bluuebunny/crossref_metadata_2025 huggingface dataset:
Estudo clínico randomizado sobre a influência da motivação e acompanhamento de profissionais de saúde na prática de aleitamento materno
Authors: Rocha Najara Barbosa da , Moimaz Suzely Adas Saliba
Published: May 2021

Este estudo objetivou avaliar o impacto da intervenção: motivação e acompanhamento por profissionais de saúde na duração e exclusividade do aleitamento materno, por meio de um estudo clínico randomizado. As gestantes foram entrevistadas (n=154) e acompanhadas até sexto mês após parto. Todas receberam panfleto e assistiram vídeo sobre promoção do aleitamento materno na primeira entrevista na gestação, sendo divididas aleatoriamente em grupos: intervenção (n=51) e controle (n=103).  O grupo de intervenção recebeu acompanhamento domiciliar aos 5 dias e retorno telefônico em 2 e 14 semanas após o parto. Após 6 meses de acompanhamento, 124 mães (Intervenção=50 e Controle=74) foram entrevistadas. A idade média das mães foi 26,5(±6.1) anos, sendo a maioria: cor de pele não-branca (58,9%), morava com companheiro (79%), até 8 anos de estudo (70,2%); multípara (64,5%); não trabalhava (54,8%) e recebia até 2 Salários Mínimos (81,4%). A maioria dos bebês era do sexo masculino (52,4%) e nascido de parto cesárea (61,3%). A taxa de aleitamento materno exclusivo foi 84%, 82%, 54% e 34% aos 5 dias, 2 semanas, 14 semanas e 6 meses respectivamente no grupo Intervenção e 17,6% aos 6 meses no grupo Controle. O grupo intervenção teve maior taxa de aleitamento exclusivo (p=0,03, RR 1,25) e aleitamento materno (p=0,02, RR 2,03) em relação ao controle. A intervenção estudada promoveu alterações positivas na duração e exclusividade do aleitamento materno aos 6 meses de idade, em comparação a educação em saúde tradicional, e pode ser usada na promoção da prática do aleitamento materno pelos serviços de saúde.
Microbiological evaluation of the meat from young collared peccaries (Pecari tajacu Linnaeus, 1758)
Authors: Souza Joyce Galvão de , Cavalcanti Aline Antas Cordeiro , Falcão Brunna Muniz Rodrigues , Siqueira Iara Nunes de , Carreiro Artur da Nóbrega , Figuerêdo Moana Barbosa dos Santos , Batista Luan Nascimento , Medeiros Filipe Jordão Pereira de , Sales José Emanuel de Souza , Oliveira Moacir Franco de , Medeiros Nara Geanne de Araújo , Menezes Danilo José Ayres de
Published: May 2021

The increased demand for meat from wild animals for human consumption, as an alternative protein source, brings with it the need for research that demonstrates the quality of such product. The technical information about the meat from collared peccaries still needs studies and aiming to collaborate with the already existing knowledge, this research had as its objective to provide subsidies for evaluation of the sanitary quality of the meat from collared peccaries. Twelve animals were used, six males and six females, aged four to five months, from the breeding stock of the Federal Rural University of the Semi-Arid and, after euthanasia by a slaughter technique used in goats, the meat samples were collected through sterile swabs at the locations of the hind leg, loin, belly and axilla of each animal, totaling 48 samples. The maximum mesophilic count found was 1.9 x 103 CFU/ml, the total coliform and thermotolerant coliform counts were below the one determined in the legislation for meat from domestic animals, however, through biochemical tests, the presence of E. coli from the biotype 1 and biotype 2 was found, in seven and six samples, respectively. Search results for Salmonella spp. were negative in all samples and, as for Staphylococcus spp., only one sample had the count above the level allowed by law. The contamination load related to the bacteria E. coli proved to be high, making 13 samples unfit for consumption. Regarding the other data, the meat from young collared peccaries showed a low contamination load.
Estresse ocupacional em docentes de enfermagem: Uma revisão integrativa da literatura
Authors: Lenz Catia Aguiar , Antunes Michele , Santos Raquel de Lima dos , Bez Marta Rosecler
Published: May 2021

A profissão do docente do ensino superior é caracterizada por sobrecargas, intensas mudanças e pressões que conduzem a diversas consequências. Objetivo foi identificar as causas do estresse ocupacional em docentes de enfermagem. Trata-se de uma revisão integrativa da literatura, nas bases de dados Literatura Latino-Americana em Ciências de Saúde (LILACS) e na Base de dados em Enfermagem (BDENF). Artigos publicados pela área da saúde, em Língua Portuguesa, no período de 2009 a maio de 2020, completos de acesso livre e online.  Identificaram-se um total de 06 artigos. As discussões apresentadas pelos autores foram descritas em duas categorias. Este estudo traz como resultados os seguintes fatores e/ou situações geradoras de estresse: condições de trabalho; questões éticas; carga mental intensa; falta de reconhecimento profissional; aulas teórico-práticas; associação dos serviços de ensino e saúde; relação interpessoal; situações familiares/social, financeiras e de saúde e entre as principais complicações: estresse, ansiedade, insônia e dificuldades do sono, cefaleia, insuficiência vascular, dor, cansaço, edemas, entre outros problemas. O estudo evidenciou a diversidade e complexidade de diagnosticar os fatores estressores, assim como as complicações a saúde do docente de nível superior.
Caracterização topográfica e de rugosidade de filme fino semicondutor por microscopia confocal
Authors: Sousa Nathália de Paula , Silva Camila Ferreira da , Medeiros Ronaldo Gomes de Castro , Freitas Patricia Guimarães Monteiro de , Zenóbio Isadora Rapoza
Published: May 2021

A caracterização de filmes finos é uma técnica de alta demanda devido a sua vasta utilização em engenharia e ciências. A Microscopia Confocal de Varredura a Laser (MCVL) é um marco da microscopia moderna, aliando alta sensibilidade e velocidade, possibilitando a detecção de imagens de super resolução e análise de dados quantitativa em termos de mapeamento de irregularidades superficiais. O microscópio confocal permite a captura de uma região de interesse desprezando feixes desnecessários e possibilitando a construção de imagens 3D. Atualmente os materiais semicondutores estão se tornando cada vez mais relevantes na sociedade moderna. Suas aplicações se destacam pela capacidade de obter alto desempenho em dispositivos microeletrônicos. Este estudo tem como objetivo demonstrar o uso do microscópio confocal como uma ferramenta eficaz para o mapeamento topográfico, bem como para a investigação dos parâmetros de rugosidade aplicados a um filme fino de SiNx semicondutor. Através deste equipamento foi possível coletar dados e realizar uma meticulosa análise da superfície do material.
O papel do enfermeiro preceptor na residência de enfermagem em uma instituição militar
Authors: Silva Tuane Carla Moreira da , Andrade Pâmela Oliveira de , Costa Andréia Jorge da , Souza Sônia Regina de , Souza Vinícius Rodrigues de , Valente Geilsa Soraia Cavalcanti , Almeida Inez Silva de
Published: May 2021

Objetivo: Compreender o papel do enfermeiro preceptor no processo de treinamento em serviço dos residentes de enfermagem. Metodologia: Estudo qualitativo, descritivo e exploratório, em que participaram onze enfermeiras de um hospital militar. Utilizou-se para coleta de dados um questionário semiestruturado contendo perguntas relacionadas as atribuições e percepções dos preceptores junto aos residentes de enfermagem.  Os dados foram analisados e agrupados em quatro categorias temáticas, sendo discutidos à luz de estudiosos ligados à temática. Resultados: Compreendeu-se que o preceptor é um mediador do conhecimento e formação profissional de residentes, adota estratégias de ensino-aprendizagem para facilitar a troca de conhecimentos e estabelece relações pautadas no respeito mútuo, na confiança e na autonomia de seus alunos. Conclusão: A instituição de saúde precisa incentivar o aprimoramento de competências e habilidades dos preceptores a fim de alcançar a excelência do processo de ensino, uma vez que o conhecimento não é estático e a educação deve acompanhar as inovações científicas e exigências do mercado de trabalho e sociedade.
A implantação de um protocolo de sepse no atendimento do pronto socorro e o impacto nos custos em um hospital privado na Região Amazônica
Authors: Veríssimo Adriana de Oliveira Lameira , Gomes Galvane Teixeira , Souza Alzira Carvalho Paula de , Pastana Caroline Dias , Madeira Juliana Maroja Serafico , Garcia João Victor Moura , Sobrinho Edgar de Brito
Published: May 2021

Objective: To analyze the economic impact of implementing an early sepsis detection protocol in the emergency department of a private hospital in the city of Belém, Pará, Brazil. Methods: Experimental, cross-sectional, retrospective study, carried out from March 2015 to December 2019 from a highly complex referral Center. The implementation of the protocol took place in March 2015. Results: A total of 257 patients were studied, 128 from the group before the protocol (AP group) and 129 belonging to the group after the protocol (DP group), with similar proportions. in relation to sex. Regarding the mean age and standard deviation, in the AP group it was 73.5 ± 23.3 and in the DP group 76.0 ± 17.0. After the implantation of the protocol, there was a reduction in the time of organ dysfunction, mortality rate, ICU stay and hospital stay, both with statistical difference of p = 0.0015, p = 0.04, p = 0.012 and p = 0.0401, respectively. In the evaluation of hospital costs, a reduction in the average spent with each patient was identified both in the total cost of hospitalization and in the total cost referring only to the length of stay in the ICU. Conclusion: It is noticeable that sepsis costs are a public health problem both nationally and internationally. However, such expenses can be reduced with the implementation of protocols that aim to standardize the care provided to patients and thereby positively influence the reduction of hospital stay, hospitalization costs and mortality.
Cisto da bifurcação vestibular: Relato de caso clínico
Authors: Custódio Gustavo Paiva , Calderoni Ana Maria de Paula , Melo Alice Rodrigues Feres de , Caetano Roberta Mansur , Vilela Danúsia da Silva
Published: May 2021

O cisto da bifurcação vestibular é um cisto odontogênico inflamatório incomum que se desenvolve na face vestibular do primeiro molar inferior permanente, em crianças de 5 a 13 anos. Clinicamente apresenta sensibilidade, edema, bolsa periodontal e secreção com gosto desagradável. Radiograficamente, se mostra como uma lesão radiolúcida unilocular e bem delimitada envolvendo a bifurcação vestibular e a região da raiz do dente em questão. Os ápices radiculares dos molares estão, caracteristicamente, voltados para a cortical lingual mandibular. Este estudo teve como objetivo relatar um caso clínico de uma criança com cisto da bifurcação vestibular. Trata-se de um paciente do gênero masculino, 7 anos de idade, apresentando edema na região da mandíbula direita, dor a palpação, presença de abscesso periodontal com secreção purulenta na região do dente 85 e 46. Na tomografia computadorizada de feixe cônico (TCFC) mostrou imagem radiolúcida bem delimitada, expansiva e unilocular envolvendo a coroa e a bifurcação vestibular do elemento 46, rompendo a cortical óssea alveolar vestibular, compatível com Cisto da Bifurcação Vestibular. Concluiu-se que o cisto da bifurcação vestibular é uma doença pediátrica que ocorre na área de bifurcação da face vestibular de um primeiro molar inferior permanente em erupção e aparece principalmente na primeira década de vida.
The influence of parental style and socioeconomic circumstances on school bullying: A systematic review
Authors:   University of Ioannina, Greece., Tatiani Gkatsa
Published: May 2021

The phenomenon of school bullying is linked to family characteristics. The way in which parenting is exercised and the socioeconomic circumstances affect students’ involvement in school bullying for the victims and bully/victims, are reviewed. We conducted a systematic review of the published literature from 1982 until 2020 by using Google-Scholar, PsycINFO, Scopus and PubMed on the following words and phrases: “school bullying”, “parenting”, and “socioeconomic factors”. Prospective cohort, cross-sectional and meta-analytic studies were included. The review results showed that the quality of parental management and the inappropriate parental style, i.e. the authoritarian, the overprotective and the indifferent, influence negatively the students in bullying, in all roles. Also, the low socioeconomic level was associated with the involvement of students in school bullying in all roles. It was found that adverse economic conditions and low educational attainment they are correlated not only with the students involved in school bullying but also with the parenting style. In conclusion, important correlations between school bullying, parenting style and socio-economic conditions emerged. Keywords: School bullying, parental style, socioeconomic circumstances
THE BASICS ON ACCOUNTING PROFESSION SELECTION: LATEST CAPTURE DURING COVID-19 PANDEMIC ERA
Authors:   Universitas Wijaya Kusuma Surabaya Indonesia, Azizah Nurul , Purnamasari Fitri ,   Universitas Negeri Malang Indonesia
Published: May 2021

COVID-19 pandemic era is very potential in changing the mindset of students in the accounting field in seeing their future careers. It cannot be denied that there are several factors in how they view the prospects for the accounting profession amid this pandemic. This research was conducted at a university located in Malang City, Indonesia. The data was obtained through interviews with 70 students of the Accounting Department, Faculty of Economics. Interviews were conducted in person for approximately three months in 2020. In connection with the COVID-19 pandemic, interviews were conducted online. It is revealed that financial performance rewards and an ideal work environment are the two main factors that accounting students consider in determining their career path.
INTELLECTUAL CAPITAL, COMPETITIVE ADVANTAGE (EVIDENCE FROM INDONESIA’S MANUFACTURING SECTOR)
Authors:   Widya Mandala Surabaya Catholic University Indonesia, Merida Peggy Delita
Published: May 2021

The study aims to examine the direct relationship between intellectual capital and competitive advantage. The contribution of this paper is that there is a proxy competitive advantage the study was conducted on 444 manufacturing companies in Indonesia from 2013-2017. The novelty in this study is a research model that makes competitive advantage a dependent variable for intellectual capital and competitive advantage variables using market share proxy. The result of this study is intellectual capital has a positive effect on competitive advantage.
PENERAPAN METODE SCRAMBLE DALAM PEMBELAJARAN PENDIDIKAN AGAMA KRISTEN UNTUK MENINGKATKAN HASIL BELAJAR SISWA
Authors: Halawa Agnes Monica
Published: May 2021

Dalam proses pembelajaran guru sangat memerlukan metode sebagai sarana, teknik untuk penyampaian materi dan mencapai tujuan pembelajaran itu sendiri. Metode scramble salah satu metode pembelajaran yang menarik untuk diterapkan dalam proses pembelajaran khususnya pendidikan agama Kristen karena membantu konsentrasi dan kecepatan berpikir siswa dalam belajar.Tujuan dari penelitian ini dengan penerapan metode scramble peneliti ingin meningkatkan hasil belajar siswa pada mata pelajaran pendidikan agama kristen di SD Tunas Cemerlang, Jakarta Timur dengan jumlah 10 siswa Kristen diantaranya ada 4 siswa perempuan dan 6 siswa laki-laki. Pada penelitian ini peneliti menggunakan metode penelitian Tindakan Kelas (PTK) atau classroom action research, data hasil penelitian diperoleh berdasarkan hasil observasi nilai akhir semester siswa yang dilakukan dengan dua kali siklus dalam satu tahun pembelajaran atau satu siklus persemester.Dalam setiap siklus pada penelitian ini dilakukan dengan 4 langkah yaitu perencanaan, pelaksanaan, observasi atau pengamatan dan refleksi atau evaluasi. Penerapan metode scramble untuk peningkatan hasil belajar siswa dalam pembelajaran pendidikan agama Kristen diperoleh data hasil siklus I 50% siswa mampu berhasil mencapai hasil belajar yang sesuai dengan kriteria ketuntasan minimum dan data pada siklus II terlihat peningkatan dengan hasil 80% siswa berhasil mencapai hasil belajar di atas kriteria ketuntasan minimum di mata pelajaran pendidikan agama Kristen. Penerapan metode scramble dapat di terapkan dalam pembelajaran pendidikan agama Kristen untuk mencapai tujuan penelitian ini dalam meningkatkan hasil belajar, selain itu juga membantu meningkatkan aktivitas guru dan aktivitas siswa. Metode scramble juga membantu proses pembelajaran pendidikan agama Kristen menjadi tidak membosankan.
Antimicrobial Photodynamic Therapy: Molecular Cell Mechanisms and Prospects for Use in Dentistry
Authors: Kuvshinov A. V.
Published: May 2021

The article touches upon general issues of the course of photochemical reactions in biological systems and the mechanisms of such reactions during laser photodynamic therapy in dentistry. The properties and role of singlet oxygen, features of the response to photodynamic effects of gram-positive and gram-negative microorganisms, the spectrum and stages of the emergence of modern photosensitizers, and their disadvantages are reflected. On the basis of the information provided, as a conclusion, the main directions of the development of antimicrobial photodynamic therapy are formulated today.
Diminished Responsibility Post Codification: Lost Opportunities, Tensions and Gendered Applications
Authors: McPherson Rachel
Published: May 2021

Following from the Scottish Law Commission's Report on Insanity and Diminished Responsibility, the Criminal Justice and Licensing (Scotland) Act 2010 codified the plea of diminished responsibility. Part of the justification for this codification arose from the need to clarify the rule in relation to drugs and alcohol. With this change there existed scope to develop the plea in a way which appreciated the complex interplay between mental conditions and intoxication- something which was absent under common law. At a time when mental health law is under review in Scotland, this paper seeks to examine the landscape of diminished responsibility, asking whether s51B is able to properly appreciate the realities of offending and whether it is applied to all accused fairly and consistently.
The Characterisation And Water Equivalency Of Rhizophora Spp. Particleboard Bonded With Soy Protein
Authors: Rabaiee Nor Ain
Published: May 2021

The objective of this study was to explore the potential of particleboard made from a type of mangrove hardwood, i.e. Rhizophora spp., bonded with soy protein, and evaluate its suitability as a water-equivalent material. First, the bark of the raw hardwood was removed from its trunk prior to the grinding process. Next, three particleboards were fabricated with different percentages of soy protein (0 %, 8 %, and 16 %). The fabricated particleboards were each characterised for their density, mechanical properties, effective atomic number, morphological structure, elemental composition, and probability of photon interaction. The dimensional stability of each fabricated particleboard was evaluated according to the Japanese Industrial Standard (JIS) A 5908, Type-8, while the other properties were compared with that of the standard water phantom. There were improvements shown by the fabricated particleboards with 8 % and 16 % soy protein, in terms of dimensional stability. The morphological images also revealed that the particleboards bonded with 8 % and 16 % soy protein, have better contact between the particles, compared to the one bonded with 0 % soy protein. The elemental analysis, effective atomic number, and probability of photon interaction of the fabricated phantom showed identical results with that of the standard water phantom. Based on the findings of this study, the Rhizophora spp. particleboard bonded with soy protein has opened up possibilities for another potential alternative of solid phantom material as water-equivalent material.
The Competencies That School-Leavers Should Possess in Order to Meet the Challenges of the 21st Century
Authors: Pellaud Francine , Shankland Rebecca , Blandenier Gilles , Dubois Laurent , Gey Noémie , Massiot Philippe , Gay Philippe
Published: May 2021

The current state of the planet poses challenging ethical questions that shake up our emotions and values, thus making our choices and decisions more difficult. In order to grasp the many complex issues with which we are each confronted on a daily basis, education in sustainable development (ESD) advances competencies (Unesco, 2017) that are rooted in both cognitive and socio-emotional processes. Although ESD is included in most school curricula, it is worth exploring what teachers perceive to be the real needs for these thinking tools, as well as how they value the development of these competencies in school.This research, which was carried out with pre-service and in-service teachers, answers these two questions. These initial results bring to light the interdisciplinary nature of the competencies considered necessary by the teaching profession, as well as the strengths and weaknesses of the current school system with regard to their development. This interdisciplinary approach leads us to a definition of what a competence is with regard to the specificity of the school context, and finally, to propose a typology.We have used this typology to compare the visions of the teaching staff with the competency frameworks proposed by the international bodies with the most influence in the Swiss school system, namely the World Economic Forum, the OECD, and UNESCO. Comparisons between these different elements open up perspectives on what tools could be proposed for assessing these competencies in schools in the long term.
Selection for CD26− and CD49A+ Cells From Pluripotent Stem Cells-Derived Islet-Like Clusters Improves Therapeutic Activity in Diabetic Mice
Authors: Molakandov Kfir , Berti Denise A. , Beck Avital , Elhanani Ofer , Walker Michael D. , Soen Yoav , Yavriyants Karina , Zimerman Michal , Volman Ella , Toledo Itzik , Erukhimovich Anna , Levy Alon M. , Hasson Arik , Itskovitz-Eldor Joseph , Chebath Judith , Revel Michel
Published: May 2021

Background

Cell therapy of diabetes aims at restoring the physiological control of blood glucose by transplantation of functional pancreatic islet cells. A potentially unlimited source of cells for such transplantations would be islet cells derived from an in vitro differentiation of human pluripotent stem cells (hESC/hiPSC). The islet-like clusters (ILC) produced by the known differentiation protocols contain various cell populations. Among these, the β-cells that express both insulin and the transcription factor Nkx6.1 seem to be the most efficient to restore normoglycemia in diabetes animal models. Our aim was to find markers allowing selection of these efficient cells.

Methods

Functional Cell-Capture Screening (FCCS) was used to identify markers that preferentially capture the cells expressing both insulin and Nkx6.1, from hESC-derived ILC cells. In order to test whether selection for such markers could improve cell therapy in diabetic mouse models, we used ILC produced from a clinical-grade line of hESC by a refined differentiation protocol adapted to up-scalable bioreactors. Re-aggregated MACS sorted cells were encapsulated in microspheres made of alginate modified to reduce foreign body reaction. Implantation was done intraperitoneally in STZ-treated C57BL/6 immuno-competent mice.

Results

CD49A (integrin alpha1) was identified by FCCS as a marker for cells that express insulin (or C-peptide) as well as Nkx6.1 in ILC derived by hESC differentiation. The ILC fraction enriched in CD49A+ cells rapidly reduced glycemia when implanted in diabetic mice, whereas mice receiving the CD49A depleted population remained highly diabetic. CD49A-enriched ILC cells also produced higher levels of human C-peptide in the blood of transplanted mice. However, the difference between CD49A-enriched and total ILC cells remained small. Another marker, CD26 (DPP4), was identified by FCCS as binding insulin-expressing cells which are Nkx6.1 negative. Depletion of CD26+ cells followed by enrichment for CD49A+ cells increased insulin+/Nkx6.1+ cells fraction to ~70%. The CD26-/CD49A+ enriched ILC exhibited improved function over non-sorted ILC or CD49A+ cells in diabetic mice and maintain prolonged blood C-peptide levels.

Conclusions

Refining the composition of ILC differentiated from hPSC by negative selection to remove cells expressing CD26 and positive selection for CD49A expressing cells could enable more effective cell therapy of diabetes.
BTOB: Extending the Biased GWAS to Bivariate GWAS
Authors: Zhu Junxian , Fan Qiao , Deng Wenying , Wang Yimeng , Guo Xiaobo
Published: May 2021

In recent years, a number of literatures published large-scale genome-wide association studies (GWASs) for human diseases or traits while adjusting for other heritable covariate. However, it is known that these GWASs are biased, which may lead to biased genetic estimates or even false positives. In this study, we provide a method called “BTOB” which extends the biased GWAS to bivariate GWAS by integrating the summary association statistics from the biased GWAS and the GWAS for the adjusted heritable covariate. We employ the proposed BTOB method to analyze the summary association statistics from the large scale meta-GWASs for waist-to-hip ratio (WHR) and body mass index (BMI), and show that the proposed approach can help identify more susceptible genes compared with the corresponding univariate GWASs. Theoretical results and simulations also confirm the validity and efficiency of the proposed BTOB method.
The Fractalkine Receptor CX3CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling
Authors: Spray Luke , Park Catherine , Cormack Suzanne , Mohammed Ashfaq , Panahi Pedram , Boag Stephen , Bennaceur Karim , Sopova Kateryna , Richardson Gavin , Stangl Verena M. , Rech Lavinia , Rainer Peter P. , Ramos Gustavo Campos , Hofmann Ulrich , Stellos Konstantinos , Spyridopoulos Ioakim
Published: May 2021

Aims

Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).

Methods and Results

We retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling.

Conclusion

We show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.
Profile of Circulatory Cytokines and Chemokines in Human Coronaviruses: A Systematic Review and Meta-Analysis
Authors: Zawawi Ayat , Naser Abdallah Y. , Alwafi Hassan , Minshawi Faisal
Published: May 2021

Background

SARS, MERS, and COVID-19 share similar characteristics. For instance, the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50%, respectively, which may cause similar clinical features. Moreover, uncontrolled release of proinflammatory mediators (also called a cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 patients leads to severe phenotype development.

Aim

This systematic review and meta-analysis aimed to evaluate the inflammatory cytokine profile associated with three strains of severe human coronavirus diseases (MERS-CoV, SARS-CoV, and SARS-CoV-2).

Method

The PubMed, Embase, and Cochrane Library databases were searched for studies published until July 2020. Randomized and observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV, and SARS-CoV-2, were included. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval to estimate the pooled mean of inflammatory biomarkers.

Results

A high level of circulating IL-6 could be associated with the severity of infection of the three coronavirus strains. TNF, IL-10, and IL-8 are associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS.

Conclusion

This study suggests that the immune response and immunopathology in the three severe human coronavirus strains are somewhat similar. The findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6. This could be used as a potential therapeutic target to improve patients’ outcomes in severe cases.

Systematic Review Registration

PROSPERO registration 94 number: CRD42020209931.
The Mean Vertigo Score (MVS) Outcome Scale and Its Use in Clinical Research for Quantifying Vestibular Disorders
Authors: Rahlfs Volker W. , Zimmermann Helmuth
Published: May 2021

Introduction: The Mean Vertigo Score (MVS) is a composite score for defining the burden of disease of patients suffering from vestibular disorders. It has been used in clinical research for about 30 years. This study investigates discriminant validity of the MVS and describes structural relationships of the 12 single criteria used for construction of the MVS.

Materials and Methods: The statistical analyses are based on the raw data of an earlier conducted randomized, doubleblind, placebo-controlled clinical trial, which compared the following four randomized treatment groups: a fixed combination of cinnarizine and dimenhydrinate (Arlevert), two groups with only one of the two study drugs, and a group with placebo. The method used for the statistical calculations is the Wei-Lachin procedure, a multivariate generalization of the Mann-Whitney test, which takes into account correlations among the 12 single symptoms of the composite score.

Results: All 12 single symptoms of the composite endpoint proved to be useful for detecting differences (Mann-Whitney effect size measures: 0.58–0.73) and thus for discriminating between treatment groups. Their Pearson product-moment correlations are all positive (range 0.07–0.71) and point to the same direction, which indicates one-dimensionality and good internal consistency of the composite index MVS. Furthermore, our statistical calculations revealed that successively increasing the number of single items of the MVS to up to twelve enhances its reliability (R12 = 0.923), which leads to a substantially higher test power and reduction of the number of patients needed (sample size) in a clinical trial.

Conclusion: The use of the multivariate Wei-Lachin procedure provides further evidence of the validity of the 12-item composite score MVS, based on the efficacy data of its 12 single vertigo symptoms. The present findings demonstrate that the MVS is a powerful tool, which can be used to adequately describe the patients' self-perceived vertigo complaints, both qualitatively and quantitatively. It may therefore be regarded as a clinically meaningful alternative to other questionnaires that are presently used in vestibular research.
Circulating hsa-miR-323b-3p in Huntington's Disease: A Pilot Study
Authors: Ferraldeschi Michela , Romano Silvia , Giglio Simona , Romano Carmela , Morena Emanuele , Mechelli Rosella , Annibali Viviana , Ubaldi Martina , Buscarinu Maria Chiara , Umeton Renato , Sani Gabriele , Vecchione Andrea , Salvetti Marco , Ristori Giovanni
Published: May 2021

The momentum of gene therapy in Huntington's disease (HD) deserves biomarkers from easily accessible fluid. We planned a study to verify whether plasma miRNome may provide useful peripheral “reporter(s)” for the management of HD patients. We performed an exploratory microarray study of whole non-coding RNA profiles in plasma from nine patients with HD and 13 matched controls [eight healthy subjects (HS) and five psychiatric patients (PP) to minimize possible iatrogenic impact on the profile of non-coding RNAs]. We found an HD-specific signature: downregulation of hsa-miR-98 (fold change, −1.5, p = 0.0338 HD vs. HS, and fold change, 1.5, p = 0.0045 HD vs. PP) and upregulation of hsa-miR-323b-3p (fold change, 1.5, p = 0.0007 HD vs. HS, and fold change, 1.5, p = 0.0111 HD vs. PP). To validate this result in an independent cohort, we quantify by digital droplet PCR (ddPCR) the presence of the two microRNA in the plasma of 33 HD patients and 49 matched controls (25 HS and 24 PP patients). We were able to confirm that hsa-miR-323b-3p was upregulated in HD and premanifest HD vs. HS and PP: the median values (first–third quartile) were 4.1 (0.9–10.53) and 5.8 (1.9–10.70) vs. 0.69 (0.3–2.75) and 1.4 (0.78–2.70), respectively, p < 0.05. No significant difference was found for hsa-miR-98. To evaluate the biological plausibility of the hsa-miR-323b-3p as a component of the disease pathophysiology, we performed a bioinformatic analysis based on its targetome and the huntingtin (HTT) interactome. We found a statistically significant overconnectivity between the targetome of hsa-miR-323b-3p and the HTT interactome (p = 1.48e−08). Furthermore, there was a significant transcription regulation of the HTT interactome by the miR-323b-3p targetome (p = 0.02). The availability of handy, reproducible, and minimally invasive biomarkers coming from peripheral miRNome may be valuable to characterize the illness progression, to indicate new therapeutic targets, and to monitor the effect of disease-modifying treatments. Our data deserve further studies with larger sample size and longitudinal design.
Cardiac Structure and Function Is Associated With Hemispatial Neglect Severity
Authors: Williams Nicole L. , Suarez Adrian , Negoita Serban , Hillis Argye E. , Gottesman Rebecca F. , Johansen Michelle C.
Published: May 2021

Background: Hemispatial neglect is a debilitating consequence of right hemispheric ischemic stroke (RIS), with evidence that patient-level factors influence neglect severity. Study objective: Determine if cardiac function is associated with presence and severity of neglect, independent of infarct size.

Methods: Two hundred and eighteen non-demented, RIS with cerebral MRI and echocardiography who completed ≥1 of 4 tests evaluating neglect were included. Age- and sex- adjusted Z-scores defined neglect with severity categorized as no neglect, neglect on one or neglect on ≥2 tests. The dependent variable was presence of neglect (multivariable logistic regression), or neglect severity (multinomial logistic regression). The association with left ventricular (LV) structure/function (independent variable) was evaluated using separate nested adjustment models.

Results: Patients were on average 61 yo (21–95), female (50%), black (53%), with an ejection fraction of 60% (IQR 20–75%). Fifty eight (27%) had neglect. Each 1 cm increase in LV systolic diameter was associated with a higher relative risk of having neglect on two tests compared to those with no neglect (RRR = 1.83, 95% CI 1.01–3.32), but not after adjusting for education and DWI volume (RRR = 1.68, 95% CI 0.89–3.19). Per 1 cm increase in left atrial (LA) diameter, the relative risk of having neglect on 2 tests vs. no neglect was over two times higher (95% CI 1.04–4.77), but lost significance in the final model (RRR = 1.73, 95% CI 0.76–3.94).

Conclusions: We found an association between markers of diastolic dysfunction (enlarging LV, compensatory enlarging LA) and severity of neglect, suggesting that cardiac structure, and function affects not only lesion volume, but also the functional consequences of infarct volume.
Impact of COVID-19 Pandemic on Intervals and Outcomes of Repeated Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma
Authors: Jin Zhi-Cheng , Chen Li , Zhong Bin-Yan , Zhu Hai-Dong , Zeng Chu-Hui , Li Rui , Guo Jin-He , He Shi-Cheng , Deng Gang , Zhu Xiao-Li , Ni Cai-Fang , Teng Gao-Jun
Published: May 2021

Purpose

Given that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution’s ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients.

Materials and Methods

This retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals.

Results

The median follow-up interval was 82.0 days (IQR, 61–109) in the study group, which was significantly longer than 66.0 days (IQR, 51–94) in the control group (P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively (P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040–5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022–6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797–3.480; P <0.001) were independent predictors for the efficacy of TACE treatment.

Conclusions

The COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis.
Antibody Format and Serum Disposition Govern Ocular Pharmacokinetics of Intravenously Administered Protein Therapeutics
Authors: Shivva Vittal , Boswell C. Andrew , Rafidi Hanine , Kelley Robert F. , Kamath Amrita V. , Crowell Susan R.
Published: May 2021

Protein therapeutics have witnessed tremendous use and application in recent years in treatment of various diseases. Predicting efficacy and safety during drug discovery and translational development is a key factor for successful clinical development of these therapies. In general, drug related toxicities are predominantly driven by pharmacokinetic (PK) exposure at off-target sites. This work explores the ocular PK of intravenously administered protein therapeutics to understand impact of antibody format on off-site exposure. Species matched non-binding rabbit antibody proteins (rabFab and rabIgG) were intravenously administered to male New Zealand White rabbits at a single 1 mg bolus dose and exposure was measured up to 3 weeks. As anticipated based on absence of FcRn recycling, rabFab has relatively fast systemic PK (CL–943 mL/day and t1/2–1.93 days) compared to rabIgG (CL–18.5 mL/day and t1/2–8.93 days). Similarly, rabFab has lower absolute ocular exposure in ocular compartments (e.g., vitreous and aqueous humor) compared to rabIgG, despite higher relative exposures (measured as percent tissue partition in ocular tissues relative to serum, based on Cmaxand AUC). In general, percent tissue partition based on AUC (in aqueous and vitreous humor) relative to serum exposure were 10.4 and 8.62 for rabFab respectively and 1.11 and 0.64 for rabIgG respectively. This work emphasizes size and format based ocular exposure of intravenously administered protein therapeutics. Findings from this work enable prediction of format based ocular exposure for systemically administered antibody based therapeutics and aid in selection of molecule format for clinical candidate to minimize ocular exposure.
Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitor in Combination with Angiotensin-Receptor Blocker in Chronic Kidney Disease Based on Dose: A Systematic Review and Meta-Analysis
Authors: Zhao Mingming , Wang Rumeng , Yu Yi , Chang Meiying , Ma Sijia , Zhang Hanwen , Qu Hua , Zhang Yu
Published: May 2021

Background: The purpose of this meta-analysis was to evaluate the controversy of angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) in the treatment of chronic kidney disease (CKD) based on dose.

Methods: PubMed, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) from inception to March 2020. The random effects model was used to calculate the effect sizes. Potential sources of heterogeneity were detected using sensitivity analysis and meta-regression.

Results: This meta-analysis of 53 RCTs with 6,375 patients demonstrated that in patients with CKD, ACEI in combination with ARB was superior to low-dose ACEI or ARB in reducing urine albumin excretion (SMD, −0.43; 95% CI, −0.67 to −0.19; p = 0.001), urine protein excretion (SMD, −0.22; 95% CI, −0.33 to −0.11; p < 0.001), and blood pressure (BP), including systolic BP (WMD, −2.89; 95% CI, −3.88 to −1.89; p < 0.001) and diastolic BP (WMD, −3.02; 95% CI, −4.46 to −1.58; p < 0.001). However, it was associated with decreased glomerular filtration rate (GFR) (SMD, −0.13; 95% CI, −0.24 to −0.02; p = 0.02) and increased rates of hyperkalemia (RR, 2.07; 95% CI, 1.55 to 2.76; p < 0.001) and hypotension (RR, 2.19; 95% CI, 1.35 to 3.54; p = 0.001). ACEI in combination with ARB was more effective than high-dose ACEI or ARB in reducing urine albumin excretion (SMD, −0.84; 95% CI, −1.26 to −0.43; p < 0.001) and urine protein excretion (SMD, −0.24; 95% CI, −0.39 to −0.09; p = 0.002), without decrease in GFR (SMD, 0.02; 95% CI, −0.12 to 0.15; p = 0.78) and increase in rate of hyperkalemia (RR, 0.94; 95% CI, 0.65 to 1.37; p = 0.76). Nonetheless, the combination did not decrease the BP and increased the rate of hypotension (RR, 3.95; 95% CI, 1.13 to 13.84; p = 0.03) compared with high-dose ACEI or ARB.

Conclusion: ACEI in combination with ARB is superior in reducing urine albumin excretion and urine protein excretion. The combination is more effective than high-dose ACEI or ARB without decreasing GFR and increasing the incidence of hyperkalemia. Despite the risk of hypotension, ACEI in combination with ARB is a better choice for CKD patients who need to increase the dose of ACEI or ARB (PROSPERO CRD42020179398).
Validation of an Instrument for Measuring Adherence to Treatment With Immunomodulators in Patients With Multiple Myeloma
Authors: Silveira Lívia Pena , Menezes de Pádua Cristiane Aparecida , Drummond Paula Lana de Miranda , Malta Jéssica Soares , Marques dos Santos Roberta Márcia , Costa Naiane Lima , Machado Taísa Roberta Lopes , Reis Adriano Max Moreira
Published: May 2021

Background: Validate the Treatment Adherence Measure (TAM) instrument in outpatients with MM concerning construct validity, reliability and the ceiling and floor effects.

Methods: This cross-sectional study included patients diagnosed with MM previously treated with an immunomodulator for at least one month, aged 18 or over, and followed-up in the investigated outpatient clinics. Adherence to immunomodulators was measured by TAM. The TAM’s reliability was assessed using Cronbach’s alpha; The association between adherence and health-related quality of life was investigated to analyze the divergent and convergent construct, measured by the Quality of Life Questionnaire core (QLQ-C30) and the Quality of Life Questionnaire Multiple Myeloma module (QLQ-MY20). The presence of a ceiling or floor effect in the TAM was also analyzed.

Results: Eighty-four patients were included in the study, achieving 97.6% adherence. Cronbach’s alpha was 0.41, and the hypothesis of convergent construct validity was confirmed, with statistical significance, in contrast to the hypothesis of divergent construct validity. The presence of the ceiling effect in TAM suggested that this instrument does not allow changes to be detected in individuals concerning adherence to IMiDs.

Conclusion: TAM instrument did not show satisfactory validity and reliability to measure MM’s adherence. MM patients treated at oncohematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to IMiDs.
The Defense Response Involved in Sweetpotato Resistance to Root-Knot Nematode Meloidogyne incognita: Comparison of Root Transcriptomes of Resistant and Susceptible Sweetpotato Cultivars With Respect to Induced and Constitutive Defense Responses
Authors: Lee Il-Hwan , Kim Ho Soo , Nam Ki Jung , Lee Kang-Lok , Yang Jung-Wook , Kwak Sang-Soo , Lee Jeung Joo , Shim Donghwan , Kim Yun-Hee
Published: May 2021

Sweetpotato (Ipomoea batatas [L.] Lam) is an economically important, nutrient- and pigment-rich root vegetable used as both food and feed. Root-knot nematode (RKN), Meloidogyne incognita, causes major yield losses in sweetpotato and other crops worldwide. The identification of genes and mechanisms responsible for resistance to RKN will facilitate the development of RKN resistant cultivars not only in sweetpotato but also in other crops. In this study, we performed RNA-seq analysis of RKN resistant cultivars (RCs; Danjami, Pungwonmi and Juhwangmi) and susceptible cultivars (SCs; Dahomi, Shinhwangmi and Yulmi) of sweetpotato infected with M. incognita to examine the induced and constitutive defense response-related transcriptional changes. During induced defense, genes related to defense and secondary metabolites were induced in SCs, whereas those related to receptor protein kinase signaling and protein phosphorylation were induced in RCs. In the uninfected control, genes involved in proteolysis and biotic stimuli showed differential expression levels between RCs and SCs during constitutive defense. Additionally, genes related to redox regulation, lipid and cell wall metabolism, protease inhibitor and proteases were putatively identified as RKN defense-related genes. The root transcriptome of SCs was also analyzed under uninfected conditions, and several potential candidate genes were identified. Overall, our data provide key insights into the transcriptional changes in sweetpotato genes that occur during induced and constitutive defense responses against RKN infection.