bluuebunny/crossref_metadata_2025 huggingface dataset:
KINERJA TANGGUNG JAWAB SOSIAL PERUSAHAAN DAN EFISIENSI INVESTASI
Authors: Anis Idrianita
Published: November 2021

Beberapa tahun terakhir ini terlihat peningkatan pesat dalam tanggung jawab sosial perusahaan (CSR). Makalah ini membahas hubungan langsung dan tidak langsung antara kinerja CSR dan efisiensi investasi. Dengan menggunakan perusahaan manufaktur yang terdaftar di Bursa Efek Indonesia periode 2013-2017, pengambilan sampel dilakukan dengan metode purposive sampling dan dianalisis dengan regresi berganda. Hasil pertama menunjukkan bahwa perusahaan dengan kinerja CSR tinggi berinvestasi dengan lebih efisien. Analisis dilanjutkan dengan membedakan dua alternatif situasi: underinvestment dan overinvestment. Berfokus pada perusahaan yang kurang berinvestasi, kami menemukan bahwa kinerja CSR meningkatkan tingkat investasi perusahaan melalui pengurangan asimetri informasi. Sebaliknya, untuk perusahaan yang berinvestasi berlebihan, kinerja CSR mengurangi kelebihan investasi melalui mitigasi masalah arus kas bebas. Secara keseluruhan, temuan ini menunjukkan peran CSR secara tidak langsung memperbaiki efisiensi investasi tingkat perusahaan dengan mengatasi masalah keagenan serta masalah asimetri informasi.Kata kunci: Tanggung Jawab Sosial Perusahaan, Efisiensi investasi, Biaya keagenan, Asimetri informasi.
EVOLUSI IMAJINASI DALAM PENCIPTAAN SENI DAN MITOS KEKUASAAN
Authors: Priyantoro Eko
Published: November 2021

Karya seni sering diasosiasikan dengan pencapaian intelejensi manusia untuk membentuk peradaban. Menurut keilmuan sejarah, alat-alat sederhana pada jaman batu hingga era postmodern adalah rentang waktu penciptaan seni. Manusia pada awalnya menciptakan seni sebagai alat bantu (teknis) saja. Seiring dengan perkembangan zaman dan kompleksitas kehidupan sosial manusia, makna seni berubah menjadi lebih luas. Seni menjadi instrumen untuk penggambaran simbol atau perwakilan ide. Manusia selalu hidup dalam imajinasi atau alam abstrak membutuhkan mitos untuk hidup bersosialisasi. Karya seni yang bertransformasi dari idelogi tertentu menjadi alat terkuat untuk membentuk opini. Persilangan antara segala bentuk seni dengan berbagai media selalu menjadi ujung tombak pertarungan politik. Oleh karenanya, memahami propaganda yang menggunakan seni sebagai media kampanye adalah kebutuhan utama, terlebih lagi bagi bidang keilmuan akademisi.
ANALISIS SEMIOTIKA IKLAN “SOBAT FREN”
Authors: Sadah Khozinatus
Published: November 2021

ABSTRAK

Iklan merupakan salah satu metode pemasaran di masyarakat. Seiring perkembangan zaman, masyarakat berlomba-lomba membuat iklan yang menarik agar dapat menarik minat konsumen untuk membeli produk yang dipasarkan. Salah satunya adalah PT Smartfren Telecom Tbk yang meluncurkan produk kartu seluler ‘Sobat Fren’ dengan tema ‘Nelpon Pakai Fren, Bayarnya Pakai Daun’. Iklan produk ini dinilai menarik karena mengusung tema yang tidak biasa, dengan model yang menyerupai orang telanjang dan mengenakan daun. Beberapa masyarakat menilai iklan ini memiliki gambar yang kurang mendidik, oleh karena itu diperlukan analisa semiotika agar pesan dalam iklan dapat dikaji secara ilmiah. Analisa semiotika yang digunakan adalah teori Barthes dan Sausure karena mampu menyajikan semiotika secara struktural dan disajikan dengan bahasa yang tepat. Adapun hasil yang didapat adalah bahwa iklan ‘Sobat Fren’ meminjam makna gratis dari gambar daun. Tulisan ‘Nelpon pakai Fren, Bayar Pakai Daun’ merupakan anchor yang mempertegas dari keunggulan produk yang banyak menawarkan fasilitas telpon gratis. Tulisan ‘Sobat Fren’ menyugesti masyarakat bahwa produk kartu seluler tersebut bersahabat di masyarakat karena murah. Sedangkan ideologi yang dibangun adalah dengan menggunakan produk ‘Sobat Fren’ orang akan bahagia karena dapat menelfon secara gratis yang disimulasikan dengan gambar model pada iklan.

Kata kunci: iklan, Sobat Fren, semiotika, tanda 

 

ABSTRACT

Advertising is one of the marketing methods in the community. Along with the times, people are competing to make attractive advertisements in order to attract consumers to buy products that are marketed. One of them is PT Smartfren Telecom Tbk, which launched the mobile card product 'Sobat Fren' with the theme ‘Nelpon Pakai Fren, Bayarnya Pakai Daun’. This product advertisement is considered attractive because it carries an unusual theme, with a model that resembles a naked person and wears leaves. Some people consider this ad to have a less educating image, therefore a semiotic analysis is needed so that the message in the ad can be studied scientifically. Semiotic analysis used is the theory of Barthes and Sausure because it is able to present semiotics structurally and presented in an appropriate language. The results obtained are that the advertisement ' Sobat Fren' borrows free meanings from leaf drawings. The writing ‘Nelpon pakai Fren, Bayar Pakai Daun’ is an anchor that emphasizes the superiority of the products that offer many free telephone facilities. The article 'Sobat Fren' suggests the community that the cellular card product is friendly in the community because it is cheap. While the ideology that is built is to use the product 'Sobat Fren' people will be happy because they can call for free which is simulated with a model image on the ad.

Keywords: advertisement, Friend Fren, semiotics, sign
Conditional Noise Filter for MRI Images with Revised Theory on Second-order Histograms
Authors: Chan Wai Ti
Published: November 2021

Previous research by the author has the theory that histograms of second-order derivatives are capable of determining differences between pixels in MRI images for the purpose of noise reduction without having to refer to ground truth. However, the methodology of the previous research resulted in significant false negatives in determining which pixel is affected by noise. The theory has been revised in this article through the introduction of an additional Laplace curve, leading to comparisons between the histogram profile and two curves instead of just one. The revised theory is that differences between the first curve and the histogram profile and the differences between the second curve and the profile can determine which pixels are to be selected for filtering in order to improve image clarity while minimizing blurring. The revised theory is tested with a modified average filter versus a generic average filter, with PSNR and SSIM for scoring. The results show that for most of the sample MRI images, the theory of pixel selection is more reliable at higher levels of noise but not as reliable at preventing blurring at low levels of noise.
A Contactless Visitor Access Monitoring System
Authors: Bong Yi-Sin , Lee Gin-Chong
Published: November 2021

This project presents a contactless visitor access monitoring in small premises which implemented deep learning model in face recognition, develop the graphical user interface (GUI) for new visitor registration and visitor identification. Five stages of monitoring process are designed in the contactless visitor access monitoring (CVAM) GUI, the first step is to give instructions to the admin user regarding the monitoring process, the second step is to perform face recognition, the third step is to scan the body temperature, the fourth step is to perform mask detection on the visitor, and the final stage is to record visitor access time. Another visitor registration (VisReg) GUI is designed to register new visitors into the system. In VisReg, admin user is required to pre-process face images with MTCNN technique and generate new classifier with a ResNet pre-trained model. The contactless visitor access monitoring process is demonstrated. The face recognition gives an accuracy of 82%, while the mask detection gives an accuracy of 95% when tested with the validation dataset. It can be concluded that the visitor monitoring process can be carried out in a contactless way to eliminate the close contact between the security officers, receptionist, and visitors.
Nurses Perceptions of the Utilization of the Violence Assessment Tool (VAT) in Northeastern Ontario
Authors: Akpomi-Eferakeya Oghenefego (Fego) , Horrigan Judith , Heale Roberta , Donato Emily
Published: November 2021

Workplace violence (WPV) is an ongoing problem in health care. Most of the cases of WPV are caused by the patients, patients’ families, and friends. Violence in hospitals among registered nurses has led to 56% of lost time injuries, and in 2018, Ontario’s Workplace Safety and Insurance Board (WSIB) reported 13% of lost time injuries due to WPV. The Public Services Health and Safety Association (PSHSA) created the Violence Assessment Tool [VAT] to predict the possible risk of violence from patients in acute care settings. Health care workers can use the VAT to assess risk, apply possible control measures and improve their safety. As part of a larger study, the aim of this research is to explore nurses’ perceptions of the utilization of the VAT in assessing the potential risk of violence, and to identify any gaps, challenges, or improvements needed in the VAT. An Interpretive Description research design by Sally Thorne in (2016) will be used. The model that will guide this study is the Haddon Matrix framework of workplace violence prevention. The study will involve three focus groups via zoom virtual meetings with 6 to 8 participants per session, and an expected total of 18-24 participants. Focus group interviews will use semi-structured questions to guide the discussion among nurses working in a Northeastern Ontario hospital. Interpretive description data analysis will be guided by Thorne’s processes of data analysis. This will be the first study to examine nurses’ perceptions of the VAT in Ontario. The findings of this study will help to determine the predictive validity of the VAT and any potential changes that may be needed. The findings of this study could lead to reduced violence and associated costs within the healthcare sector.
Teorías relativas al error de prohibición y su aplicación en el Código Orgánico Integral Penal
Authors: Crespo-Cabrera Pedro
Published: November 2021

El artículo realizado consiste en un análisis pormenorizado referente al error de prohibición de carácter directo e indirecto con base y fundamento en las distintas teorías que definen y marcan su forma aplicación en el acontecer práctico del derecho penal en el Ecuador. Por lo mencionado este artículo, luego de definir las distintas teorías referentes al error de prohibición, consigue definir y especificar que teoría es la que se aplica según lo establecido en el Código Orgánico Integral Penal Ecuatoriano.
La importancia de esta investigación radica en que al dirimir que teoría es la aplicable en el Código Orgánico Integral Penal, se podrá conocer que elementos componen cada categoría dogmática del delito, entendiéndolo como acto, típico, antijurídico y culpable, diferenciando los elementos de pura objetividad de aquéllos que pueden ser susceptibles de valoraciones e interpretaciones, facilitando de esta manera la aplicación de la normativa mencionada a casos prácticos.
Crescimento e Desenvolvimento Inicial de Pitaya Branca (Hylocereus undatus) e Vermelha (Hylocereus monacanthus) no Município de Araguaína-TO
Authors: Panisson Deyson , Marques Nágila Kamille , Souza Filipe Bittencourt Machado de , Magri Neto José Caetano , Freire Ana Izabella , Araújo Nicolas Oliveira de , Melo Carlos Cicinato Vieira , Martins Athila Damasceno
Published: November 2021

A pitaya é uma fruta tropical pertencente à família Cactácea e originária da América Central e do Sul, que tem atraído pesquisadores e produtores pelo seu sabor e coloração. É uma fruta exótica e tornou-se uma fonte de renda para a agricultura familiar pois seus frutos possuem alto valor de mercado e a procura é crescente. O experimento foi instalado na área experimental do Centro Universitário Tocantinense Presidente Antônio Carlos (UNITPAC) município de Araguaína, Tocantins. O Objetivo do trabalho foi avaliar o crescimento e desenvolvimento inicial da pitaya vermelha e branca no município de Araguaína - TO. O delineamento utilizado foi em blocos casualizados e os tratamentos foram constituídos pelas duas cultivares, contendo cinco repetições. Utilizou-se clones das cultivares de pitaya vermelha e branca para a formação do pomar, no espaçamento de 2,5 x 1,5 m. As variáveis avaliadas foram: altura, diâmetro do caule e número de cladódios. Em relação ao diâmetro do caule, ambas as cultivares apresentaram um desempenho semelhante. Em relação ao número médio de cladódios por planta, ambas as espécies apresentaram quantidade de emissões de cladódios semelhantes, obtendo 15 cladódios em média por planta. A pitaya branca apresentou altura média de 1,91 m, enquanto que a pitaya vermelha, altura média de 1,93 m, após 11 meses da implantação. Ambos os clones apresentam um bom crescimento e desenvolvimento inicial nas condições edafoclimáticas no município de Araguaína-TO.
Caracterização química e funcional de polpa de Cubiu (Solanun sensiflorum Dunal) liofilizada para consumo em cápsulas
Authors: Oliveira Josiely da Silva de , Silva Rosane Silva da , Silva Marcos Túlio da
Published: November 2021

O cubiu (Solanum sessiliflorum Dunal) é um dos recursos genéticos nativos da Amazônia, bastante nutritivo, utilizado com diferentes propósitos – medicamento, alimento e cosmético. Assim, o objetivo desse trabalho foi liofilizar e encapsular a polpa de cubiu com a finalidade de averiguar a qualidade do produto através da realização de análises físico-químicas. Trata-se de um estudo experimental, sendo observadas as etapas do tratamento da polpa desde a liofilização até a encapsulação das amostras, a fim de se obter informações a respeito da influência da liofilização na forma de consumo e nas características físico-químicas e funcionais. Foram determinados análise centesimal da polpa com teores de umidade (90,25%), proteínas (0,87 %), lipídeos (1,92 %), cinzas (0,78 %), carboidratos (4,03%), o valor energético (33,88Kcal/100g) e pH (3,15). Na determinação da concentração do cubiu liofilizado, obteve teores de umidade (0,0%), proteínas (1,96 %), lipídeos (2,84 %), cinzas (1,45 %), fibras totais (4,86), carboidratos (11,11%), o valor energético (77,84Kcal/100g) a concentração de substâncias bioativas como pectina (2,64%), ácido ascórbico (11,86), compostos fenólicos (15,56), açúcares redutores (3,86), carotenoides totais (0,246). A maioria dos valores encontrados na determinação da composição da polpa apresenta-se dentro da faixa observada nas literaturas consultadas, normalmente referentes aos frutos produzidos na região Amazônica. O processo de liofilização demonstrou ser eficiente comparado com outros meios de desidratação e o método de encapsulação mostrou ser uma tecnologia com alto potencial podendo ser uma alternativa de grande importância, tanto na questão nutricional e funcional, como na questão logística.
A importância da alimentação na hipertrofia
Authors: Abreu Vitória Gomes , Lopes Rhaylla Sabina da Silva , Lima Eduarda Moreira , Santos Jânio Sousa
Published: November 2021

Alimentação adequada é um dos fatores determinantes para uma boa nutrição, qualidade de vida e melhora do desempenho físico. A busca por alimentação saudável e adequada está entre as prioridades de quem busca a hipertrofia muscular. Nesse sentido, o presente estudo tem o objetivo de verificar a importância da alimentação na hipertrofia, esclarecendo como obter melhora na musculatura e no ganho de massa corporal por meio da prática de exercícios físicos associadas a uma boa alimentação. O trabalho consiste em uma pesquisa bibliográfica, que trouxe dados da importância da alimentação e sua correlação com os treinos de hipertrofia. Como resultados, apresentou algumas dietas usuais; suplementos alimentares, como Whey protein, creatina e glutamina, utilizados para potencializar o desempenho em treinos e a alimentação adequada para a hipertrofia. Em destaque, ressalta-se carboidratos e proteínas como principais componentes alimentares, bem como a hidratação considerada um fator importante no processo. Mostrou ainda, que a quantidade de energia fornecida pelos alimentos, dependem da intensidade, duração e cronicidade do treino, não havendo um padrão que pode ser adotado por todos. Portanto, é necessário acompanhamento profissional de forma a prever a necessidade nutricional de cada pessoa, com base em seus objetivos desejados, promovendo assim, não somente a hipertrofia, mas manutenção e prevenção da saúde.
Perfil da mortalidade de mulheres na região Nordeste do Brasil em decorrência de depressão
Authors: Silva Maria Gabriela Pereira da , Camêlo Edwirde Luiz Silva , Aguiar Dalila Camêlo
Published: November 2021

Introdução: A depressão é um transtorno que afeta mais de 300 milhões de pessoas no mundo, contudo, o número de mulheres que apresentam esse transtorno é alarmante. Objetivo: Analisar o perfil de mulheres que morreram de alguma causa associada à depressão na região Nordeste do Brasil, entre 2014 a 2019. Métodos: Usamos uma tabela de contingência para apresentar um resumo das variáveis, matriz de correlação para identificação das relações e para reduzir a dimensionalidade sem perder informações e explicar essas variáveis em termos de suas componentes aplicamos a Análise de Componentes Principais. A coleta de dados foi realizada a partir dos dados do Sistema de Informação sobre Mortalidade (SIM), selecionando também a categoria do CID-10 que correspondem a episódios depressivos e transtorno depressivo recorrente (F32 e F33). As variáveis selecionadas foram raça, estado civil e escolaridade levando em consideração apenas pessoas do sexo feminino. Os dados foram tabulados no Excel e analisados no programa estatístico R versão 3.5.2. Resultados: Ocorreram 613 óbitos no sexo feminino nesse período, sendo principalmente mulheres pardas e casadas. As variáveis estão fortemente correlacionadas e hipóteses são levantadas: preconceito, vulnerabilidade social, falta de suporte social, relacionamento abusivo, mulheres procuram mais ajuda do que os homens. Conclusão: O perfil de mortalidade varia em função de raça e estado civil, sendo Bahia e Ceará os dois estados que obtiveram os índices mais significativos. Logo, se fazem necessárias políticas públicas, investimento na prevenção e promoção de qualidade de vida, rede de apoio a mulheres que passam por alguma situação que seja considerada fator de risco para um quadro depressivo.
Ácido linoleico na prevenção do infarto agudo do miocárdio: uma revisão integrativa
Authors: Araújo Gabrielle Guimarães , Souza Thaís Carolline Jesus , Flor Nicole Silva , Silva Alice Joana Souza Vieira da , Oliveira Tharcia Kiara Beserra de
Published: November 2021

Introdução: As doenças cardiovasculares, como o infarto agudo do miocárdio (IAM), são uma das principais causas de morte no Brasil e no mundo, afetando aproximadamente 183 para 100.000 habitantes. Se torna importante o controle da pressão arterial, e principalmente da dislipidemia observada na maioria dos pacientes através de dietas.  Objetivos: avaliar os efeitos do ácido linoleico na prevenção do infarto agudo do miocárdio. Metodologia: Esta é uma revisão abrangente da literatura, que revisa rigorosamente e combina pesquisas com diferentes métodos. Para seleção dos estudos, foi realizada uma leitura minuciosa dos títulos e dos resumos, a fim de verificar quais se encaixavam na questão norteadora e nos critérios de inclusão e exclusão. Resultados e discussão:  O ácido linoleico é um precursor do ácido araquidônico, que participa da síntese de mediadores biologicamente ativos, como prostaglandinas, tromboxanos e leucotrienos. Essas substâncias atuam como mediadores inflamatórios, estimulantes e cicatrizantes. Pacientes com infarto agudo do miocárdio (IAM) podem se beneficiar de suplementação ácidos graxos poliinsaturados. Conclusão: A ingestão dos ácidos graxos está relacionada com a diminuição do risco de paradas cardíacas, possuindo efeito regulador sobre as propriedades elétricas do miocárdio, reduzindo as arritmias ventriculares e o risco de morte súbita.
Effects of ambient temperature on dive behavior of East Pacific green turtles before and after a power plant closure
Authors: Madrak SV , Lewison RL , Eguchi T , Klimley AP , Seminoff JA
Published: November 2021

Water temperature plays a critical role in mediating energy budgets and influencing the behavior of marine ectotherms. Previous research has demonstrated that marine ectotherms such as sea turtles conserve energy by decreasing activity levels in colder water—often at or near the latitudinal limits of their range. San Diego Bay is near the northern edge of the range for eastern Pacific green turtles and is home to a year-round foraging population. Turtles in San Diego Bay experienced a significant decrease in ambient water temperature following the closure of a fossil-fuel-based power plant and corresponding loss of the plant’s warm-water effluent. Time-depth recorders were placed on 13 turtles before (n = 5) and after (n = 8) the closure of this plant to determine how changing water temperature influenced dive duration. Deployments lasted 2-25 d, with a mean deployment of 7.5 d. Green turtle behavior in different thermal regimes revealed a strong relationship between dive duration and water temperature; dive duration was significantly longer when water temperatures were colder, especially when water was below 14.4°C. Establishing the inactivity threshold for this population is critical to future management in light of temperature variability in coastal habitats and the impacts this may have on sea turtle energetics. Understanding organismal response to relatively rapid shifts in thermal conditions is relevant to assessments of the direct and indirect anthropogenic effects on aquatic environments.
From Constellations to Assemblages: Benjamin, Deleuze and the Question of Materialism
Authors: Prokić Tanja
Published: November 2021

This essay investigates the differences and points of contact between Walter Benjamin's concept of ‘constellation’ (developed in various texts written between 1920 and 1940) and the notion of ‘assemblage’ as theorised by Gilles Deleuze and Félix Guattari. Both concepts address the entanglement of discourse and matter, bodies and devices, and raise questions regarding the historicity and temporality of different kinds of multiplicity. Presently, the term ‘assemblage’ figures prominently in the context of the new materialism, a theoretical movement which calls for a renewal of materialist ideas, proposing a break with the historical materialism of the past. Against this backdrop, the essay has a twofold purpose: first, by focusing on the notions of constellation and assemblage, it seeks to highlight the differences and analogies between the materialisms of Benjamin, on the one hand, and Deleuze and Guattari, on the other. Second, by examining the new materialism's appropriation of Deleuzian ‘assemblage theory’, it will not only analyse what is ‘new’ about the new materialism, but also underline its conceptual errors and political problems. Eventually, what the essay argues is that our contemporary (‘new materialist’) understanding of assemblages might indeed benefit from a more thorough engagement with the historical materialism of an author like Benjamin.
Biocompatible Mesoporous Silica–Polydopamine Nanocomplexes as MR/Fluorescence Imaging Agent for Light-Activated Photothermal–Photodynamic Cancer Therapy In Vivo
Authors: Lu Jiahui , Ni Chen , Huang Jie , Liu Yawen , Tao Yingkai , Hu Pengcheng , Wang Yong , Zheng Shaohui , Shi Meilin
Published: November 2021

Conventional cancer phototherapy with single modality suffers from low therapeutic efficacy and undesired posttreatment damage for adjacent normal tissues. Therefore, the lower NIR laser irradiation power is vital to the reduction or preclusion of risk of scalds and burns in normal tissues. Herein, we rationally proposed a novel multifunctional nanocomplex, which enabled good magnetic resonance (MR) imaging contrast effect and promising photothermal conversion efficacy. The prepared core/shell nanocomplexes [MSN-Ce6@PDA (Mn)] were composed of chlorin e6-embedded mesoporous silica/nanoparticle composites as the cores, and then polydopamine and manganese ions were conjugated on the cores to form protective shells. The MSN-Ce6@PDA (Mn) nanocomplexes revealed superior properties in colloidal stability, photothermal conversion, reaction oxygen species generation, magnetic resonance imaging, etc. Under the guidance of MR and fluorescence imaging, these MSN-Ce6@PDA (Mn) nanocomplexes were found to be primarily accumulated in the MDA-MB-231 tumor area. Furthermore, the combined photodynamic and photothermal therapy exhibited strong inhibition to the growth of MDA-MB-231 tumor in vitro and in vivo. Besides, the MSN-Ce6@PDA (Mn) nanocomplexes also exhibited excellent biocompatibility and low damage to the healthy animals. Hence, the results demonstrated that the prepared MSN-Ce6@PDA (Mn) nanocomplex would be a promising potential for multimodal imaging-guided phototherapy.
Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering
Authors: Hao Zhuowen , Xu Zhenhua , Wang Xuan , Wang Yi , Li Hanke , Chen Tianhong , Hu Yingkun , Chen Renxin , Huang Kegang , Chen Chao , Li Jingfeng
Published: November 2021

The repair of critical bone defects remains challenging worldwide. Three canonical pillars (biomaterial scaffolds, bioactive molecules, and stem cells) of bone tissue engineering have been widely used for bone regeneration in separate or combined strategies, but the delivery of bioactive molecules has several obvious drawbacks. Biophysical stimuli have great potential to become the fourth pillar of bone tissue engineering, which can be categorized into three groups depending on their physical properties: internal structural stimuli, external mechanical stimuli, and electromagnetic stimuli. In this review, distinctive biophysical stimuli coupled with their osteoinductive windows or parameters are initially presented to induce the osteogenesis of mesenchymal stem cells (MSCs). Then, osteoinductive mechanisms of biophysical transduction (a combination of mechanotransduction and electrocoupling) are reviewed to direct the osteogenic differentiation of MSCs. These mechanisms include biophysical sensing, transmission, and regulation. Furthermore, distinctive application strategies of biophysical stimuli are presented for bone tissue engineering, including predesigned biomaterials, tissue-engineered bone grafts, and postoperative biophysical stimuli loading strategies. Finally, ongoing challenges and future perspectives are discussed.
Altered Lipid Profiles and Vaccine Induced-Humoral Responses in Children Living With HIV on Antiretroviral Therapy in Tanzania
Authors: Mbuya Wilbert , Mwakyula Issakwisa , Olomi Willyelimina , Agrea Peter , Nicoli Francesco , Ngatunga Cecilia , Mujwahuzi Leodegard , Mwanyika Paul , Chachage Mkunde
Published: November 2021

People living with HIV, even under therapy, have a high burden of age-related co-morbidities including an increased risk of dyslipidemia (which often predisposes to cardiovascular diseases) and immune-aging. In this study, lipid profiles and antibody responses to measles and pertussis toxin vaccines were compared between ART experienced HIV+ children (n=64) aged 5-10 years, and their age- and sex-matched HIV- controls (n=47). Prevalence of high-density lipoprotein cholesterol (HDL-c) and triglyceride-driven dyslipidemia was higher among treated HIV+ children than in controls (51.6% vs 27.7% respectively, p < 0.019). In a multivariate Poisson regression model adjusted for age, sex and BMI, the association between low HDL-c, hypertriglyceridemia and HIV remained significantly high (for HDL-c: ARR: 0.89, 95% CI: 0.82 – 0.96, p = 0.003; for triglycerides: ARR: 1.54, 95% CI: 1.31 – 1.81, p < 0.001). Among HIV+ children, the use of lopinavir/ritonavir, a protease-based antiretroviral therapy was also associated elevation of triglyceride levels (p = 0.032). Also, HIV+ children had a 2.8-fold reduction of anti-measles IgG titers and 17.1-fold reduction of anti-pertussis toxin IgG levels when compared to HIV- children. Our findings suggest that dyslipidemia and inadequate vaccine-induced antibody responses observed in this population of young African HIV+ children might increase their risk for premature onset of cardiovascular illnesses and acquisition of preventable diseases.
Ultrastructural and Functional Analysis of a Novel Extra-Axonemal Structure in Parasitic Trichomonads
Authors: Coceres Veronica M. , Iriarte Lucrecia S. , Miranda-Magalhães Abigail , Santos de Andrade Thiago André , de Miguel Natalia , Pereira-Neves Antonio
Published: November 2021

Trichomonas vaginalis and Tritrichomonas foetus are extracellular flagellated parasites that inhabit humans and other mammals, respectively. In addition to motility, flagella act in a variety of biological processes in different cell types, and extra-axonemal structures (EASs) have been described as fibrillar structures that provide mechanical support and act as metabolic, homeostatic, and sensory platforms in many organisms. It has been assumed that T. vaginalis and T. foetus do not have EASs. However, here, we used complementary electron microscopy techniques to reveal the ultrastructure of EASs in both parasites. Such EASs are thin filaments (3–5 nm diameter) running longitudinally along the axonemes and surrounded by the flagellar membrane, forming prominent flagellar swellings. We observed that the formation of EAS increases after parasite adhesion on the host cells, fibronectin, and precationized surfaces. A high number of rosettes, clusters of intramembrane particles that have been proposed as sensorial structures, and microvesicles protruding from the membrane were observed in the EASs. Our observations demonstrate that T. vaginalis and T. foetus can connect to themselves by EASs present in flagella. The protein VPS32, a member of the ESCRT-III complex crucial for diverse membrane remodeling events, the pinching off and release of microvesicles, was found in the surface as well as in microvesicles protruding from EASs. Moreover, we demonstrated that the formation of EAS also increases in parasites overexpressing VPS32 and that T. vaginalis-VPS32 parasites showed greater motility in semisolid agar. These results provide valuable data about the role of the flagellar EASs in the cell-to-cell communication and pathogenesis of these extracellular parasites.
COVID-19 in Adults With Hypertrophic Cardiomyopathy
Authors: Arabadjian Milla E. , Reuter Maria C. , Stepanovic Alexandra , Sherrid Mark V. , Massera Daniele
Published: November 2021

Background: Individuals with cardiovascular disease are considered high risk for severe COVID-19. However, the clinical impact of COVID-19 in patients with hypertrophic cardiomyopathy (HCM) is unknown. The purpose of this study was to describe the clinical course and outcomes of COVID-19 in patients with HCM.

Methods: This retrospective observational study included adults with HCM and positive PCR/antibody test for SARS-CoV-2 at a large urban hospital system in the New York from January, 2020 to January, 2021.

Results: Seventy individuals were included, with a mean (SD) age of 60.1 (15.1) years, 39 (55.7%) of whom were male, and 42 (60%) white. Forty-five (65.3%) patients had obstructive HCM. Hypertension and obesity (BMI ≥ 30) were present in 45 (64.3%) and 37 (52.9%) patients, and the prevalence of atrial fibrillation, obstructive sleep apnea and diabetes was high. Common symptoms of COVID-19 were fever, cough, shortness of breath and fatigue, affecting 33 (47.1%), 33 (47.1%), 28 (40.0%), and 28 (40.0%) patients, respectively. Fourteen (20%) patients were hospitalized. The majority (45 [64.3%] patients) recovered without intervention. Two patients had non-fatal pulmonary embolisms, 1 had atrial fibrillation requiring electrical cardioversion and 1 had acute decompensated heart failure. Three (4.3%) patients required mechanical ventilation, two of whom died (case fatality rate 2.9%). A total of 15 (21.4%) patients were asymptomatic.

Conclusions: Our data suggest that in this diverse and high-risk group of patients with HCM, established risk factors for severe COVID-19, such as obesity, may be more important drivers of morbidity and mortality than the presence of HCM alone.
A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells
Authors: Song Xing-Hui , He Ning , Xing Yue-Ting , Jin Xiao-Qin , Li Yan-Wei , Liu Shuang-Shuang , Gao Zi-Ying , Guo Chun , Wang Jia-Jia , Huang Ying-Ying , Hu Hu , Wang Lin-Lin
Published: November 2021

Adipose tissue-derived stromal cells are promising candidates investigating the stem cell-related treatment. However, their proportion and utility in the human body decline with time, rendering stem cells incompetent to complete repair processes in vivo. The involvement of circRNAs in the aging process is poorly understood. Rat subcutaneous adipose tissue from 10-week-old and 27-month-old rats were used for hematoxylin and eosin (H and E) staining, TUNEL staining, and circRNA sequencing. Rat adipose tissue-derived stromal cells were cultured and overexpressed with circ-ATXN2. Proliferation was examined using xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Apoptosis was induced by CoCl2 and examined using flow cytometry. RT-PCR assay and Oil Red O staining were used to measure adipogenesis at 48 h and 14 days, respectively. H and E staining showed that the diameter of adipocytes increased; however, the number of cells decreased in old rats. TUNEL staining showed that the proportion of apoptotic cells was increased in old rats. A total of 4,860 and 4,952 circRNAs was detected in young and old rats, respectively. Among them, 67 circRNAs exhibited divergent expression between the two groups (fold change ≥2, p ≤ 0.05), of which 33 were upregulated (49.3%) and 34 were downregulated (50.7%). The proliferation of circ-ATXN2-overexpressing cells decreased significantly in vitro, which was further validated by xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Overexpression of circ-ATXN2 significantly increased the total apoptotic rate from 5.78 ± 0.46% to 11.97 ± 1.61%, early apoptotic rate from 1.76 ± 0.22% to 5.50 ± 0.66%, and late apoptosis rate from 4.02 ± 0.25% to 6.47 ± 1.06% in adipose tissue-derived stromal cells. Furthermore, in circ-ATXN2-overexpressing cells, RT-PCR assay revealed that the expression levels of adipose differentiation-related genes PPARγ and CEBP/α were increased and the Oil Red O staining assay showed more lipid droplets. Our study revealed the expression profile of circRNAs in the adipose tissue of old rats. We found a novel age-related circular RNA—circ-ATXN2—that inhibits proliferation and promotes cell death and adipogenesis in rat adipose tissue-derived stromal cells.
Citrullinated Epitopes Identified on Tumour MHC Class II by Peptide Elution Stimulate Both Regulatory and Th1 Responses and Require Careful Selection for Optimal Anti-Tumour Responses
Authors: Symonds Peter , Marcu Ana , Cook Katherine W. , Metheringham Rachael L. , Durrant Lindy G. , Brentville Victoria A.
Published: November 2021

Background

Somatic mutations or post-translational modifications of proteins result in changes that enable immune recognition. One such post-translational modification is citrullination, the conversion of arginine residues to citrulline. Citrullinated peptides are presented on MHC class II (MHCII)viaautophagy which is upregulated by cellular stresses such as tumourigenesis.

Methods

Peptides were eluted from B16 melanoma expressing HLA-DP4 and analysed by mass spectrometry to profile the presented citrullinated repertoire. Initially, seven of the identified citrullinated peptides were used in combination to vaccinate HLA-DP4 transgenic mice. Immune responses were characterised from the combination and individual vaccines byex vivocytokine ELISpot assay and assessed for tumour therapy.

Results

The combination vaccine induced only weak anti-tumour therapy in the B16cDP4 melanoma model. Immune phenotyping revealed a dominant IFNγ response to citrullinated matrix metalloproteinase-21 peptide (citMMP21) and an IL-10 response to cytochrome p450 peptide (citCp450). Exclusion of the IL-10 inducing citCp450 peptide from the combined vaccine failed to recover a strong anti-tumour response. Single peptide immunisation confirmed the IFNγ response from citMMP21 and the IL-10 response from citCp450 but also showed that citrullinated Glutamate receptor ionotropic (citGRI) peptide stimulated a low avidity IFNγ response. Interestingly, both citMMP21 and citGRI peptides individually, stimulated strong anti-tumour responses that were significantly better than the combined vaccine. In line with the citGRI T cell avidity, it required high dose immunisation to induce an anti-tumour response. This suggests that as the peptides within the combined vaccine had similar binding affinities to MHC-II the combination vaccine may have resulted in lower presentation of each epitope and weak anti-tumour immunity.

Conclusion

We demonstrate that tumours present citrullinated peptides that can stimulate Th1 and regulatory responses and that competition likely exists between similar affinity peptides. Characterisation of responses from epitopes identified by peptide elution are necessary to optimise selection for tumour therapy.
The Protective Effects of Lactobacillus plantarum KLDS 1.0344 on LPS-Induced Mastitis In Vitro and In Vivo
Authors: Chen Qingxue , Wang Song , Guo Jiayao , Xie Qinggang , Evivie Smith Etareri , Song Yue , Li Bailiang , Huo Guicheng
Published: November 2021

Cow mastitis, which significantly lowers milk quality, is mainly caused by pathogenic bacteria such as E. coli. Previous studies have suggested that lactic acid bacteria can have antagonistic effects on pathogenic bacteria that cause mastitis. In the current study, we evaluated the in vitro and in vivo alleviative effects of L. plantarum KLDS 1.0344 in mastitis treatment. In vitro antibacterial experiments were performed using bovine mammary epithelial cell (bMEC), followed by in vivo studies involving mastitis mouse models. In vitro results indicate that lactic acid was the primary substance inhibiting the E. coli pathogen. Meanwhile, treatment with L. plantarum KLDS 1.0344 can reduce cytokines’ mRNA expression levels in the inflammatory response of bMEC induced by LPS. In vivo, the use of this strain reduced the secretion of inflammatory factors IL-6, IL-1β, and TNF-α, and decreased the activity of myeloperoxidase (MPO), and inhibited the secretion of p-p65 and p-IκBα. These results indicate that L. plantarum KLDS 1.0344 pretreatment can reduce the expression of inflammatory factors by inhibiting the activation of NF-κB signaling pathway, thus exerting prevent the occurrence of inflammation in vivo. Our findings show that L. plantarum KLDS 1.0344 has excellent properties as an alternative to antibiotics and can be developed into lactic acid bacteria preparation to prevent mastitis disease.
Severe Congenital Thrombocytopenia Characterized by Decreased Platelet Sialylation and Moderate Complement Activation Caused by Novel Compound Heterozygous Variants in GNE
Authors: Smolag Karolina I. , Fager Ferrari Marcus , Zetterberg Eva , Leinoe Eva , Ek Torben , Blom Anna M. , Rossing Maria , Martin Myriam
Published: November 2021

Background

Hereditary thrombocytopenias constitute a genetically heterogeneous cause of increased bleeding. We report a case of a 17-year-old boy suffering from severe macrothrombocytopenia throughout his life. Whole genome sequencing revealed the presence of two compound heterozygous variants in GNE encoding the enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, crucial for sialic acid biosynthesis. Sialic acid is required for normal platelet life span, and biallelic variants in GNE have previously been associated with isolated macrothrombocytopenia. Furthermore, sialic acid constitutes a key ligand for complement factor H (FH), an important inhibitor of the complement system, protecting host cells from indiscriminate attack.

Methods

Sialic acid expression and FH binding to platelets and leukocytes was evaluated by flow cytometry. The binding of FH to erythrocytes was assessed indirectly by measuring the rate of complement mediated hemolysis. Complement activation was determined by measuring levels of C3bBbP (alternative pathway), C4d (classical/lectin pathway) and soluble terminal complement complex assays.

Results

The proband exhibited markedly decreased expression of sialic acid on platelets and leukocytes. Consequently, the binding of FH was strongly reduced and moderate activation of the alternative and classical/lectin complement pathways was observed, together with an increased rate of erythrocyte lysis.

Conclusion

We report two previously undescribed variants in GNE causing severe congenital macrothrombocytopenia in a compound heterozygous state, as a consequence of decreased platelet sialylation. The decreased sialylation of platelets, leukocytes and erythrocytes affects the binding of FH, leading to moderate complement activation and increased hemolysis.
Polymers Blending as Release Modulating Tool in Drug Delivery
Authors: Ghasemiyeh Parisa , Mohammadi-Samani Soliman
Published: November 2021

Different polymeric materials have been used as drug delivery vehicles for decades. Natural, semisynthetic, and synthetic polymers each have their own specific characteristics and, due to the physicochemical limitations of each polymer, tuning the release rate and targeting the active ingredient to a specific organ or site of action is a complicated task for pharmaceutical scientists. In this regard, polymer blending has been considered as an attractive approach to fabricate novel and unique drug delivery systems with modified physical and/or chemical characteristics. There are three major polymer blending approaches that are used for drug delivery purposes: physical mixtures, core-shell model, and block copolymer model. Each of these types of polymer blends could significantly affect the loading capacities and the kinetics of drug release from the relevant formulations. Drug release from these blended polymers can be tuned through the changes in temperature and pH of the environment, and physiochemical properties of the target organs. Furthermore, the possible molecular interactions among polymers and drug molecules can significantly affect the drug release profile from these blended polymeric micro- and nanocarriers. In this review, first of all, different types of polymers and their various applications in biomedical sciences have been discussed and smart or stimuli responsive polymers are introduced and categorized based on their nature. Then, the purpose of polymer blending in drug delivery systems has been discussed. Different types of polymer blends including physical mixtures, core-shell polymeric carriers, and block copolymers have been summarized with focus on the effect of polymer blending on encapsulated drug release profiles. Finally, the consequence of each blending approach on drug release profile and kinetics of drug release have been mentioned in tabular format.
Introducing a Novel, Broad Host Range Temperate Phage Family Infecting Rhizobium leguminosarum and Beyond
Authors: Ford Sam , Moeskjær Sara , Young Peter , Santamaría Rosa I. , Harrison Ellie
Published: November 2021

Temperate phages play important roles in bacterial communities but have been largely overlooked, particularly in non-pathogenic bacteria. In rhizobia the presence of temperate phages has the potential to have significant ecological impacts but few examples have been described. Here we characterize a novel group of 5 Rhizobium leguminosarum prophages, capable of sustaining infections across a broad host range within their host genus. Genome comparisons identified further putative prophages infecting multiple Rhizobium species isolated globally, revealing a wider family of 10 temperate phages including one previously described lytic phage, RHEph01, which appears to have lost the ability to form lysogens. Phylogenetic discordance between prophage and host phylogenies suggests a history of active mobilization between Rhizobium lineages. Genome comparisons revealed conservation of gene content and order, with the notable exception of an approximately 5 kb region of hypervariability, containing almost exclusively hypothetical genes. Additionally, several horizontally acquired genes are present across the group, including a putative antirepressor present only in the RHEph01 genome, which may explain its apparent inability to form lysogens. In summary, both phenotypic and genomic comparisons between members of this group of phages reveals a clade of viruses with a long history of mobilization within and between Rhizobium species.
In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study
Authors: Bernabò Nicola , Di Berardino Chiara , Capacchietti Giulia , Peserico Alessia , Buoncuore Giorgia , Tosi Umberto , Crociati Martina , Monaci Maurizio , Barboni Barbara
Published: November 2021

In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic-oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility.