bluuebunny/crossref_metadata_2025 huggingface dataset:
DE LA ECONOMÍA DE MERCADO A LA PLANIFICADA ESPECIAL REFERENCIA AL TURISMO
Authors: Escalona Francisco Muñoz
Published: March 2023

El sistema productivo de las economí­as avanzadas es, desde hace décadas, bimodal. Se compone de muy pocas empresas de gran tamaño y de numerosas empresas medianas y pequeñas. Mientras las primeras disfrutan de tanto poder de mercado que no dependen sustancialmente de él, las segundas han de adaptar su actividad a la mencionada institución. El turismo y sus sectores auxiliares han estado constituidos, tradicionalmente, por empresas pertenecientes al segundo grupo, pero desde hace varias décadas tanto las turoperadoras como algunas de las empresas paraturí­sticas (incentivadoras y facilitadoras) están pasando a formar parte del colectivo de grandes empresas. Este ensayo expone en primer lugar las caracterí­sticas de los sistemas de mercado y planificador para, finalmente, tomar en consideración la evolución de las empresas turí­sticas y paraturí­sticas hacia su inclusión en el grupo de grandes empresas.
O MARKETING DE LUGARES E A DINAMIZAÇÃO DO TURISMO PEDAGÓGICO: UM ESTUDO DE CASO
Authors: Machado Annaelise Fritz , Sousa Bruno Barbosa , Abreu Zilpa
Published: March 2023

O presente estudo procurou compreender o papel do marketing de lugares como alavanca do turismo segmentado numa lógica científica, acadêmica e de motivação pedagógica (em específico, as atividades turísticas realizadas no Resort Pedagógico Sítio do Carroção, Brasil).No que concerne à metodologia da pesquisa, após levantamento teórico em materiais sobre turismo, educação e turismo pedagógico foi realizado um estudo empírico de natureza exploratória no Resort Sítio do Carroção, com proposta de modelo conceitual.Como conclusões preliminares, importa referir que alguns destinos procuram posicionar a sua marca territorial numa clara tentativa de atrair novos visitantes e capitalizar esse segmento turístico. A gestão e o marketing de territórios, em específico o branding territorial, assume um papel determinante neste domínio, tanto ao nível da notoriedade da marca territorial (lembrança, memória e associação) como no que concerne à escolha e tomada de decisão por parte dos turistas e visitantes do turismo pedagógico. Contudo, e como limitações, este estudo apresenta como principal limitação a sua metodologia de natureza exclusivamente qualitativa. Estudos futuros deverão dar continuidade a este trabalho mediante metodologia de natureza quantitativa. Em específico, propõe-se a aplicação de inquéritos por questionário junto dos consumidores, testando um modelo conceitual em contextos de turismo pedagógico. O presente manuscrito representa uma importante contribuição para a área de estudo do turismo de nichos (ex.turismo pedagógico), que tem vindo a ser alvo de análises recentes no âmbito do marketing, uma vez que funciona como como uma chamada de atenção para a pertinência das questões ligadas ao processo ensino-aprendizagem em contextos turísticos.
CHUÍ/RS DIGITAL: ESTUDO EXPLORATÓRIO SOBRE A UTILIZAÇÃO DAS MÍDIAS SOCIAIS DIGITAIS NO SETOR HOTELEIRO
Authors: Bidarte Marcos Vinicius Dalagostini , Danielce Taiane Rodrigues , Acosta Lucimari Pereira
Published: March 2023

O marketing digital trouxe novas possibilidades de interação com os clientes, além de facilitar o processo de venda. Eles passam a ser o foco do marketing das empresas, exigindo novas formas de comunicação. Com o desenvolvimento das ferramentas tecnológicas surgiram as mí­dias sociais, que aparecem como novas formas de comunicação e relacionamento para a sociedade – e para as empresas. Nesse cenário, os meios de hospedagem precisam utilizar o marketing digital para a divulgação e valorização do empreendimento, mantendo o foco nos serviços oferecidos. Dada a importância do uso do marketing digital este estudo teve como objetivo verificar se os canais de distribuição online auxiliam na captação de clientes nos hotéis do municí­pio gaúcho do Chuí­-Brasil. Seguiu-se um percurso metodológico de caráter descritivo e exploratório, de abordagem quantitativa, sendo os dados coletados através da aplicação de questionário estruturado a sete de 10 empreendimentos hoteleiros, e analisados através de estatí­stica descritiva com auxí­lio teórico. Os principais resultados sinalizam que não há investimentos e nem exploração do potencial que as mí­dias sociais oferecem para promoção e divulgação dos empreendimentos, pois a maioria dos empreendimentos hoteleiros visa captar clientes somente através do Google+, Facebook e WhatsApp. Embora os meios de hospedagem do municí­pio gaúcho do Chuí­ visem a captação de clientes por meio das mí­dias sociais e tenham conhecimento da importância que elas apresentam para a divulgação e promoção dos empreendimentos, não são realizados investimentos na qualificação de pessoas e no setor de comunicação online, o que possibilitaria desenvolver uma gestão de marketing de relacionamento com os clientes.
EVALUACIÓN DEL BIENESTAR ANIMAL MEDIANTE COMPORTAMIENTOS SOCIALES Y PARÁMETROS PRODUCTIVOS EN CERDOS ALOJADOS EN SISTEMAS AL AIRE LIBRE Y EN CAMA PROFUNDA
Authors: Campagna Daniel Aldo , Dichio Luciana , Piazza Mila , Torres Patricia , Silva Patricia , Spinollo Luciano , Somenzini Diego , Mijoevich Ferderico , Larripa Marcelo
Published: March 2023

El objetivo de este trabajo fue evaluar la Riqueza Animal de un largo perí­odo en crecimiento-acabado a través de parámetros productivos y comportamientos positivos, en los sistemas productivos: Deep Bed (CP) y Free Aire (AL) en las estaciones del año. El lugar de realización fue el Módulo de Producción Porcina - Facultad de Ciencias Agrarias - UNR (Zavalla, Santa Fe- Argentina). Los animales de la etapa de crí­a con un peso vivo promedio (invierno = 28 ± 4 kg y verano = 24 ± 4 kg), se distribuyeron aleatoriamente entre los sistemas hijos: AL y CP (invierno -n: 36 AL, n: 36 CP- y verano -n: 65 AL, n: 65 CP). Para evaluar el bienestar animal se utilizaron indicadores recomendados por Welfare Quality ©, agrupados en parámetros de: Comportamiento social positivo (juzgar, investigar, reposo y otros -comiendo la bebida-) y parámetros productivos (Peso Final –PF- y Espesor de Grasa Dorsal - EDG). Estadí­sticamente, se utilizaron Análisis de Componentes Principales (PCA), Procedimientos de Permutación de Respuestas Múltiples (MRPP), estadí­stico Ï‡2 y prueba t de Student. Entre los comportamientos de ambos sistemas, se observó a partir de la prueba Ï‡2 que las diferencias entre los componentes fueron altamente significativas para verano (Ï‡2 = 127.62; gl = 3; p = 2.2x10-16) y para invierno (Ï‡2 = 19.037; gl = 3; p = 0,0003). A partir del test PCA y MANOVA se encontrarán diferencias significativas entre las estaciones del año (p <0,00020004), pero no entre sistemas (p <0,634927). Sin embargo, existe una diferencia significativa en la interacción (p <0.0954191), entre la época y el sistema. Los parámetros productivos, independientemente de la temporada, PF y EDG fueron significativamente mayores en CP (t = 2.437, p <0.017) y (t = 3.04407, p <0.003), respectivamente. Se concluye que los sistemas analizados brindan condiciones para el desarrollo de comportamientos sociales positivos (Bienestar animal). Sin embargo, en el sistema CP, más animales desarrollaron este tipo de comportamiento.
GRUPO DE ESTUDOS DA AGRICULTURA FAMILIAR GEAF-UFMG
Authors: Camargos Gustavo Henrique Silva , Lopes Luana Teixeira , Vieira Larissa Tiemi Matuzake , Borges Pedro Henrique Oliveira , Silva Brenda Letícia Leal dos Santos , Balloute Gabriel Rivetti Rocha , Sá Kelly dos Santos , Ramirez Matheus Anchieta
Published: March 2023

A Agricultura Familiar (AF) no Brasil representa a maioria das propriedades rurais e ocupa a maior parte da mão de obra agrí­cola, mas tem acesso marginal e oprimido à posse da terra. Neste sentido, o objetivo deste estudo de caso é apresentar as ações, resultados e impactos do "Grupo de Estudos da Agricultura Familiar da Escola de Veterinária da Universidade Federal de Minas Gerais (GEAF-UFMG)" . O GEAF-UFMG foi idealizado com o objetivo de realizar discussões e estabelecer trocas de informações acerca da AF. O grupo é composto por estudantes de graduação e pós-graduação de diversos cursos. Se configura como um espaço onde, por meio de encontros semanais, são organizados cursos, eventos, e outras atividades de extensão voltadas à atenção à AF. A partir do grupo de estudos, os estudantes têm oportunidade de aprofundar estudos na temática, promover politização, estabelecer ví­nculos com movimentos sociais e grupos que representam a AF, além de gerar habilidades e competências para o trabalho cooperado e em grupo.
La Dinámica de los Actores Sociales en el Uso de Organismos Genéticamente Modificados (OGM) en la Argentina
Authors: Walter Pablo Alberto
Published: March 2023

En los últimos decenios, en los sectores agrí­cola y alimentario, la ciencia y la tecnologí­a han impactado en todo el mundo por el uso de la biotecnologí­a moderna. Este trabajo busca de forma exploratoria y preliminar ver como los sujetos/organizaciones/representantes polí­ticos se articulan, relacionan en organismos y desenvuelven sus estrategias de participación en el contexto dado a partir del conocimiento y postura que tienen respecto al tema del uso de OGM. Se utilizó para interpretar una red multi-nodal de actores construyéndose mediante una matriz para analizar por la teorí­a de grafos, focalizado en los ví­nculos. En el trabajo se usó datos cualitativos más que cuantitativos y permitió visualizar, de forma preliminar, a los actores sociales, las interrelaciones y las vinculaciones que ayudan a la adopción, producción y venta de OGM en la Argentina. Este estudio da luz a la mirada de cómo los sujetos/organizaciones/representantes polí­ticos se articulan, relacionan en organismos y desenvuelven sus estrategias de participación en el contexto dado a partir del conocimiento y postura que tienen respecto al tema que convoca.
CARACTERIZACIÓN DE LOS MERCADOS DE EMPLEO EN EL SECTOR AGROPECUARIO ARGENTINO
Authors: Ghiglione Franco
Published: March 2023

El presente trabajo propone una discusión teórico-conceptual respecto de la conformación y consolidación de los mercados de empleo en el sector agropecuario argentino. Parte de dos enfoques que en cierta medida convergen en un contrapunto vinculado a los datos del objeto de análisis del artículo. Por un lado, se analiza un informe de la Federación Agropecuaria para el Desarrollo Argentino (FADA), quien realiza una estimación de la magnitud del mercado laboral agropecuario; por el otro, se analizan textos de distintos autores, quienes plantean un cuestionamiento a esta mirada tradicional y discursiva histórica de las organizaciones directamente vinculadas a los sectores de poder y la manipulación de las cifras que ellas realizan para ponderar al sector en cuestión. Seguidamente, se plantea una hipótesis personal que identifica un posible error en las perspectivas analizadas en el punto anterior y que tiene relación con el enfoque estático de la cuestión: los mercados laborales en el agro son dinámicos y están caracterizados por un elevado índice de estacionalidad de la demanda, por la cual lo correcto es profundizar en la comprensión de las características propias del mencionado proceso. Para ello, se analizaron diferentes artículos empíricos en función de marcos teóricos conceptuales contextualizados. Los resultados observados permitieron identificar, en forma preliminar, un elevado grado de informalidad y preponderancia del sector agroindustrial, comercial y servicios por sobre las actividades primarias.
INEFÁVEL FLUXO DA(S) CONSCIÊNCIA(S)
Authors: Araújo Joaquim Carlos Senos de
Published: March 2023

Trata-se de uma reflexão sobre o problema da definição do conceito de consciência e a sua possibilidade de se manifestar na mente animal, tentando compreender até que ponto as suas qualidades fenomenológicas são comunicáveis. Partindo de pressupostos neurológicos admitidos na ciência atual, estudaremos a consciência animal, forçosamente por analogia com a consciência humana. Recorrendo a exemplos encontrados em vários seres vivos, será debatida a tese do psiquismo zoológico, tentando encontrar a singularidade da consciência animal. Se a consciência pode ser caracterizada enquanto mecanismo biológico, logo o excede. Toda a consciência refere um sentimento primordial que se desenrola num fluxo temporal (tempo da consciência). É a fenomenologia que nos dará uma possível resposta.
FILOSOFIA COMO CONHECIMENTO ESSENCIAL PARA A FORMAÇÃO DO HOMEM
Authors: Vieira Ewerton Jesus
Published: March 2023

A perspectiva de formação do homem na filosofia de Sêneca contribui para o desenvolvimento do pensamento e da ação do indivíduo no sentido de possibilitar o acesso à ação prática da reflexão filosófica na vida cotidiana. A reflexão senequiana envolve a capacidade de buscar a vida feliz por meio da prática filosófica, ou seja, a busca pela felicidade consiste na aproximação do ser humano com o pensamento filosófico para assumir o projeto de uma vida digna. A filosofia apresenta condições de oferecer à pessoa o aperfeiçoamento da sua capacidade alusiva e reflexiva à realidade que nos circunda. O indivíduo ao encontrar no seu espaço cotidiano o sentido real das condições para a sua sobrevivência e, ao mesmo tempo, as respostas para o desenvolvimento do pensamento essencial para a formação humana.
CARTA DE DESCARTES A POLLOT
Authors: Coelho Rafael Teruel
Published: March 2023

Nesta breve carta endereçada a Pollot, pode-se ler a primeira menção de Descartes à Senhora Princesa da Boêmia, Elisabeth Simmern van Pallandt. Trata-se de um documento interessante, no qual o filósofo das ideias claras e distintas revela seu genuíno afeto por Elisabeth da Boêmia, sobretudo por ela ser uma princesa interessada por escritos de metafísica e, inclusive, por ter lido suas Meditações. Estamos diante do início de uma relação epistolar, filosófica e verdadeiramente amistosa, que irá perdurar até a morte de Descartes, o que se deu no ano de 1650, em Estocolmo.
ORÁCULO DE CRÁTILO E O SONHO DE SÓCRATES
Authors: Souza Luciano Ferreira de
Published: March 2023

O presente artigo tem como objetivo oferecer uma interpretação sobre o problema da chamada “correção dos nomes”, presente no diálogo Crátilo de Platão. Partindo da discussão entre Sócrates e seus interlocutores, Hermógenes e Crátilo, que aparentemente está apenas num âmbito linguístico, veremos como se dá a transição para o plano ontológico e epistemológico da questão dos nomes. Minha proposta de leitura, portanto, é mostrar como Platão faz surgir, a partir de cada uma das teses apresentadas, a sua própria teoria sobre a questão dos nomes.
AS ARTES E O ENSINO DE FILOSOFIA NO PRIMEIRO QUADRIÊNIO (2017-2021) DO PROF-FILO: BREVE ANÁLISE E ESTADO DA ARTE
Authors: Noyama Samon
Published: March 2023

Anais do “I Seminário de Ensino, Pesquisa e Extensão da Pós-Graduação em Filosofia da UNESAR”
A CRÍTICA DE LUDWIG WITTGENSTEIN À PSICOLOGIA NA DÉCADA DE 40
Authors: Almeida Yohana
Published: March 2023

Anais do “I Seminário de Ensino, Pesquisa e Extensão da Pós-Graduação em Filosofia da UNESAR”
LIBERDADE ASSISTIDA: UMA ANÁLISE DOS DOMÍNIOS SIMBÓLICOS DA SOCIOEDUCAÇÃO
Authors: Furtoso Gustavo , Vieira Godoy Elenilton
Published: March 2023

Anais do “I Seminário de Ensino, Pesquisa e Extensão da Pós-Graduação em Filosofia da UNESAR”
A TESTEMUNHA QUE NÃO SE PODE SUBORNAR: FOTOGRAFIA COMO ARMA DE GUERRA NAS TENSÕES INTERIMPERIAIS EM ÁFRICA (1903-1919)
Authors: Krachenski Naiara
Published: March 2023

Anais do “I Seminário de Ensino, Pesquisa e Extensão da Pós-Graduação em Filosofia da UNESAR”
INTERDISCIPLINARIDADE: A BNCC E O ENSINO DA LÍNGUA ESPANHOLA
Authors: Delong Silvia Regina
Published: March 2023

Anais do “I Seminário de Ensino, Pesquisa e Extensão da Pós-Graduação em Filosofia da UNESAR”
Mass spectrometry-based metabolomics for discovering active ingredients and exploring action mechanism of herbal medicine
Authors: Guo Sifan , Qiu Shi , Cai Ying , Wang Zhibo , Yang Qiang , Tang Songqi , Xie Yiqiang , Zhang Aihua
Published: March 2023

Natural products derived from herbal medicine are a fruitful source of lead compounds because of their structural diversity and potent bioactivities. However, despite the success of active compounds derived from herbal medicine in drug discovery, some approaches cannot effectively elucidate the overall effect and action mechanism due to their multi-component complexity. Fortunately, mass spectrometry-based metabolomics has been recognized as an effective strategy for revealing the effect and discovering active components, detailed molecular mechanisms, and multiple targets of natural products. Rapid identification of lead compounds and isolation of active components from natural products would facilitate new drug development. In this context, mass spectrometry-based metabolomics has established an integrated pharmacology framework for the discovery of bioactivity-correlated constituents, target identification, and the action mechanism of herbal medicine and natural products. High-throughput functional metabolomics techniques could be used to identify natural product structure, biological activity, efficacy mechanisms, and their mode of action on biological processes, assisting bioactive lead discovery, quality control, and accelerating discovery of novel drugs. These techniques are increasingly being developed in the era of big data and use scientific language to clarify the detailed action mechanism of herbal medicine. In this paper, the analytical characteristics and application fields of several commonly used mass spectrometers are introduced, and the application of mass spectrometry in the metabolomics of traditional Chinese medicines in recent years and its active components as well as mechanism of action are also discussed.
Oral microbiome correlates with selected clinical biomarkers in individuals with no significant systemic disease
Authors: Lim Mi Young , Kim Jung-Ha , Nam Young-Do
Published: March 2023

The oral microbiome is an important component of the microbiome in the human body. Although the association of the oral microbiome with various diseases, including periodontitis and cancer, has been reported, information on how the oral microbiome is related to health-related indicators in healthy populations is still insufficient. In this study, we examined the associations of the oral microbiome with 15 metabolic and 19 complete blood count (CBC)-based markers in 692 healthy Korean individuals. The richness of the oral microbiome was associated with four CBC markers and one metabolic marker. Compositional variation in the oral microbiome was significantly explained by four markers: fasting glucose, fasting insulin, white blood cell count, and total leukocyte count. Furthermore, we found that these biomarkers were associated with the relative abundances of numerous microbial genera, such as Treponema, TG5, and Tannerella. By identifying the relationship between the oral microbiome and clinical biomarkers in a healthy population, our study presents a direction for future studies on oral microbiome-based diagnosis and interventions.
Oral microbiome changes associated with the menstrual cycle in healthy young adult females
Authors: Yamazaki Ayaka , Ogura Kohei , Minami Kana , Ogai Kazuhiro , Horiguchi Tomomi , Okamoto Shigefumi , Mukai Kanae
Published: March 2023

The relationship between the menstrual cycle and the oral microbiome has not been clarified. The purpose of this study was to assess potential changes in the oral microbiome of healthy young adults using 16S rRNA-based sequencing. Eleven females (aged 23–36 years) with stable menstrual cycles and without any oral problems were recruited. Saliva samples were collected before brushing every morning during the menstrual period. Based on basal body temperatures, menstrual cycles were divided into four phases, namely the menstrual, follicular, early luteal, and late luteal phases. Our results showed that the follicular phase had a significantly higher abundance ratio of the Streptococcus genus than the early and late luteal phases, whereas the abundance ratios of the Prevotella 7 and Prevotella 6 genera were significantly lower in the follicular phase than those in the early and late luteal phases and that in the early luteal phase, respectively. Alpha diversity by the Simpson index was significantly lower in the follicular phase than that in the early luteal phase, and beta diversity showed significant differences among the four phases. Using the relative abundance data and copy numbers of the 16S rRNA genes in the samples, the bacterial amounts in the four phases were compared, and we observed that the follicular phase had significantly lower amounts of the Prevotella 7 and Prevotella 6 genera than the menstrual and early luteal phase, respectively. These results indicate reciprocal changes with the Streptococcus genus and Prevotella genera, particularly in the follicular phase. In the present study, we showed that the oral microbiome profiles are affected by the menstrual cycles of healthy young adult females.
Gut dysbiosis in autoimmune diseases: Association with mortality
Authors: Chang Sung-Ho , Choi Youngnim
Published: March 2023

To better understand the impact of gut dysbiosis on four autoimmune diseases [Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS)], this review investigated the altered gut bacteria in each disease and the shared ones among the four diseases. The enriched gut bacteria shared by three of the four autoimmune diseases were Streptococcus, Prevotella, and Eggerthella, which are associated with autoantibody production or activation of Th17 cells in immune-related diseases. On the other hand, Faecalibacterium comprises depleted gut bacteria shared by patients with SLE, MS, and SS, which is associated with various anti-inflammatory activities. The indexes of gut dysbiosis, defined as the number of altered gut bacterial taxa divided by the number of studies in SLE, MS, RA, and SS, were 1.7, 1.8, 0.7, and 1.3, respectively. Interestingly, these values presented a positive correlation trend with the standardized mortality rates —2.66, 2.89, 1.54, and 1.41, respectively. In addition, shared altered gut bacteria among the autoimmune diseases may correlate with the prevalence of polyautoimmunity in patients with SLE, SS, RA, and MS, that is, 41 percent, 32.6 percent, 14 percent, and 1–16.6 percent, respectively. Overall, this review suggests that gut dysbiosis in autoimmune diseases may be closely related to the failure of the gut immune system to maintain homeostasis.
Optimization design of crude oil distillation unit using bi-level surrogate model
Authors: Xiong Yingjian , Shi Xuhua , Ma Yongjian , Chen Yifan
Published: March 2023

Crude Oil Distillation Unit (CDU) is one of the most important separation installations in the petroleum refinery industries. In this work, a Bi-level Surrogate column model Aided Constrained Optimization Design (Bi-SACOD) is proposed for time-consuming objectives and constraints in the evolutionary optimization design of CDUs. The main components of Bi-SACOD include bi-level surrogate model construction (Bi-SMC), bi-level model management (Bi-MM), and particle swarm optimization (PSO) mixed-integer constrained evolutionary (PSO-MICE) search. Bi-SMC implements surrogate column model construction and feasible domain identification. Bi-MM combines surrogate column models with rigorous CDU simulations to perform model management, and PSO-MICE implements optimum search works. The optimization results of the CDUs indicate that Bi-SACOD outperforms the single-level surrogate column model approaches, and are more consistent with the rigorous CDU model optimization approach, whereas the evaluation numbers of the time-consuming rigorous models are significantly reduced.
Two new metazoans from the Cambrian Guanshan biota of China
Authors: Zhao Jun , Li Yujing , Selden Paul A.
Published: March 2023

Sessile epibenthos were diverse and played important part in the process of energy flow in the Cambrian marine ecosystem. Based on new specimens from the Gaoloufang Section of the Wulongqing Formation, we describe two new representatives of the group that show character traits with cnidarians and bryozoans. If confirmed, the new material can help us understand the origin and early evolution of these two phyla. The discovery of more sessile epibenthos suggests that the benthic ecosystem of the Guanshan biota (Cambrian Series 2, Stage 4) is more diverse than previously thought.
Phospholipase A and acyltransferase 4/retinoic acid receptor responder 3 at the intersection of tumor suppression and pathogen restriction
Authors: Zhao Jian-Yong , Yuan Xiang-Kun , Luo Rui-Zhen , Wang Li-Xin , Gu Wei , Yamane Daisuke , Feng Hui
Published: March 2023

Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since been referred to as ‘tazarotene-induced gene 3’ (TIG3) or ‘retinoic acid receptor responder 3’ (RARRES3) as a key downstream effector of retinoic acid signaling. Two decades of research have revealed the complexity of its function and regulatory roles in suppressing tumorigenesis. However, more recent findings have also identified PLAAT4 as a key anti-microbial effector enzyme acting downstream of interferon regulatory factor 1 (IRF1) and interferons (IFNs), favoring protection from virus and parasite infections. Unveiling the molecular mechanisms underlying its action may thus open new therapeutic avenues for the treatment of both cancer and infectious diseases. Herein, we aim to summarize a brief history of PLAAT4 discovery, its transcriptional regulation, and the potential mechanisms in tumor prevention and anti-pathogen defense, and discuss potential future directions of PLAAT4 research toward the development of therapeutic approaches targeting this enzyme with pleiotropic functions.
Rational strategies for enhancing mAb binding to SARS-CoV-2 variants through CDR diversification and antibody-escape prediction
Authors: Shah Masaud , Shin Ji-Yon , Woo Hyun Goo
Published: March 2023

Since the emergence of SARS-CoV-2, dozens of variants of interest and half a dozen variants of concern (VOCs) have been documented by the World Health Organization. The emergence of these VOCs due to the continuous evolution of the virus is a major concern for COVID-19 therapeutic antibodies and vaccines because they are designed to target prototype/previous strains and lose effectiveness against new VOCs. Therefore, there is a need for time- and cost-effective strategies to estimate the immune escape and redirect therapeutic antibodies against newly emerging variants. Here, we computationally predicted the neutralization escape of the SARS-CoV-2 Delta and Omicron variants against the mutational space of RBD-mAbs interfaces. Leveraging knowledge of the existing RBD-mAb interfaces and mutational space, we fine-tuned and redirected CT-p59 (Regdanvimab) and Etesevimab against the escaped variants through complementarity-determining regions (CDRs) diversification. We identified antibodies against the Omicron lineage BA.1 and BA.2 and Delta variants with comparable or better binding affinities to that of prototype Spike. This suggests that CDRs diversification by hotspot grafting, given an existing insight into the Ag-Abs interface, is an exquisite strategy to redirect antibodies against preselected epitopes and combat the neutralization escape of emerging SARS-CoV-2 variants.
A four-part guide to lung immunology: Invasion, inflammation, immunity, and intervention
Authors: Gopallawa Indiwari , Dehinwal Ruchika , Bhatia Vaibhav , Gujar Vikramsingh , Chirmule Narendra
Published: March 2023

Lungs are important respiratory organs primarily involved in gas exchange. Lungs interact directly with the environment and their primary function is affected by several inflammatory responses caused by allergens, inflammatory mediators, and pathogens, eventually leading to disease. The immune architecture of the lung consists of an extensive network of innate immune cells, which induce adaptive immune responses based on the nature of the pathogen(s). The balance of immune responses is critical for maintaining immune homeostasis in the lung. Infection by pathogens and physical or genetic dysregulation of immune homeostasis result in inflammatory diseases. These responses culminate in the production of a plethora of cytokines such as TSLP, IL-9, IL-25, and IL-33, which have been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Shifting the balance of Th1, Th2, Th9, and Th17 responses have been the targets of therapeutic interventions in the treatment of these diseases. Here, we have briefly reviewed the innate and adaptive i3mmune responses in the lung. Genetic and environmental factors, and infection are the major causes of dysregulation of various functions of the lung. We have elaborated on the impact of inflammatory and infectious diseases, advances in therapies, and drug delivery devices on this critical organ. Finally, we have provided a comprehensive compilation of different inflammatory and infectious diseases of the lungs and commented on the pros and cons of different inhalation devices for the management of lung diseases. The review is intended to provide a summary of the immunology of the lung, with an emphasis on drug and device development.
Machine learning-based identification of tumor-infiltrating immune cell-associated model with appealing implications in improving prognosis and immunotherapy response in bladder cancer patients
Authors: Chen Hualin , Yang Wenjie , Ji Zhigang
Published: March 2023

Background

Immune cells are crucial components of the tumor microenvironment (TME) and regulate cancer cell development. Nevertheless, the clinical implications of immune cell infiltration-related mRNAs for bladder cancer (BCa) are still unclear.

Methods

A 10-fold cross-validation framework with 101 combinations of 10 machine-learning algorithms was employed to develop a consensus immune cell infiltration-related signature (IRS). The predictive performance of IRS in terms of prognosis and immunotherapy was comprehensively evaluated.

Results

The IRS demonstrated high accuracy and stable performance in prognosis prediction across multiple datasets including TCGA-BLCA, eight independent GEO datasets, our in-house cohort (PUMCH_Uro), and thirteen immune checkpoint inhibitors (ICIs) cohorts. Additionally, IRS was superior to traditional clinicopathological features (e.g., stage and grade) and 94 published signatures. Furthermore, IRS was an independent risk factor for overall survival in TCGA-BLCA and several GEO datasets, and for recurrence-free survival in PUMCH_Uro. In the PUMCH_Uro cohort, patients in the high-IRS group were characterized by upregulated CD8A and PD-L1 and TME of inflamed and immunosuppressive phenotypes. As predicted, these patients should benefit from ICI therapy and chemotherapy. Furthermore, in the ICI cohorts, the high-IRS group was related to a favorable prognosis and responders have dramatically higher IRS compared to non-responders.

Conclusions

Generally, these indicators suggested the promising application of IRS in urological practices for the early identification of high-risk patients and potential candidates for ICI application to prolong the survival of individual BCa patients.
Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients
Authors: Körber Nina , Holzmann-Littig Christopher , Wilkens Gesa , Liao Bo-Hung , Werz Maia L. , Platen Louise , Cheng Cho-Chin , Tellenbach Myriam , Kappler Verena , Lehner Viktor , Mijočević Hrvoje , Christa Catharina , Assfalg Volker , Heemann Uwe , Schmaderer Christoph , Protzer Ulrike , Braunisch Matthias C. , Bauer Tanja , Renders Lutz
Published: March 2023

Background

Kidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens.

Method

We performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs.

Results

We detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19.

Conclusion

Our data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine–induced immune response in a transplant setting.
Integrated metabolomics and lipidomics analyses suggest the temperature-dependent lipid desaturation promotes aflatoxin biosynthesis in Aspergillus flavus
Authors: Wu Shaowen , Huang Wenjie , Wang Fenghua , Zou Xinlu , Li Xuan , Liu Chun-Ming , Zhang Wenyang , Yan Shijuan
Published: March 2023

Temperature is one of the main factors affecting aflatoxin (AF) biosynthesis in Aspergillus flavus. Previous studies showed that AF biosynthesis is elevated in A. flavus at temperatures between 28°C-30°C, while it is inhibited at temperatures above 30°C. However, little is known about the metabolic mechanism underlying temperature-regulated AF biosynthesis. In this study, we integrated metabolomic and lipidomic analyses to investigate the endogenous metabolism of A. flavus across 6 days of mycelia growth at 28°C (optimal AF production) and 37°C (no AF production). Results showed that both metabolite and lipid profiles were significantly altered at different temperatures. In particular, metabolites involved in carbohydrate and amino acid metabolism were up-regulated at 37°C on the second day but down-regulated from days three to six. Moreover, lipidomics and targeted fatty acids analyses of mycelia samples revealed a distinct pattern of lipid species and free fatty acids desaturation. High degrees of polyunsaturation of most lipid species at 28°C were positively correlated with AF production. These results provide new insights into the underlying metabolic changes in A. flavus under temperature stress.
Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis
Authors: Shi Hanqiang , Xiong Lie , Yan Guang , Du Shuqin , Liu Jie , Shi Yanbo
Published: March 2023

The clinical therapeutics of cervical cancer is limited due to the drug resistance and metastasis of tumor. As a novel target for antitumor therapy, ferroptosis is deemed to be more susceptible for those cancer cells with resistance to apoptosis and chemotherapy. Dihydroartemisinin (DHA), the primary active metabolites of artemisinin and its derivatives, has exhibited a variety of anticancer properties with low toxicity. However, the role of DHA and ferroptosis in cervical cancer remained unclear. Here, we showed that DHA could time-dependently and dose-dependently inhibit the proliferation of cervical cancer cells, which could be alleviated by the inhibitors of ferroptosis rather than apoptosis. Further investigation confirmed that DHA treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis. Among them, we unexpectedly found that heme oxygenase-1 (HO-1) played an antioxidant role in DHA-induced cell death. In addition, the results of synergy analysis showed that the combination of DHA and doxorubicin (DOX) emerged a highly synergistic lethal effect for cervical cancer cells, which was related also to ferroptosis. Overall, our data revealed the molecular mechanisms that DHA triggered ferritinophagy-dependent ferroptosis and sensitized to DOX in cervical cancer, which may provide novel avenues for future therapy development.
Neuronal biomolecular condensates and their implications in neurodegenerative diseases
Authors: Nam Jeongyeon , Gwon Youngdae
Published: March 2023

Biomolecular condensates are subcellular organizations where functionally related proteins and nucleic acids are assembled through liquid–liquid phase separation, allowing them to develop on a larger scale without a membrane. However, biomolecular condensates are highly vulnerable to disruptions from genetic risks and various factors inside and outside the cell and are strongly implicated in the pathogenesis of many neurodegenerative diseases. In addition to the classical view of the nucleation-polymerization process that triggers the protein aggregation from the misfolded seed, the pathologic transition of biomolecular condensates can also promote the aggregation of proteins found in the deposits of neurodegenerative diseases. Furthermore, it has been suggested that several protein or protein-RNA complexes located in the synapse and along the neuronal process are neuron-specific condensates displaying liquid-like properties. As their compositional and functional modifications play a crucial role in the context of neurodegeneration, further research is needed to fully understand the role of neuronal biomolecular condensates. In this article, we will discuss recent findings that explore the pivotal role of biomolecular condensates in the development of neuronal defects and neurodegeneration.
Robust and reusable self-organized locomotion of legged robots under adaptive physical and neural communications
Authors: Sun Tao , Dai Zhendong , Manoonpong Poramate
Published: March 2023

Introduction

Animals such as cattle can achieve versatile and elegant behaviors through automatic sensorimotor coordination. Their self-organized movements convey an impression of adaptability, robustness, and motor memory. However, the adaptive mechanisms underlying such natural abilities of these animals have not been completely realized in artificial legged systems.

Methods

Hence, we propose adaptive neural control that can mimic these abilities through adaptive physical and neural communications. The control algorithm consists of distributed local central pattern generator (CPG)-based neural circuits for generating basic leg movements, an adaptive sensory feedback mechanism for generating self-organized phase relationships among the local CPG circuits, and an adaptive neural coupling mechanism for transferring and storing the formed phase relationships (a gait pattern) into the neural structure. The adaptive neural control was evaluated in experiments using a quadruped robot.

Results

The adaptive neural control enabled the robot to 1) rapidly and automatically form its gait (i.e., self-organized locomotion) within a few seconds, 2) memorize the gait for later recovery, and 3) robustly walk, even when a sensory feedback malfunction occurs. It also enabled maneuverability, with the robot being able to change its walking speed and direction. Moreover, implementing adaptive physical and neural communications provided an opportunity for understanding the mechanism of motor memory formation.

Discussion

Overall, this study demonstrates that the integration of the two forms of communications through adaptive neural control is a powerful way to achieve robust and reusable self-organized locomotion in legged robots.
Predictors of deep-vein thrombosis for acute stroke at admission to a rehabilitation unit: A retrospective study
Authors: Li Fang , Wei Changkun , Huo Su , Liu Xiuzhen , Du Jubao
Published: March 2023

Background

Deep-vein thrombosis (DVT) is a common complication of acute stroke (AS). Only limited studies have discussed DVT in patients with AS at admission to a rehabilitation unit. The purpose of this study is to identify the predictors of DVT in AS patients admitted to a rehabilitation unit in China.

Methods

We retrospectively reviewed the medical records of all patients with AS admitted within 14 days of stroke onset between July 2019 and June 2022 at the Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, China. Ultrasonography was used to diagnose DVT in all patients within 3 days after rehabilitation admission. Univariate and binary logistic regression analyses were performed to determine the risk factors for DVT.

Results

Overall, 234 cases were identified and the incidence rate of DVT among AS patients was 13.2% (31/234). The univariate analysis showed that age, drinking, lower limb muscle strength, Brunnstrom Assessment (BRS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Barthel Index (BI) scale, serum albumin (Alb), and D-dimer were statistically significant factors. Age (OR = 1.037, 95% CI = 1.000–1.075, p < 0.05), BBS (OR = 0.952, 95% CI = 0.913–0.993, p < 0.05), and D-dimer (OR = 1.446, 95% CI = 1.130–1.849, p < 0.05) were demonstrated as independent risk factors for DVT.

Conclusion

Older age, lower BBS, and higher D-dimer levels at rehabilitation admission were independent risk factors for DVT. Therefore, ultrasonography should be performed for those patients with these three significant factors before implementing rehabilitation therapy.
Related consistent lures increase the judgment of multiplication facts: Evidence using event-related potential technique
Authors: Pan Yun , Shen Ji , Chen Lijuan , Jia Liangzhi , Tu Weiyu , Yang Huanyu
Published: March 2023

Simple multiplication errors are primarily shown in whether the lures are related to the operands (relatedness, such as 3 × 4 = 15 vs. 17) or whether the same decades are shared with the correct answers (consistency, such as 3 × 4 = 16 vs. 21). This study used a delayed verification paradigm and event-related potential technique to investigate the effects of relatedness and consistency in simple multiplication mental arithmetic for 30 college students in an experiment of presenting probes in auditory channels. We found that, compared to the related inconsistent lures, the related consistent lures showed significantly faster reaction time and induced significantly large amplitudes of N400 and late positive component. The findings suggest that related consistent lures are less affected by the activation diffusion of the arithmetic problem, and the credibility of being perceived as the correct answer is less; the lures related to operands and sharing the same decades with the accurate results can promote the judgment of multiplication mental arithmetic, and the results support the Interacting Neighbors Model.
Genetic disorders of neurotransmitter release machinery
Authors: Uzay Burak , Kavalali Ege T.
Published: March 2023

Synaptic neurotransmitter release is an evolutionarily conserved process that mediates rapid information transfer between neurons as well as several peripheral tissues. Release of neurotransmitters are ensured by successive events such as synaptic vesicle docking and priming that prepare synaptic vesicles for rapid fusion. These events are orchestrated by interaction of different presynaptic proteins and are regulated by presynaptic calcium. Recent studies have identified various mutations in different components of neurotransmitter release machinery resulting in aberrant neurotransmitter release, which underlie a wide spectrum of psychiatric and neurological symptoms. Here, we review how these genetic alterations in different components of the core neurotransmitter release machinery affect the information transfer between neurons and how aberrant synaptic release affects nervous system function.
Higher serum selenium concentration is associated with lower risk of all-cause and cardiovascular mortality among individuals with chronic kidney disease: A population-based cohort study of NHANES
Authors: Zhu Daiwen , Zhong Qiang , Lin Tao , Song Turun
Published: March 2023

Background

Selenium is an essential nutrient and trace element required for human health and plays an important role in antioxidative and anti-inflammatory processes. However, the long-term impact of selenium levels on the health of patients with chronic kidney disease remains unclear.

Method

Participants in this study were 3,063 CKD adults from the Third National Health and Nutrition Examination Survey (NHANES 1999–2000, 2003–2004, and 2011–2018). The mortality status and the cause of death of the study participants were obtained from the National Death Index records. For all-cause and cardiovascular disease (CVD) mortality, the models employed to estimate hazard ratios (HRs) and 95% CI were Cox proportional hazard models and competing risk models, respectively.

Result

During the follow-up period, 884 deaths occurred, including 336 heart-disease-associated deaths. The median (IQR) concentration of serum selenium was 181.7 (156.1, 201.5) μg/L. After full adjustment, serum selenium levels were associated with a decreased risk of mortality in patients with CKD, including all-cause and CVD mortality (P < 0.001). The multivariate-adjusted HRs (95%CI) were 0.684 (0.549–0.852) for all-cause mortality (Ptrend < 0.001) and 0.513 (0.356–0.739) for CVD mortality (Ptrend < 0.001) when selenium concentrations were compared according to the extreme quartiles. Selenium levels are inversely associated with an increased risk of all-cause mortality and CVD mortality. Similar results were observed in subgroup and sensitivity analyses.

Conclusion

Higher serum selenium concentration was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD.