique cases in this regard, to date. The reasons of this peculiarity for T. vaginalis and Acanthamoeba may be due to their lifestyles, characterized by bacteria-rich environments. However, this characteristic does not fully explain the reason why no bacterial endosymbiont has yet been detected in unicellular eukaryotic human pathogens other than in T. vaginalis and Acanthamoeba, albeit sparse and poorly investigated examples of morphological identification of bacteria-like microorganisms associated with Giardia and Entamoeba were reported in the past. In this review article we will present the body of experimental evidences revealing the profound effects of these examples of protist/bacteria symbiosis on the pathogenesis of the microbial species involved, and ultimately their impact on human health.
Solvent Accessibility of Residues Undergoing Pathogenic Variations in Humans: From Protein Structures to Protein Sequences
Authors: Savojardo Castrense , Manfredi Matteo , Martelli Pier Luigi , Casadio Rita
Published: January 2021

Solvent accessibility (SASA) is a key feature of proteins for determining their folding and stability. SASA is computed from protein structures with different algorithms, and from protein sequences with machine-learning based approaches trained on solved structures. Here we ask the question as to which extent solvent exposure of residues can be associated to the pathogenicity of the variation. By this, SASA of the wild-type residue acquires a role in the context of functional annotation of protein single-residue variations (SRVs). By mapping variations on a curated database of human protein structures, we found that residues targeted by disease related SRVs are less accessible to solvent than residues involved in polymorphisms. The disease association is not evenly distributed among the different residue types: SRVs targeting glycine, tryptophan, tyrosine, and cysteine are more frequently disease associated than others. For all residues, the proportion of disease related SRVs largely increases when the wild-type residue is buried and decreases when it is exposed. The extent of the increase depends on the residue type. With the aid of an in house developed predictor, based on a deep learning procedure and performing at the state-of-the-art, we are able to confirm the above tendency by analyzing a large data set of residues subjected to variations and occurring in some 12,494 human protein sequences still lacking three-dimensional structure (derived from HUMSAVAR). Our data support the notion that surface accessible area is a distinguished property of residues that undergo variation and that pathogenicity is more frequently associated to the buried property than to the exposed one.
Molecular Docking and Molecular Dynamics Aided Virtual Search of OliveNet™ Directory for Secoiridoids to Combat SARS-CoV-2 Infection and Associated Hyperinflammatory Responses
Authors: Thangavel Neelaveni , Al Bratty Mohammad , Al Hazmi Hassan Ahmad , Najmi Asim , Ali Alaqi Reem Othman
Published: January 2021

Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide (NNZ), and Nüzhenide (NZE) blocked the SARS-CoV-2 main protease (Mpro). Molecular dynamics (MD) simulation of the NZO-S-protein-ACE-2 complex by Desmond revealed stability during 50 ns. RMSD of the NZO-S-protein-ACE-2 complex converged at 2.1 Å after 20 ns. During MD, the interaction fractions confirmed multiple interactions of NZO with Lys417, a crucial residue for inhibition of S protein. MD of DMO-Mpro complex proved its stability as the RMSD converged at 1.6 Å. Analysis of interactions during MD confirmed the interaction of Cys145 of Mpro with DMO and, thus, its inhibition. The docking predicted IC50 of NZO and DMO was 11.58 and 6.44 μM, respectively. Molecular docking and dynamics of inhibition of the S protein and Mpro by NZO and DMO correlated well. Docking of the six-hit secoiridoids to IL1R, IL6R, and TNFR1, the receptors of inflammatory cytokines IL1β, IL6, and TNFα, revealed the anti-inflammatory potential except for DHO. Due to intricate structures, the secoiridoids violated Lipinski's rule of five. However, the drug scores of secoiridoids supported their use as drugs. The ADMET predictions implied that the secoiridoids are non-toxic and pose low oral absorption. Secoiridoids need further optimization and are a suitable lead for the discovery of anti-SARS-CoV-2 therapeutics. For the moment, olive secoiridoids presents an accessible mode of prevention and therapy of SARS-CoV-2 infection.
Neuroinflammation in Ischemic Stroke: Focus on MicroRNA-mediated Polarization of Microglia
Authors: Lian Lu , Zhang Yunsha , Liu Lu , Yang Liji , Cai Yichen , Zhang Junping , Xu Shixin
Published: January 2021

Ischemic stroke is one of the most common causes of death and disability worldwide. Neuroinflammation is a major pathological event involved in the process of ischemic injury and repair. In particular, microglia play a dual role in neuroinflammation. During the acute phase of stroke onset, M2 microglia are the dominant phenotype and exert protective effects on neuronal cells, whereas permanent M1 microglia contribute to prolonged inflammation and are detrimental to brain tissue. Emerging evidence indicates that microRNAs (miRNAs) may have regulatory effects on microglia-associated inflammation. Thus, we briefly reviewed the dynamic response of microglia after a stroke and assessed how specific miRNAs affect the behavior of reactive microglia. We concluded that miRNAs may be useful novel therapeutic targets to improve stroke outcomes and modulate neuroinflammation.
Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer?
Authors: Yu De-Yang , Bai Yan-Ling , Feng Yue , Wang Le , Yun Wei-Kang , Li Xin , Song Jia-Yu , Yang Shan-Shan , Zhang Yun-Yan
Published: January 2021

Background

To evaluate the dosimetric parameters of different bone marrow sparing strategies and radiotherapy technologies and determine the optimal strategy to reduce hematologic toxicity associated with concurrent chemoradiation (cCRT) for cervical cancer.

Methods

A total of 15 patients with Federation International of Gynecology and Obsterics (FIGO) Stage IIB cervical cancer treated with cCRT were re-planned for bone marrow (BM)-sparing plans. First, we determined the optimal BM sparing strategy for intensity modulated radiotherapy (IMRT), including a BMS-IMRT plan that used total BM sparing (IMRT-BM) as the dose-volume constraint, and another plan used os coxae (OC) and lumbosacral spine (LS) sparing (IMRT-LS+OC) to compare the plan without BM-sparing (IMRT-N). Then, we determined the optimal technology for the BMS-IMRT, including fixed-field IMRT (FF-IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). The conformity and homogeneity of PTV, exposure volume of OARs, and efficiency of radiation delivery were analyzed.

Results

Compared with the IMRT-N group, the average volume of BM that received ≥10, ≥20, ≥30, and ≥40 Gy decreased significantly in both two BM-sparing groups, especially in the IMRT-LS+OC group, meanwhile, two BMS-IMRT plans exhibited the similar effect on PTV coverage and other organs at risk (OARs) sparing. Among three common IMRT techniques in clinic, HT was significantly less effective than VMAT and FF-IMRT in the aspect of BM-Sparing. Additionally, VMAT exhibited more efficient radiation delivery.

Conclusion

We recommend the use of VMAT with OC and LS as separate dose-volume constraints in cervical cancer patients aiming at reducing hematologic toxicity associated with cCRT, especially in developing countries.
ACCELERATED CELL DEATH 6 Acts on Natural Leaf Senescence and Nitrogen Fluxes in Arabidopsis
Authors: Jasinski Sophie , Fabrissin Isabelle , Masson Amandine , Marmagne Anne , Lécureuil Alain , Bill Laurence , Chardon Fabien
Published: January 2021

As the last step of leaf development, senescence is a molecular process involving cell death mechanism. Leaf senescence is trigged by both internal age-dependent factors and environmental stresses. It must be tightly regulated for the plant to adopt a proper response to environmental variation and to allow the plant to recycle nutrients stored in senescing organs. However, little is known about factors that regulate both nutrients fluxes and plant senescence. Taking advantage of variation for natural leaf senescence between Arabidopsis thaliana accessions, Col-0 and Ct-1, we did a fine mapping of a quantitative trait loci for leaf senescence and identified ACCELERATED CELL DEATH 6 (ACD6) as the causal gene. Using two near-isogeneic lines, differing solely around the ACD6 locus, we showed that ACD6 regulates rosette growth, leaf chlorophyll content, as well as leaf nitrogen and carbon percentages. To unravel the role of ACD6 in N remobilization, the two isogenic lines and acd6 mutant were grown and labeled with 15N at the vegetative stage in order to determine 15N partitioning between plant organs at harvest. Results showed that N remobilization efficiency was significantly lower in all the genotypes with lower ACD6 activity irrespective of plant growth and productivity. Measurement of N uptake at vegetative and reproductive stages revealed that ACD6 did not modify N uptake efficiency but enhanced nitrogen translocation from root to silique. In this study, we have evidenced a new role of ACD6 in regulating both sequential and monocarpic senescences and disrupting the balance between N remobilization and N uptake that is required for a good seed filling.
Measurement of the Psychosocial Work Environment in Spanish: Validation of the Psychosocial Factors Questionnaire 75 (PSF-Q75) to Capture Demands and Resources at Different Levels of Analysis
Authors: Madrid Hector P. , Vasquez Cristian A. , Patterson Malcolm
Published: January 2021

The psychological work environment is composed of both stressful and motivational work conditions at different levels of analysis. However, most relevant theory and research lack an integrative conceptualization and appropriate instrumentation to account for this work context structure. These limitations are particularly present in non-mainstream populations, such as the Spanish community of researchers and practitioners. In this study, based on the job demands–resources model, we present an updated conceptualization in which stressful and motivational psychosocial factors are integrated and defined at the job, the group, and the organizational level of analysis into a single conceptualization. Furthermore, derived from this conceptualization, we present a study of the development and validation of a questionnaire to account for the psychosocial work environment in Spanish, labeled Psychosocial Factors Questionnaire 75 (PSF-Q75), which provides measures for 23 different psychosocial factors. The results of this study supported the questionnaire’s construct, convergent, divergent, and predictive validity, together with its reliability. Thus, this conceptualization and questionnaire provides researchers and partitioners with a more comprehensive approach to the assessment of the psychosocial work environment and promises benefits for interventions in the workplace.
Cross-Cultural Adaptation and Validation of the Physical Disability Resiliency Scale in a Sample of Chinese With Physical Disability
Authors: Duan Wenjie , Mu Wenlong , Xiong Hongxia
Published: January 2021

This study adapted the Physical Disability Resilience Scale (PDRS) to Chinese conditions and evaluated the psychometric characteristics of the Chinese version in individuals with physical disability. A total of 438 individuals with physical disability were included in this study. The PDRS was translated to Chinese using a backward translation method. Construct validity, internal consistency reliability, and convergent validity were examined. Confirmatory factor analysis failed to replicate the original five-factor structure of the PDRS. After removing the Spirituality factor and an underperformed item (Item 22), exploratory factor analysis yielded four trait factors (i.e., Emotional and Cognitive Strategies, Physical Activity and Diet, Peer Support, and Support from Family and Friends) and a method-effect factor. A correlated trait–correlated method model that included the four trait factors and a method-effect factor reported better model fit than the four-factor model, which did not consider method effects. The four subscales of the revised PDRS showed adequate internal consistency. The convergent validity of the revised PDRS was established by the moderate-to-strong associations between its four subscales and theoretically related constructs. We conclude that the revised PDRS is a reliable and valid measure in assessing resilience among Chinese people with physical disability.