bluuebunny/crossref_metadata_2025 huggingface dataset:
РОЗРОБКА ТА ВИКОРИСТАННЯ ЕЛЕКТРОННОГО ЛАБОРАТОРНОГО ПРАКТИКУМУ «ПЛАН ПОЛЬОТУ» ДЛЯ ПІДГОТОВКИ ДИСПЕТЧЕРІВ ІЗ ЗАБЕЗПЕЧЕННЯ ПОЛЬОТІВ
Authors: Тимошенко Ганна Сергіївна , Данилко Оксана Григорівна , Сагановська Лариса Анатоліївна
Published: February 2021

Стаття присвячена розробці електронного лабораторного практикуму «План польоту». Авторами розглянуто питання щодо доцільності та ефективності введення електронних засобів навчання в освітній процес, оскільки в авіаційному середовищі існує потреба в удосконаленні існуючих та створенні нових електронних засобів навчання у сфері планування польотів і забезпечення екіпажів повітряних суден необхідною інформацією. У процесі дослідження встановлено, що не існує електронних лабораторних практикумів з планування польотів для підготовки майбутніх диспетчерів із забезпечення польотів. Виділено етапи створення та застосування електронних засобів навчання. На етапі проєктування та розробки практикуму створено алгоритм імітації професійної діяльності диспетчера із забезпечення польотів, побудовано структурну схему процесу навчання майбутніх фахівців, що має бути реалізована в лабораторному практикумі. У результаті системного аналізу сформульовано вимоги до електронного лабораторного практикуму «План польоту», представлено схему реалізації компонентів практикуму, а також безпосередньо розроблено інтерфейс електронного засобу навчання «План польоту» з описом усіх його функцій та можливостей. У ході експериментального дослідження, що проводилось на базі Льотної академії Національного авіаційного університету виконано оцінку реалізованих функцій практикуму за техніко-технологічним, психолого-педагогічним та дизайн-критерієм. Зроблено висновок щодо доцільності використання електронного лабораторного практикуму з планування польотів у навчальному процесі, оскільки розроблений електронний засіб навчання дозволяє імітувати професійну діяльність диспетчерів із забезпечення польотів у різних умовах, дає змогу отримати теоретичні знання та набути практичного досвіду з обраної теми, а отже, підвищити якість професійної підготовки авіаційних фахівців.
ТИПОЛОГІЯ ЕЛЕКТРОННИХ РЕСУРСІВ У ФОРМУВАННІ РИТОРИЧНОЇ КУЛЬТУРИ ФАХІВЦЯ
Authors: Будянський Дмитро Васильович , Друшляк Марина Григорівна , Семеніхіна Олена Володимирівна , Харченко Інна Іванівна , Горбачук Василь Олександрович , Чашечникова Ольга Серафимівна
Published: February 2021

У статті на основі тлумачення категорії «риторична культура» як інтегративної особистісної характеристики, що передбачає ґрунтовні знання історії, теорії і методики ораторського мистецтва (етапи підготовки промови, риторичні тропи та фігури, прийоми активізації уваги аудиторії тощо), інтелектуальні, мовленнєві, етичні, естетичні та артистично-виконавські якості, які виражаються у формі оригінального продукту мисленнєво-мовленнєвої діяльності схарактеризовано типологію електронних ресурсів у формуванні риторичної культури вчителя: відеоконтент (промови видатних ораторів минулого і сучасності, фрагменти кінофільмів, театральних вистав, телевізійних програм, виступи майстрів художнього слова, лекції вітчизняних і зарубіжних викладачів, доповіді відомих учених, фрагменти уроків та виховних заходів), аудіоконтент (подкасти, аудіокниги), курси з риторики на освітніх платформах (UDEMY, EDUGET, TED), спеціалізовані ресурси з риторики, спеціалізоване програмне забезпечення в галузі риторики (Тренер Оратора, Ummo, Public Speaking, Черная риторика, Говорилло), соціальні спільноти для онлайн комунікації (Facebook, Instagram, Telegram). Коротко надано описові характеристики кожного типу та наведено відповідні приклади з Інтернет-посиланнями на типовий Інтернет-контент. За проведеним аналізом електронних ресурсів у галузі риторики для формування риторичної культури фахівця найбільш ефективними, на думку експертів (фахівців у галузі ораторського мистецтва), є використання відеоконтенту, а саме: промови видатних ораторів минулого і сучасності, використання аудіоконтенту та використання спеціалізованого програмного забезпечення, що підтверджено коефіцієнтом конкордації Кендала (0,87) та χ^2-критерієм оцінки вірогідності результату χ=26,85, що для рівня значущості 0,05 підтверджує вірогідність висновків експертної групи.
Estratégias do enfermeiro obstetra para diminuição dos métodos intervencionistas durante o parto normal
Authors: Cavalcante Larissa Gonçalves , Barbosa Diogo Amaral , Carvalho Bruno Brandão de , Souza Joice Taiane Anselmo Harter de , Oliveira Rhavenna Thais Silva , Costa Giovanna Felipe Cavalcante , Lima Thiago Oliveira Sabino , Silva Raylton Aparecido Nascimento , Santana Martin Dharlle Oliveira , Abrão Ruhena Kelber
Published: February 2021

Introdução: A atuação do enfermeiro obstetra no cenário da assistência ao parto mostra inúmeras vantagens, no qual o cuidado menos intervencionista acarreta menores riscos para a saúde materna. Objetivo: Identificar as principais estratégias do enfermeiro obstetra para a diminuição dos métodos intervencionistas durante o parto normal. Método: Estudo bibliográfico, descritivo do tipo revisão integrativa da literatura. As bases utilizadas para a coleta de dados foram: BVSalud, SciELO, BDENF, MEDLINE/PubMed e Documentos do Ministério da Saúde (MS), com artigos publicados de 2015 a 2020. Não houve necessidade aprovação pelo Comitê de Ética em Pesquisa. Resultados e Discussão: Os artigos foram selecionados referentes a três categorias: (A) Banho de aspersão; (B) Exercícios facilitadores; e (C) Posição confortável para o parto. Comprovou-se que o banho quente é a estratégia mais utilizada pelo enfermeiro; os principais exercícios facilitadores foram os de respiração, o uso da bola suíça e a deambulação; o incentivo à adoção de posições variadas durante o parto contribui para a melhor evolução do processo de partejar. Conclusão: Existe um leque de possibilidades que o enfermeiro obstetra pode utilizar na assistência ao parto normal, todavia precisam ser implementadas no cotidiano, visto que ainda há grande apego aos métodos tradicionais de parto.
Atualizações científicas sobre a deficiência de vitamina D, de ácido fólico e magnésio na depressão
Authors: Baldoino Fabbio Ronnyel Rodrigues , Mota Giovanna de Aguiar , Cunha Myrella , Melo Hellen Pereira , Garcês Tereza Cristina de Carvalho Souza , Andrade Ana Rachel Oliveira de
Published: February 2021

Objetivo: realizar uma revisão de literatura acerca da influência da deficiência de vitamina D, de metilfolato e de magnésio no desenvolvimento da depressão. Metodologia: Desenvolveu-se uma revisão do tipo integrativa, com estudos publicados entre 2016 e 2020. Inicialmente, estabeleceu-se a questão norteadora, seguida da seleção dos descritores “Deficiência de Vitamina D”; “ácido fólico”, “deficiência de magnésio” e “depressão”, conforme a plataforma dos Descritores em Ciências da Saúde. As bases de dados destinadas para a busca das publicações, foram: Scielo, Medline, Lilacs e Pubmed. Em seguida definiu-se os critérios exclusão e inclusão das publicações. Resultados e Discussão: Assim, a partir do protocolo metodológico empregado, 24 artigos foram selecionados para compor o estudo. A maior parte (n=19, 79,17%) correspondem a publicações que avaliaram de alguma forma a relação da vitamina D com a depressão. Quatro (16,66%) estudos correspondem à relação do ácido fólico, e um (4,17%) ao papel do magnésio nos distúrbios depressivos. Muitos autores observaram que a deficiência de vitamina D encontra-se associada à presença de sintomas depressivos. Contudo, verificou-se uma escassez de estudos científicos que visem avaliar a influência da deficiência o ácido fólico e magnésio no desenvolvimento da depressão. Conclusão: constatou-se que a maior parte estudos concentra-se na associação entre a ausência da vitamina D e depressão, demonstrando que muitos pesquisadores encaram esse micronutriente como um elemento envolvido em tal distúrbio. Entretanto, ressalta-se a necessidade de mais investigações que visem colaborar com o entendimento do papel do folato e do magnésio nas alterações de humor.
Qualidade de luz na multiplicação e enraizamento in vitro de mirtileiro ‘Woodard’
Authors: Cruz Jéssica Gonsalez , Pasa Mateus da Silveira , Dias Camila Schwartz , Loy Flávia , Copatti Andrio Spiller , Sommer Laura Reisdörfer , Deuner Sidnei , Mello-Farias Paulo Celso de
Published: February 2021

O objetivo deste estudo foi avaliar o efeito da qualidade da luz e dos reguladores de crescimento 2-isopentenil adenina (2-ip) e ácido indol 3-butírico (AIB) na multiplicação in vitro e enraizamento do mirtilo ‘Woodard’. Os experimentos foram organizados em um delineamento inteiramente casualizado, com três níveis de qualidade de luz (vermelho, azul e branco) e dois níveis de regulador de crescimento vegetal (presença ou ausência de 100 mg L-1 2-ip ou 0,5 mg L-1 AIB, nos experimentos de multiplicação e enraizamento, respectivamente). Os parâmetros avaliados em ambos os experimentos foram taxa de sobrevivência (%), número de brotos por explante, comprimento dos brotos (cm); número de folhas por explante e área foliar (cm2). No experimento de multiplicação também foi quantificado o conteúdo de pigmentos fotossintéticos [clorofila (chl) a e chl b, chl a + b, e carotenóides] e no ensaio de enraizamento o número e comprimento da raiz. Os resultados mostram que a presença de 2-ip em associação com a luz branca resulta em brotações mais longas, bem como em maior número de brotos e folhas. A maior área foliar foi observada com luz branca. O número e o comprimento da raiz foram maiores na presença de AIB no meio. A associação de luz fluorescente branca e a presença de 2-isopentenil adenina (2-ip) ou ácido indol 3-butírico (AIB) no meio fornece os melhores resultados para multiplicação in vitro e enraizamento, respectivamente, de 'Woodard' mirtilo.
Didactic materials: Mannequin for canine abdominal and vaginal palpation
Authors: Anciuti Andreia Nobre , Varela Junior Antonio Sergio , Ochôa Talita Lobo , Keidann Betina , Corrêa Luisa Grecco , Andrades Josiane de Lima , Corcini Carine Dahl
Published: February 2021

Compared to the veterinary education system decades ago, ethical and welfare questions are of major relevance in the current scenario. Therefore, certain learning practices involving in vivo animal studies are no longer performed. To overcome this limitation, the use of mannequins has emerged as an interactive and immersive method of learning that simulates a real situation. The aim of this work is development mannequins for improve physiology of the reproductive apparatus of a bitch. Here, we used a plastic canine prototype to simulate the abdominal and vaginal palpation technique. An abdominal incision was made, filled with synthetic fiber, and a fictional uterus was placed. In the same mannequin, an orifice was created that correspond to the vagina. This model greatly helped in training students in performing palpation techniques, conducting the static evaluation, and assessing maternal-fetal ratio. Moreover, the physiology of the reproductive canine prototype made possible the demonstration of abdominal and vaginal palpation. This practice of vaginal palpation was found to be of great value since several students could easily take the examination and identify different stages of canine gestation, which could hardly be achieved using animals. Mannequins have received good student acceptance owing to their safety and ease to use, and resulted in a better understanding of the procedure to perform future in vivo animal studies.
Investigation of the Ferredoxin’s Influence on the Anaerobic and Aerobic, Enzymatic H2 Production
Authors: Koo Jamin , Cha Yeeun
Published: February 2021

Ferredoxins are metalloproteins that deliver electrons to several redox partners, including [FeFe] hydrogenases that are potentially a component of biological H2 production technologies. Reduced ferredoxins can also lose electrons to molecular oxygen, which may lower the availability of electrons for cellular or synthetic reactions. Ferredoxins thus play a key role in diverse kinds of redox biochemistry, especially the enzymatic H2 production catalyzed by [FeFe] hydrogenases. We investigated how the yield of anaerobic and aerobic H2 production vary among the four different types of ferredoxins that are used to deliver electrons extracted from NADPH within the synthetic, fermentative pathway. We also assessed the electron loss due to O2 reduction by reduced ferredoxins within the pathway, for which the difference was as high as five-fold. Our findings provide valuable insights for further improving biological H2 production technologies and can also facilitate elucidation of mechanisms governing interactions between Fe–S cluster(s) and molecular oxygen.
Gain-of-Function STIM1 L96V Mutation Causes Myogenesis Alteration in Muscle Cells From a Patient Affected by Tubular Aggregate Myopathy
Authors: Conte Elena , Pannunzio Alessandra , Imbrici Paola , Camerino Giulia Maria , Maggi Lorenzo , Mora Marina , Gibertini Sara , Cappellari Ornella , De Luca Annamaria , Coluccia Mauro , Liantonio Antonella
Published: February 2021

Tubular Aggregate Myopathy (TAM) is a hereditary ultra-rare muscle disorder characterized by muscle weakness and cramps or myasthenic features. Biopsies from TAM patients show the presence of tubular aggregates originated from sarcoplasmic reticulum due to altered Ca2+ homeostasis. TAM is caused by gain-of-function mutations in STIM1 or ORAI1, proteins responsible for Store-Operated-Calcium-Entry (SOCE), a pivotal mechanism in Ca2+ signaling. So far there is no cure for TAM and the mechanisms through which STIM1 or ORAI1 gene mutation lead to muscle dysfunction remain to be clarified. It has been established that post-natal myogenesis critically relies on Ca2+ influx through SOCE. To explore how Ca2+ homeostasis dysregulation associated with TAM impacts on muscle differentiation cascade, we here performed a functional characterization of myoblasts and myotubes deriving from patients carrying STIM1 L96V mutation by using fura-2 cytofluorimetry, high content imaging and real-time PCR. We demonstrated a higher resting Ca2+ concentration and an increased SOCE in STIM1 mutant compared with control, together with a compensatory down-regulation of genes involved in Ca2+ handling (RyR1, Atp2a1, Trpc1). Differentiating STIM1 L96V myoblasts persisted in a mononuclear state and the fewer multinucleated myotubes had distinct morphology and geometry of mitochondrial network compared to controls, indicating a defect in the late differentiation phase. The alteration in myogenic pathway was confirmed by gene expression analysis regarding early (Myf5, Mef2D) and late (DMD, Tnnt3) differentiation markers together with mitochondrial markers (IDH3A, OGDH). We provided evidences of mechanisms responsible for a defective myogenesis associated to TAM mutant and validated a reliable cellular model usefull for TAM preclinical studies.
Tissue Regeneration Capacity of Extracellular Vesicles Isolated From Bone Marrow-Derived and Adipose-Derived Mesenchymal Stromal/Stem Cells
Authors: Liu Yuan , Holmes Christina
Published: February 2021

Mesenchymal stem cell (MSC)-based therapies have demonstrated tissue repair and regeneration capacity in various preclinical models. These therapeutic effects have recently been largely attributed to the paracrine effects of the MSC secretome, including proteins and extracellular vesicles (EVs). EVs are cell-secreted nano-sized vesicles with lipid bilayer membranes that facilitate cell–cell signaling. Treatments based on MSC-derived EVs are beginning to be explored as an alternative to MSC transplantation-based therapies. However, it remains to be determined which MSC source produces EVs with the greatest therapeutic potential. This review compares the tissue regeneration capacity of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, with a particular focus on their angiogenic, osteogenic, and immunomodulatory potentials. Other important issues in the development of MSC-derived EV based therapies are also discussed.
A Rapid NGS-Based Preimplantation Genetic Testing for Chromosomal Abnormalities in Day-3 Blastomere Biopsy Allows Embryo Transfer Within the Same Treatment Cycle
Authors: Ye Yinghui , Ma Jieliang , Cui Long , Lu Sijia , Jin Fan
Published: February 2021

Nowadays, most of the preimplantation genetic testing (PGT) is performed with a strategy of comprehensive chromosome screening and trophectoderm biopsy. Nevertheless, patients with ovarian insufficiency may not have competent blastocysts. In the present study, we aimed to establish the value of multiple annealing and looping-based amplification cycle (MALBAC)-based next-generation sequencing (NGS) for PGT in day-3 embryos. A total of 94.3% (1168/1239) of embryos yielded informative results, and the overall embryo euploid rate was 21.9% (256/1168). Overall, 225 embryos were transferred in 169 cycles with a clinical pregnancy rate of 49.1% (83/169). The live birth and implantation rates were 47.3% (80/169) and 44.4% (100/225), respectively. Double embryos transfer showed higher clinical pregnancy and live birth rates compared with single embryo transfer, but the implantation rates were similar (44.2% vs. 44.6%,P> 0.05). The euploid rate for reciprocal translocations (16.1%) was significantly lower than that for Robertsonian translocations (28.0%,P< 0.01) and inversions (28.0%,P< 0.01). However, higher percentages of embryos withde novoabnormalities were observed with Robertsonian translocations (23.3%,P< 0.01) and inversions (30.5%,P< 0.01) than with reciprocal translocations (11.6%). We demonstrated that NGS for PGT on day-3 embryos is an effective clinical application, particularly for patients with a diminished ovarian reserve and limited embryos.
Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease
Authors: Maghrebi Olfa , Hanachi Mariem , Bahrini Khadija , Kchaou Mariem , Jeridi Cyrine , Belal Samir , Ben Sassi Samia , Barbouche Mohamed-Ridha , Souiai Oussama , Belghith Meriam
Published: February 2021

Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.
Submission for Special Issue: The Role of Platelet Activation in the Pathophysiology of HIV, Tuberculosis, and Pneumococcal Disease. Bedaquiline Suppresses ADP-Mediated Activation of Human Platelets In Vitro via Interference With Phosphatidylinositol 3-Kinase
Authors: Tintinger Gregory R. , Theron Annette J. , Steel Helen C. , Cholo Moloko C. , Nel Jan G. , Feldman Charles , Anderson Ronald
Published: February 2021

Although bedaquiline has advanced the treatment of multidrug-resistant tuberculosis (TB), concerns remain about the cardiotoxic potential of this agent, albeit by unexplored mechanisms. Accordingly, we have investigated augmentation of the reactivity of human platelets in vitro as a potential mechanism of bedaquiline-mediated cardiotoxicity. Platelet-rich plasma (PRP) or isolated cells prepared from the blood of healthy, adult humans were treated with bedaquiline (0.625–10 µg/ml), followed by activation with adenosine 5’-diphosphate (ADP), thrombin or the thromboxane A2 receptor agonist (U46619). Expression of platelet CD62P (P-selectin), platelet aggregation, Ca2+ fluxes and phosphorylation of Akt1 were measured using flow cytometry, spectrophotometry, fluorescence spectrometry, and by ELISA procedures, respectively. Exposure to bedaquiline caused dose-related inhibition of ADP-activated, but not thrombin- or U46619-activated, expression of CD62P by platelets, achieving statistical significance at a threshold concentration of 5 µg/ml and was paralleled by inhibition of aggregation and Ca2+ mobilization. These ADP-selective inhibitory effects of bedaquiline on platelet activation were mimicked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), implicating PI3-K as being a common target of both agents, a contention that was confirmed by the observed inhibitory effects of bedaquiline on the phosphorylation of Akt1 following activation of platelets with ADP. These apparent inhibitory effects of bedaquiline on the activity of PI3-K may result from the secondary cationic amphiphilic properties of this agent. If operative in vivo, these anti-platelet effects of bedaquiline may contribute to ameliorating the risk of TB-associated cardiovascular disease, but this remains to be explored in the clinical setting.
Analysis of the Characteristics of TIGIT-Expressing CD3−CD56+NK Cells in Controlling Different Stages of HIV-1 Infection
Authors: Zhang Xin , Lu Xiaofan , Cheung Allen Ka Loon , Zhang Qiuyue , Liu Zhiying , Li Zhen , Yuan Lin , Wang Rui , Liu Yan , Tang Bin , Xia Huan , Wu Hao , Zhang Tong , Su Bin
Published: February 2021

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96−CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT−NK cells, while CD96+CD226− cells expanded. Reduced CD96−CD226+ cells and elevated CD96+CD226− cells among NK cells especially TIGIT−NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A−NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C−NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A−NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT−NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT−NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT−NK cells, except for TNF-α−CD107a+IFN-γ−NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.
Increased sCD163 and sCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients With Severe COVID-19 Pneumonia
Authors: Zingaropoli Maria Antonella , Nijhawan Parni , Carraro Anna , Pasculli Patrizia , Zuccalà Paola , Perri Valentina , Marocco Raffaella , Kertusha Blerta , Siccardi Guido , Del Borgo Cosmo , Curtolo Ambrogio , Ajassa Camilla , Iannetta Marco , Ciardi Maria Rosa , Mastroianni Claudio Maria , Lichtner Miriam
Published: February 2021

Background

Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects).

Methods

On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups.

Results

Compared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1–68.4] specificity 73.8% [CI: 58.9–84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492).

Conclusions

The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.
The Challenges of Managing Depredation and Bycatch of Toothed Whales in Pelagic Longline Fisheries: Two U.S. Case Studies
Authors: Fader Joseph E. , Elliott Brianna W. , Read Andrew J.
Published: February 2021

Direct interactions with fisheries are broadly recognized as the leading conservation threat to small cetaceans. In open-ocean environments, one of the primary gear types implicated in these interactions is the pelagic longline. Unlike accidental entanglement in driftnets or deliberate entrapment by purse-seines, interactions between cetaceans and longlines are often driven by attraction of the animals to feed on bait or fish secured on the gear, a behavior known as depredation. Many small and medium-sized delphinid species have learned to exploit such opportunities, leading to economic costs to fisheries and a risk of mortality to the animals from either retaliation by fishermen or hooking or entanglement in fishing gear. Two pelagic longline fisheries in the United States experience depredation and bycatch by odontocete depredators: the Hawai‘i deep-set longline fishery, which is depredated primarily by false killer whales (Pseudorca crassidens), and the Atlantic pelagic longline fishery depredated primarily by short-finned pilot whales (Globicephala macrorhynchus). These fisheries are among the most intensively documented and managed pelagic longline fisheries in the world, with high levels of observer coverage, and bycatch mitigation measures required to reduce the mortality of seabirds, sea turtles and cetaceans. Both fisheries have active, multi-stakeholder “Take Reduction Teams,” enacted under the U.S. Marine Mammal Protection Act (MMPA), that are tasked to develop measures to reduce the bycatch of cetaceans below statutory reference points. Consequently, these two Teams represent model processes within which to address depredation and bycatch, having access to detailed, high-quality data on the nature and frequency of interactions with cetaceans, meaningful stakeholder involvement, resources to test potential solutions, and the institutional will to improve outcomes. We review how mitigation strategies have been considered, developed, and implemented by both Teams and provide a critical analysis of their effectiveness in addressing these problems. Notably, in the absence of straightforward avoidance or deterrence strategies, both Teams have developed gear and handling strategies that depend critically on comprehensive observer coverage. Lessons offered from these Teams, which have implemented consensus-driven management measures under a statutory framework, provide important insights to managers and scientists addressing other depredation problems.
Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study
Authors: Henry Nicolas , Mellaza Chloé , Fage Nicolas , Beloncle François , Genevieve Franck , Legendre Guillaume , Orvain Corentin , Garnier Anne-Sophie , Cousin Maud , Besson Virginie , Subra Jean-François , Duveau Agnès , Augusto Jean-François , Brilland Benoit
Published: February 2021

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice.

Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes.

Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death.

Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.
Effect of Ocean Acidification on Bacterial Metabolic Activity and Community Composition in Oligotrophic Oceans, Inferred From Short-Term Bioassays
Authors: Hu Caiqin , Li Xiangfu , He Maoqiu , Jiang Peng , Long Aimin , Xu Jie
Published: February 2021

Increasing anthropogenic CO2emissions in recent decades cause ocean acidification (OA), affecting carbon cycling in oceans by regulating eco-physiological processes of plankton. Heterotrophic bacteria play an important role in carbon cycling in oceans. However, the effect of OA on bacteria in oceans, especially in oligotrophic regions, was not well understood. In our study, the response of bacterial metabolic activity and community composition to OA was assessed by determining bacterial production, respiration, and community composition at the low-pCO2(400 ppm) and high-pCO2(800 ppm) treatments over the short term at two oligotrophic stations in the northern South China Sea. Bacterial production decreased significantly by 17.1–37.1 % in response to OA, since bacteria with high nucleic acid content preferentially were repressed by OA, which was less abundant under high-pCO2treatment. Correspondingly, shifts in bacterial community composition occurred in response to OA, with a high fraction of the small-sized bacteria and high bacterial species diversity in a high-pCO2scenario at K11. Bacterial respiration responded to OA differently at both stations, most likely attributed to different physiological responses of the bacterial community to OA. OA mitigated bacterial growth efficiency, and consequently, a larger fraction of DOC entering microbial loops was transferred to CO2.
Case Report: Complete Response of Recurrent and Metastatic Cystadenocarcinoma of the Parotid Gland With a Single Course of Combined Nivolumab and Ipilimumab Therapy
Authors: Nakamura Yoshiyuki , Nakayama Masahiro , Nishimura Bungo , Okiyama Naoko , Tanaka Ryota , Ishitsuka Yosuke , Matsumoto Shin , Fujisawa Yasuhiro
Published: February 2021

Although cystadenocarcinoma is classified as a low-grade histological subtype of salivary gland carcinoma (SGC), recurrence and metastases sometimes develop. However, standard treatments for advanced cases have not yet been established. Here, we present a case of unresectable local recurrence and cervical lymph node metastases of cystadenocarcinoma of the parotid gland with multiple lung nodules, all of which showed complete response with only a single course of combined nivolumab and ipilimumab therapy. The patient's medical history of metastatic melanoma roused our suspicions that the multiple lung nodules were cystadenocarcinoma metastases or malignant melanoma. Combination therapy was used based on our suspected diagnosis of lung metastases of melanoma although histological examination of the lung nodules could not be performed. While various chemotherapies are used for advanced SGCs including cystadenocarcinoma, overall, the results are unsatisfactory. In contrast, there have not yet been any reports of advanced cystadenocarcinoma of the salivary gland treated with immune checkpoint inhibitors (ICIs). Given that, in our case, a single course of combined ICI therapy induced a complete response in the unresectable and lymph node metastases from the cystadenocarcinoma and the multiple lung nodules, ICIs, including combined therapy, could be a promising treatment for advanced cystadenocarcinoma.
Optimizing Adjuvant Stereotactic Radiotherapy of Motor-Eloquent Brain Metastases: Sparing the nTMS-Defined Motor Cortex and the Hippocampus
Authors: Dzierma Yvonne , Schuermann Michaela , Melchior Patrick , Nuesken Frank , Oertel Joachim , Rübe Christian , Hendrix Philipp
Published: February 2021

Brain metastases can effectively be treated with surgical resection and adjuvant stereotactic radiotherapy (SRT). Navigated transcranial magnetic stimulation (nTMS) has been used to non-invasively map the motor cortex prior to surgery of motor eloquent brain lesions. To date, few studies have reported the integration of such motor maps into radiotherapy planning. The hippocampus has been identified as an additional critical structure of radiation-induced deficits. The aim of this study is to assess the feasibility of selective dose reduction to both the nTMS-based motor cortex and the hippocampi in SRT of motor-eloquent brain metastases. Patients with motor-eloquent brain metastases undergoing surgical resection and adjuvant SRT between 07/2014 and 12/2018 were retrospectively analyzed. The radiotherapy treatment plans were retrieved from the treatment planning system (“original” plan). For each case, two intensity-modulated treatment plans were created: the “motor” plan aimed to reduce the dose to the motor cortex, the “motor & hipp” plan additionally reduce the dose to the hippocampus. The optimized plans were compared with the “original” plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR). 69 plans were analyzed, all of which were clinically acceptable with no significant differences for PTV coverage. All OAR were protected according to standard protocols. Sparing of the nTMS motor map was feasible: mean dose 9.66 ± 5.97 Gy (original) to 6.32 ± 3.60 Gy (motor) and 6.49 ± 3.78 Gy (motor & hipp), p<0.001. In the “motor & hipp” plan, dose to the ipsilateral hippocampi could be significantly reduced (max 1.78 ± 1.44 Gy vs 2.49 ± 1.87 Gy in “original”, p = 0.003; mean 1.01 ± 0.92 Gy vs. 1.32 ± 1.07 Gy in “original”, p = 0.007). The study confirms the results from previous studies that inclusion of nTMS motor information into radiotherapy treatment planning is possible with a relatively straightforward workflow and can achieve reduced doses to the nTMS-defined motor area without compromising PTV coverage. Furthermore, we demonstrate the feasibility of selective dose reduction to the hippocampus at the same time. The clinical significance of these optimized plans yet remains to be determined. However, with no apparent disadvantages these optimized plans call for further and broader exploration.
Continuous Renal Replacement Therapy: A Review of Use and Application in Pediatric Hematopoietic Stem Cell Transplant Recipients
Authors: Elbahlawan Lama , Bissler John , Morrison R. Ray
Published: February 2021

Hematopoietic stem cell transplant (HSCT) is a curative therapy for malignant and non-malignant conditions. However, complications post-HSCT contribute to significant morbidity and mortality in this population. Acute kidney injury (AKI) is common in the post-allogeneic transplant phase and contributes to morbidity in this population. Continuous renal replacement therapy (CRRT) is used often in the setting of AKI or multiorgan dysfunction in critically ill children. In addition, CRRT can be useful in many disease processes related to transplant and can potentially improve outcomes in this population. This review will focus on the use of CRRT in critically ill children in the post-HSCT setting outside the realm of acute renal failure and highlight the benefits and applications of this modality in this high-risk population.
Ginsenoside Rb1 Alleviates Alcohol-Induced Liver Injury by Inhibiting Steatosis, Oxidative Stress, and Inflammation
Authors: Lai Yuqi , Tan Qinxiang , Xv Shu , Huang Sha , Wang Yuhua , Li Yunjia , Zeng Ting , Mo Chan , Chen Yuyao , Huang Shaohui , Zhou Chuying , Gao Lei , Lv Zhiping
Published: February 2021

Alcoholic liver disease (ALD) has become a heavy burden on health worldwide. Ginsenoside Rb1 (GRb1), extracted from Panax quinquefolium L., has protective effects on many diseases, but the effect and mechanisms of GRb1 on ALD remain unknown. This study aimed to investigate the protective effects of GRb1 on ALD and to discover the potential mechanisms. Zebrafish larvae were exposed to 350 mM ethanol for 32 h to establish a model of acute alcoholic liver injury, and the larvae were then treated with 6.25, 12.5, or 25 μM GRb1 for 48 h. The human hepatocyte cell line was stimulated by 100 mM ethanol and meanwhile incubated with 6.25, 12.5, and 25 μM GRb1 for 24 h. The lipid changes were detected by Oil Red O staining, Nile Red staining, and triglyceride determination. The antioxidant capacity was assessed by fluorescent probes in vivo, and the expression levels of inflammatory cytokines were detected by immunohistochemistry, immunofluorescence, and quantitative real-time PCR. The results showed that GRb1 alleviated lipid deposition in hepatocytes at an optimal concentration of 12.5 μM in vivo. GRb1 reversed the reactive oxygen species accumulation caused by alcohol consumption and partially restored the level of glutathione. Furthermore, GRb1 ameliorated liver inflammation by inhibiting neutrophil infiltration in the liver parenchyma and downregulating the expression of nuclear factor-kappa B pathway-associated proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1β. This study revealed that GRb1 has a protective effect on alcohol-induced liver injury due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions. These findings suggest that GRb1 may be a promising candidate against ALD.
Tissue-Engineered Skeletal Muscle Models to Study Muscle Function, Plasticity, and Disease
Authors: Khodabukus Alastair
Published: February 2021

Skeletal muscle possesses remarkable plasticity that permits functional adaptations to a wide range of signals such as motor input, exercise, and disease. Small animal models have been pivotal in elucidating the molecular mechanisms regulating skeletal muscle adaptation and plasticity. However, these small animal models fail to accurately model human muscle disease resulting in poor clinical success of therapies. Here, we review the potential ofin vitrothree-dimensional tissue-engineered skeletal muscle models to study muscle function, plasticity, and disease. First, we discuss the generation and function ofin vitroskeletal muscle models. We then discuss the genetic, neural, and hormonal factors regulating skeletal muscle fiber-typein vivoand the ability of currentin vitromodels to study muscle fiber-type regulation. We also evaluate the potential of these systems to be utilized in a patient-specific manner to accurately model and gain novel insights into diseases such as Duchenne muscular dystrophy (DMD) and volumetric muscle loss. We conclude with a discussion on future developments required for tissue-engineered skeletal muscle models to become more mature, biomimetic, and widely utilized for studying muscle physiology, disease, and clinical use.
Efficacy of Whole-Body Electromyostimulation (WB-EMS) on Body Composition and Muscle Strength in Non-athletic Adults. A Systematic Review and Meta-Analysis
Authors: Kemmler Wolfgang , Shojaa Mahdieh , Steele James , Berger Joshua , Fröhlich Michael , Schoene Daniel , von Stengel Simon , Kleinöder Heinz , Kohl Matthias
Published: February 2021

This systematic review and meta-analysis set out to determine the efficacy on whole-body electromyostimulation (WB-EMS) on body composition and strength parameters in non-athletic cohorts. A systematic review of the literature according to the PRISMA statement included (a) controlled trials, (b) WB-EMS trials with at least one exercise and one control group, (c) WB-EMS as primary physical intervention, (d) WB-EMS with at least six electrodes covering most muscle groups, (e) non-athletic cohorts. We searched eight electronic databases up to June 30, 2020, without language restrictions. Standardized mean differences (SMD) for muscle mass parameters, total body fat mass, maximum leg extension, and trunk extension strength were defined as outcome measures. In summary, 16 studies with 19 individual WB-EMS groups representing 897 participants were included. Studies vary considerably with respect to age, BMI, and physical conditions. Impulse protocols of the studies were roughly comparable, but training frequency (1–5 sessions/week) and intervention length (6–54 weeks) differed between the studies. SMD average was 1.23 (95%-CI: 0.71–1.76) for muscle mass, 0.98 (0.74–1.22) for maximum leg, and 1.08 (0.78–1.39) for maximum trunk extension strength changes (all p < 0.001). SMD for body fat changes (−0.40, [−0.98 to 0.17]), however, did not reach significance. I2 and Q-statistics revealed substantial heterogeneity of muscle and fat mass changes between the trials. However, rank and regression tests did not indicate positive evidence for small-study bias and funnel plot asymmetries. This work provided further evidence for significant, large-sized effects of WB-EMS on muscle mass and strength parameters, but not on body fat mass.

Clinical Trial Registration:ClinicalTrials.gov, PROSPERO; ID: CRD42020183059.
Vascular and Macrophage Heme Oxygenase-1 in Hypertension: A Mini-Review
Authors: Martínez-Casales Marta , Hernanz Raquel , Alonso María J.
Published: February 2021

Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory). In hypertension, M1 phenotype predominates, producing inflammatory cytokines and oxidative stress, and mediating many mechanisms involved in the pathogenesis of this disease. The increase in the renin–angiotensin system and sympathetic activity contributes to the macrophage mobilization and to its polarization to the pro-inflammatory phenotype. Heme oxygenase-1 (HO-1), a phase II detoxification enzyme responsible for heme catabolism, is induced by oxidative stress, among others. HO-1 has been shown to protect against oxidative and inflammatory insults in hypertension, reducing end organ damage and blood pressure, not only by its expression at the vascular level, but also by shifting macrophages toward the anti-inflammatory phenotype. The regulatory role of heme availability for the synthesis of enzymes involved in hypertension development, such as cyclooxygenase or nitric oxide synthase, seems to be responsible for many of the beneficial HO-1 effects; additionally, the antioxidant, anti-inflammatory, antiapoptotic, and antiproliferative effects of the end products of its reaction, carbon monoxide, biliverdin/bilirubin, and Fe2+, would also contribute. In this review, we analyze the role of HO-1 in hypertensive pathology, focusing on its expression in macrophages.