bluuebunny/crossref_metadata_2025 huggingface dataset:
Financiamento, Composição dos Gastos e Eficiência na Saúde dos Municípios Pernambucanos
Authors: Sousa Kleber Morais de , Pinhanez Monica de Maria Santos Fornitani , Monte Paulo Aguiar do , Cavalcante Paulo Roberto Nóbrega
Published: July 2020

Este trabalho teve por objetivo investigar a influência do financiamento e da composição do gasto público na eficiência da produção dos serviços de saúde dos municípios do Estado de Pernambuco. A pesquisa foi realizada em dois estágios. O primeiro estágio mensurou a eficiência e o segundo analisou a eficiência frente as variáveis financeiras e de controle por meio de regressão múltipla com dados em painel e efeitos fixos. A amostra do estudo foi formada pelos 184 municípios pernambucanos e os dados compreenderam o período de 2011 a 2015. Os resultados evidenciaram que a população com idade superior a 65 anos influencia negativamente na eficiência dos serviços de saúde dos municípios, enquanto o gasto com pessoal em saúde, o gasto com investimento em saúde, a despesa em saúde financiada com recursos do SUS e a despesa em saúde financiada com recursos de impostos influenciam positivamente na eficiência.
Rekayasa dan Penguatan Lembaga Menghadapi Persaingan Global Berbasis Wirausaha dan Etika Islam
Authors: Madjakusumah Deden Gandana , Saripudin Udin , Suryani Suryani
Published: July 2020

Abstract: The economic trends of countries in the world tend to lead to globalization and several countries that have a common interest in forming a global place in a narrower or regional scope such as AFTA, APEC, NAFTA, and so on are the efforts of countries that are members of these organizations. to be able to compete in the global economy. This paper aims to elaborate the concept of engineering and strengthening of entrepreneurial institutions and Islamic ethics in order to face the era of the global market. This study uses the literature study method, namely by studying various sources and literature related to institutional strengthening, entrepreneurship, and Islamic ethics. The results of the study concluded that organizational development as an engineering and strengthening of institutions to improve global competitiveness based on entrepreneurship and Islamic ethics can be an alternative solution for government, private and community institutions in facing competition between institutions that demand that each institution can have a competitive advantage and make values entrepreneurship and Islamic ethics as a basis in Engineering and Strengthening Institutions to enhance global competitiveness.Abstrak: Tren perekonomian negara-negara di dunia cenderung  mengarah kepada globalisasi dan beberapa negara yang memiliki kesamaan kepentingan membentuk satu tempat global pada ruang lingkup yang lebih sempit atau regional seperti AFTA, APEC, NAFTA, dan sebagainya merupakan upaya dari negara-negara yang tergabung dalam organisasi tersebut untuk tetap dapat bersaing dalam kancah perekonomian global. Tulisan ini bertujuan untuk mengelaborasi konsep rekayasa dan penguatan lembaga berbasis kewirausahaan dan etika Islam dalam rangka menghadapi era pasar global. Kajian ini menggunakan metode kajian pustaka, yakni dengan mempelajari berbagai sumber dan literature yang terkait dengan penguatan lembaga, kewirausahaan, dan etika Islam. Hasil kajian menyimpulkan bahwa pengembangan organisasi sebagai rekayasa dan penguatan lembaga untuk meningkatkan daya saing global berbasis wirausaha dan etika Islam dapat menjadi alternatif solusi bagi lembaga-lembaga pemerintahan, swasta dan masyarakat dalam menghadapi persaingan antar lembaga yang menuntut setiap lembaga dapat memiliki keunggulan kompetitif dan menjadikan nilai-nilai wirausaha serta etika Islam sebagai basis dalam rekayasa dan penguatan lembaga untuk meningkatkan daya saing global.
The Modus of Beggars in Lampung Urban Area : An Islamic Law Perspective
Authors: Abror Khoirul , Suhairi Suhairi , Ja'far A. Kumedi
Published: July 2020

The poor and underprivileged are people who must be considered by the Government, but the reality at this time is that there are many poor and underprivileged people who become professions in the city of Bandar Lampung and Metro City, so it is necessary to review the existence and factors that influence it. This review is a field research (field research) conducted in Bandar Lampung City and Metro City; by describing data obtained through observation, in-depth interviews; the method used in analyzing is qualitative analysis presented descriptively; the aim is to find factors that drive the existence of beggars in urban areas, and the mode used by urban beggars. The existence of beggars in the city of Bandar Lampung and the city of Metro both at the intersection of red lights and in the mall yard, the courtyard of the mosque and the home visit is a mode to get easy income, the main factor that drives the existence of beggars in the city of Bandar Lampung and Metro City due to income that is not fulfilling the necessities of life, the attractiveness factor of work that is easy, practical, influenced by the sympathies of potential benefactors, and relatively large income; various modes undertaken by beggars to attract the sympathy of the community, including bringing children who are still toddlers, pretending to be blind and lame, employing elderly parents (elderly), dressing all worn out, and pretending to smear that does not heal ; The existence of beggars in the city of Bandar Lampung and the city of Metro both at the intersection of red lights and in the mall yard, the courtyard of the mosque and the home visit is a mode to get easy income, the main factor that drives the existence of beggars in the city of Bandar Lampung and Metro City due to income that is not fulfilling the necessities of life, the attractiveness factor of work that is easy, practical, influenced by the sympathies of potential benefactors, and relatively large income; various modes undertaken by beggars to attract the sympathy of the community, including bringing children who are still toddlers, pretending to be blind and lame, employing elderly parents (elderly), dressing all worn out, and pretending to smear that does not heal.
The New Fiqh in A National School of Legal Thought: A Paradigm Shift in National School of Islamic Law on M. Barry Hooker’s Perspective
Authors: Hefni Wildani
Published: July 2020

The polemic of the domain between religious regulation and state authority in the national school of Islamic law in Indonesia seems to be endlessly debated by Indonesian and Western Scholars, Muslim as well as non-muslims. This article discusses western scholarly discourses on the National School of Islamic law by examining the thoughts and works from M. Barry Hooker. Hooker introduced the term “new fiqh” in the national school of Islamic discourse and explained that the Indonesian fiqh instrumentalized by the state. Based on the model of the study of public figures and grounded its main data of Hooker’s work, this paper shows that Hooker criticizes the shifting paradigm of classical fiqh text to fiqh dominated by the state. The state determines the process of fiqh with various instruments and public transmission of sharia, including religious bureaucratization, state intervention in Islamic legal education curriculum, and through religious pulpit mediums.Fikih mazhab nasional mengemuka dalam perebutan domain antara peraturan agama dan otoritas negara. Diskursus ini menjadi perdebatan baik di kalangan sarjana Indonesia maupun sarjana di Barat. Tulisan ini mengkaji diskursus hukum Islam mazhab nasional yang dikenal dengan istilah fikih baru dari seorang intelektual di Barat bernama M. Barry Hooker. Hooker memandang fikih Indonesia saat ini merupakan fikih yang dibentuk dan diinstrumentalisasi oleh negara. Dengan menggunakan model kajian pemikiran tokoh serta karya kesarjanaannya, tulisan ini menunjukkan bahwa Hooker memiliki pandangan yang kritis dengan mengungkap pergeseran dari fikih klasik yang didasarkan pada teks keagamaan kearah fikih mazhab nasional dengan dominasi peran negara. Negara menjadi penentu proses perjalanan fikih dengan pelbagai instrumen yang diberikan pada masyarakat, antara lain birokratisasi agama, intervensi negara dalam kurikulum pendidikan hukum Islam, dan melalui medium mimbar keagamaan.
O papel do gênero social nos estudos sociolinguísticos: desafios metodológicos na análise do futuro variável
Authors: Clempi Camila Bordonal , Rodrigues Angélica
Published: July 2020

Tendo em vista o tratamento subalterno de investigação da variável gênero enquanto uma categoria fluída de construção e identificação social, histórica e cultural nos estudos sociolinguísticos, objetivamos, neste artigo, discutir os principais desafios metodológicos e apresentar as possibilidades de análise do papel feminino na mudança linguística, mais especificamente na mudança das formas verbais para expressão de tempo futuro no português brasileiro escrito, à luz dos preceitos teóricos e metodológicos da Sociolinguística e da Teoria da Variação e Mudança (WEINREICH; LABOV; HERZOG, 2006 [1968]; LABOV, 2016 [1972]).
Ferdinand de Saussure: relações possíveis entre a língua e a história
Authors: Henriques Stefania Montes , Coelho Micaela Pafume
Published: July 2020

Neste trabalho, partimos da análise de alguns documentos de Ferdinand de Saussure para propor relações possíveis entre a língua e a história. A busca por estabelecer essas relações se justifica na medida em que, constantemente, o conceito saussuriano de língua é tomado como um elemento isolado dos fenômenos sociais, sendo entendido como um objeto de estudo que se constitui unicamente a partir de uma abstração. Considerando isso, hipotetizamos que essas críticas se estabelecem, pois desconsideram que, para Saussure, além de ser um sistema de signos, a língua é, também, uma instituição social, que apresenta uma relação necessária com os fenômenos sociais que constituem a história. A partir dessa hipótese, mostramos que tanto a história da língua, como a história dos povos se mostram relevantes para a conceituação de língua apresentada nos documentos de Saussure fontes de nosso trabalho.
50 anos do GEL: caminhos da linguística no Brasil
Authors: Coelho Olga Ferreira
Published: July 2020

Neste artigo, são analisados 4108 artigos publicados nas revistas do GEL entre 1993 e 2018, com o objetivo de oferecer um perfil da produção linguística em circulação no Grupo. Além disso, se apresenta um conjunto de propostas para o futuro do GEL. O perfil e as propostas foram elaborados em consonância com princípios da Historiografia Linguística.
O processo de internacionalização e o ensino e aprendizagem de língua inglesa no contexto de uma universidade estadual
Authors: Kaneko Marques Sandra Mari , Baffi Bonvino Melissa Alves
Published: July 2020

A partir de conceitos de internacionalização e proficiência em língua estrangeira, objetivamos, neste artigo, mapear dados sobre os níveis de proficiência obtidos por aprendizes advindos de projetos de ensino de língua inglesa, com financiamento e parcerias externas, que vêm sendo desenvolvidos em uma universidade pública paulista. No âmbito desses projetos, são oferecidos cursos e testes de nivelamento on-line para alunos de graduação, pós-graduação e servidores. Os cursos ocorrem na modalidade on-line, utilizando a ferramenta de webconferência Zoom. Os professores atuantes em tais cursos são alunos de graduação e pós-graduação em Letras, orientados por especialistas em formação de professores, tecnologias no ensino de línguas e avaliação.
Análise quantitativa dos dados para um protótipo de dicionário semibilíngue de expressões idiomáticas
Authors: Euzébio Natália Gabrieli dos Santos Fagundes
Published: July 2020

Considerando as expressões idiomáticas como estruturas léxicas complexas, polilexicais, de sentido figurado e cristalizadas pela tradição cultural de um povo (XATARA, 1998), este trabalho tem como objetivo apresentar uma amostra das expressões levantadas até o momento e a análise quantitativa parcial dos dados em língua portuguesa coletados em uma pesquisa de mestrado, ainda em desenvolvimento, que visa à elaboração de um protótipo de dicionário semibilíngue de expressões idiomáticas, sob um olhar Fraseodidático. Tem-se como base os princípios teóricos da Fraseologia oferecidos por Tristá Perez (1988) e Montoro del Arco (2006), da Fraseografia por Olímpio de Oliveira Silva (2007), da Lexicologia por Biderman (2001) e da Lexicografia por Haensch (1982) e Porto Dapena (2002). O desenvolvimento da pesquisa realiza-se sob o ponto de vista metodológico da Linguística de Corpus (SARDINHA, 2000; TAGNIN, 2011), por meio da elaboração de um corpus de textos jornalísticos do caderno de esporte, jornal digital Estadão e pretende a elaboração de um material que auxilie professores e aprendizes de nível inicial da língua espanhola.
Da elaboração de um glossário colaborativo à discussão sobre os termos “inglês para aviação” e “inglês aeronáutico”
Authors: Tosqui-Lucks Patricia , Silva Ana Lígia Barbosa de Carvalho e
Published: July 2020

Neste artigo discutimos a necessidade de harmonização de termos na área de aviação, apresentamos aspectos teóricos e metodológicos empregados na elaboração de um glossário bilíngue colaborativo de inglês aeronáutico e, por fim, realizamos a discussão de dois termos fundamentais não só ao glossário, mas à área de aviação em si: “inglês para aviação” e “inglês aeronáutico”, justificando a necessidade de diferenciação dos dois termos.
Controvérsias na patologização e contradiscursos na afasia e na infância
Authors: Coudry Maria Irma Hadler
Published: July 2020

O objetivo do texto é dar continuidade ao estudo da relação entre afasia e linguagem infantil, analisando, por um lado, controvérsias disponíveis na Internet sobre afasia e infância, e propondo, por outro, contradiscursos para avaliar e acompanhar afásicos e crianças com dificuldade de entrar na leitura/escrita. Os dados de fala e escrita, de afásicos e crianças, confirmam a hipótese clássica de Roman Jakobson e mostram que o encontro entre afasia e linguagem infantil se dá nos vários níveis de análise linguística, guiado pelo sentido e pelo contexto discursivo. Por fim, apresentamos experimentos com a linguagem, específicos para as modificações da linguagem na afasia e para crianças às voltas com a patologização, logo em sua escrita inicial.
Grau de auxiliaridade da microconstrução [deixar+de+V2inf.] no português arcaico
Authors: Prezotto Júnior José Roberto
Published: July 2020

Propomos investigar, com base na abordagem construcional (TRAUGOTT; TROUSDALE, 2013), a microconstrução aspectual [deixar+de+V2inf.] no português arcaico (séculos XIII-XV). Para análise, utilizamos o Corpus do Português (DAVIS; FERREIRA, 2006, 2016) e cotejamos parâmetros fundamentados nos estudos clássicos de verbo auxiliar. No período estudado, a microconstrução, sob a forma [leixar+de+V2inf.], apresenta índices de auxiliaridade e marca aspecto final (terminativo e cessativo). Além disso, ela é parcialmente esquemática, pela recorrência de elementos entre seus componentes, parcialmente produtiva, por ainda estar expandindo seus arranjos colocacionais, e não composicional, pela codificação de seus elementos como um chunk procedural.
O projeto Bruxas Paulistas e a edição de processos eclesiásticos
Authors: Módolo Marcelo
Published: July 2020

O Projeto Bruxas Paulistas constitui-se de um conjunto de treze processos eclesiásticos do século XVIII, fonte de pesquisa rica e pouco explorada de um trecho de nossa história ainda sombrio e pouco conhecido: a atuação indireta do Tribunal do Santo Ofício na região sudeste do Brasil. Igualmente, segundo Fernandes (2012), tais processos podem trazer uma significativa representação da língua falada para épocas pretéritas, captando variações já perceptíveis na oralidade, dada a preocupação do escrivão em registrar depoimentos ipsis litteris e com rapidez. A pesquisa ratifica, portanto – pela análise do processo de Santa Joana Gil – a importância de transcrever filologicamente essa documentação para se conhecer melhor a história desse período colonial brasileiro e resgatar possíveis indícios de variação e mudança linguística ocorridos no século XVIII.
A expressão de condicionalidade na construção [caso + oração finita] no português do Brasil
Authors: Silva Camila Fernandes da
Published: July 2020

Considerando que na categoria condicional encontra-se uma variedade de estruturas que podem expressar diferentes nuances de condicionalidade, busca-se compreender como traços da estrutura formal e aspectos semântico-pragmáticos da construção [caso + oração finita] se relacionam para compor o significado condicional. Sob a perspectiva dos modelos baseados no uso, nossos pressupostos teóricos baseiam-se, especialmente, em Dancygier (1998) e Dancygier e Sweetser (2005). Os dados correspondem ao português brasileiro contemporâneo (séculos XX e XXI), extraídos do Corpus do Português.
As dificuldades de encontrar palavras: entre o som e o significado
Authors: Oliveira Marcus Vinicius Borges
Published: July 2020

A sensação de ausência ou inacessibilidade de uma palavra que desejamos encontrar é referida na literatura científica pela sigla WFD (Word Finding Difficulties), fenômeno presente tanto na normalidade quanto em algumas patologias que impactam o funcionamento da linguagem. O objetivo deste artigo é discutir criticamente a autonomia dos níveis linguísticos a partir de dados emergentes no campo das afasias. A metodologia utilizada compreende a análise microgenética de enunciados produzidos por uma senhora afásica, em contextos dialógicos. Tomando como base a Neurolinguística de orientação enunciativo-discursiva, a reflexão integra três campos de investigação científica, dentre os quais tem especial relevância a Linguística desenvolvida por Jakobson. Baseamo-nos também na Neuropsicologia Luriana e na Filosofia da Linguagem desenvolvida pelo Círculo de Bakhtin. Os dados apresentados e analisados deixam entrever, a partir do conceito de indissociabilidade entre som e sentido, a interdependência dos níveis linguísticos e, indo além, da multidimensionalidade presente na rede de enlaces que está subjacente a cada palavra.
Construções subordinadas com o verbo saber em uma perspectiva cognitivo-funcional
Authors: Bertasso Flavia do Carmo
Published: July 2020

O objetivo deste trabalho é investigar o funcionamento de diferentes construções com o verbo saber, sob o aparato teórico da Linguística Cognitiva, especialmente Langacker (1987, 1991, 2009). A partir de dados do português falado no interior paulista, busca-se descrever os usos do verbo saber em contextos de complementação oracional com o propósito de determinar quais são suas formas e funções na variedade do português investigada. Os resultados mostram que o verbo saber: (i) no uso com função textual-interativa, é encontrado mais vezes na terceira pessoa do singular, no presente do indicativo e em posição final na oração, e (ii) no uso como matriz de oração completiva, o verbo é mais utilizado na primeira pessoa do singular, no presente do indicativo e em posição inicial na oração.
Investigando efeito retroativo do SAEB/Prova Brasil de leitura no 9º ano do ensino fundamental
Authors: Barbosa Adriana de Oliveira
Published: July 2020

Neste artigo apresento resultados parciais de uma investigação qualitativa sobre o efeito retroativo de uma avaliação padronizada em larga escala presente no contexto educacional brasileiro, o SAEB/Prova Brasil. Foram conduzidas entrevistas semiestruturadas com gestores e professores de 9º ano de língua portuguesa de duas escolas e um centro regional de ensino do Distrito Federal e analisadas suas percepções acerca dessa avaliação, com o objetivo de contribuir para a compreensão do fenômeno do efeito retroativo. Os resultados encontrados trazem reflexões pertinentes acerca da avaliação pelos entrevistados, que não a ignoram e revelam algumas estratégias adotadas por força da avaliação em uma das escolas, dando indícios de efeito retroativo de intensidade fraca, ligado ao fator de prestígio associado ao resultado numérico representado pelo IDEB.
Denominações para o brinquedo “balanço” no estado de São Paulo: análise diatópica e léxico-semântica
Authors: Alencar Beatriz Aparecida
Published: July 2020

Considerando a relevância dos jogos e diversões infantis para a sociedade e a relação existente entre o modo de executar e de nomear próprio de cada grupo social, este estudo busca analisar as denominações do conceito expresso na pergunta 166/QSL do Projeto Atlas Linguístico do Brasil (ALiB): “como se chama uma tábua pendurada por meio de cordas, onde uma criança se senta e se move para frente e para trás?” (COMITÊ NACIONAL DO PROJETO ALIB, 2001, p. 35), examinando dados geolinguísticos de 47 localidades da rede de pontos do Projeto ALiB no estado de São Paulo (SP) e cidades limítrofes. O trabalho pautou-se em pressupostos teóricos da Dialetologia (CARDOSO, 2010), da Lexicologia (BIDERMAN, 1998), da Semântica (COSERIU, 1979) e da Etnolinguística (SAPIR, 1969), buscando demonstrar a inter-relação entre léxico, cultura e história social do estado de São Paulo.
QALY-Time: Experts’ View On The Use Of The Quality-Adjusted Life Year In Cost-Effectiveness Analysis In Palliative Care
Authors: Wichmann Anne B. , Goltstein Lia C.M.J. , Obihara Ndidi J. , Berendsen Madeleine R. , Houdenhoven Mark van , Morrison R. Sean , Johnston Bridget M. , Engels Yvonne
Published: July 2020

Background. The Quality-Adjusted Life Year (QALY) is internationally recognized as standard metric of health outcomes in cost-effectiveness analyses (CEAs) in healthcare. The ongoing debate concerning the appropriateness of its use for decision-making in palliative care has been recently mapped in a review. The aim was to report on and draw conclusions from two expert meetings that reflected on earlier mapped issues in order to reach consensus, and to advise on the QALY’s future use in palliative care. Methods. A nominal group approach was used. In order to facilitate group decision making, three statements regarding the use of the QALY in palliative care were discussed in a structured way. Two groups of international policymakers, healthcare professionals and researchers participated. Data were analysed qualitatively using inductive coding. Results. 1) Most experts agreed that the recommended measurement tool for the QALYs ‘Q’ component, the EuroQol-5D (EQ-5D), is inappropriate for palliative care. A more sensitive tool, which might be based on the capabilities approach, could be used or developed. 2) Valuation of time should be incorporated in the ‘Q’ part, leaving the linear clock time in the ‘LY’ component. 3) Most experts agreed that the QALY, in its current shape, is not suitable for palliative care. Conclusions. 1) Although the EQ-5D does not suffice, a generic tool is needed for the QALY. As long as no suitable alternative is available, other tools can be used besides or serve as basis for the EQ-5D because of issues in conceptual overlap. 2) Future research should further investigate the valuation of time issue, and how best to integrate it in the ‘Q’ component. 3) A generic outcome measure of effectiveness is essential to justly allocate healthcare resources. However, experts emphasized, the QALY is and should be one of multiple criteria for choices in the healthcare insurance package.
Drusen Characteristics of Type 2 Macular Neovascularization in Age-related Macular Degeneration
Authors: Ahmed Daniel , Stattin Martin , Haas Anna-Maria , Graf Alexandra , Krepler Katharina , Ansari-Shahrezaei Siamak
Published: July 2020

Background

To assess the relationship between drusen characteristics and type 2 macular neovascularization (MNV) in age-related macular degeneration (AMD)

Methods

Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging.

Results

Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 mm in 2 eyes (7.4%), drusen ≥ 63 mm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 mm in 2 eyes (8.7%), drusen ≥ 63 mm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 mm in affected eyes and 152 ± 41 mm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p=0.04) than patients without deposits (mean 77.40 ± 5.74).

Conclusions

Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.
Geographic Availability To Optometry Services Across Canada: Mapping Distribution, Need And Self-Reported Use
Authors: Shah Tayyab , Milosavljevic Stephan , Bath Brenna
Published: July 2020

Background: This research investigates the distribution of optometrists in Canada relative to population health needs and self-reported use of vision services.Methods: Optometrist locations were gathered from provincial regulatory bodies. Optometrist-to-population ratios (i.e. the number of providers per 10,000 people at the health region level) were then calculated. Utilization of vision care services was extracted from the Canadian Community Health Survey (CCHS) 2013-2014 question regarding self-reported contacts with optometrists or ophthalmologists. Data from the 2016 Statistics Canada census were used to create three population ‘need’ subgroups (65 years and over; low-income; and people aged 15 and over with less than a high school diploma). Cross-classification mapping compared optometrist distribution to self-reported use of vision care services in relation to need. Each variable was converted into three classes (i.e., low, moderate, and high) using a standard deviation (SD) classification scheme where ± 0.5SD from the mean was considered as a cut-off. Three classes: low (< -0.5SD), moderate (-0.5 to 0.5SD), and high ( > 0.5SD) were used for demonstrating distribution of each variable across health regions. Results: A total of 5,959 optometrists across ten Canadian provinces were included in this analysis. The nationwide distribution of optometrists is variable across Canada; they are predominantly concentrated in urban areas. The national mean ratio of optometrists was 1.70 optometrists per 10,000 people (range = 0.13 to 2.92). Out of 109 health regions (HRs), 26 were classified as low ratios, 51 HRs were classified as moderate ratios, and 32 HRs were high ratios. Thirty-five HRs were classified as low utilization, 39 HRs were classified as moderate, and 32 HRs as high utilization. HRs with a low optometrist ratio relative to eye care utilization and a high proportion of key sociodemographic characteristics (e.g. older age, low income) are located throughout Canada and identified with maps indicating areas of likely greater need for optometry services.Conclusion: This research provides a nationwide overview of vision care provided by optometrists identifying gaps in geographic availability relative to “supply” and “need” factors. This examination of variation in accessibility to optometric services will be useful to inform workforce planning and policies.
Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms
Authors: Tian Ning , Lv Dan-yu , Yu Ji , Ma Wan-yun
Published: July 2020

Background：Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.
Oxytocin Use in Trial of Labor after Cesarean and Its Relationship with Risk of Uterine Rupture in Women with One Previous Cesarean Section: A Meta-analysis of Observational Studies
Authors: ZHANG Huan , LIU Haiyan , LUO Shouling , Gu Weirong
Published: July 2020

Background Trial of labor after a previous cesarean delivery (TOLAC) has reduced the rate of cesarean sections. Nevertheless, the widespread use of TOLAC has been limited by an increase in adverse outcomes, the most serious one being the risk of symptomatic uterine rupture, which is possibly associated with oxytocin. In this meta-analysis, we explored the risk association between oxytocin use and uterine rupture in TOLAC. Methods Multiple electronic databases were searched for cross-sectional studies reporting on TOLAC, oxytocin and uterine rupture, which were published between January 1986 and October 2019. The bias-corrected Hedge's g was calculated as the effect size using the random-effects model. A two-sample Z test was used to compare the differences in synthetic rates. The Newcastle-Ottawa Scale was used to evaluate the risk of bias.Results A total of 14 studies, which included 48457 women who underwent TOLAC, met the inclusion criteria. The pooled rate of vaginal birth after a cesarean section (VBAC) and the rate of uterine rupture in spontaneous labor were 74.3% and 0.7%, respectively. In addition, the pooled rate of VBAC and the rate of uterine rupture in the induction labor group was 60.7% and 2.2%, respectively. The women who had spontaneous labor had a significantly higher rate of VBAC (p=0.0032) and a lower rate of uterine rupture (p=0.0003) compared to induced labor. The pooled rates of uterine rupture in women using oxytocin and women not using oxytocin in TOLAC were 1.4% and 0.5%, respectively, and the difference was significant (p=0.0002). Also, the synthetic rate of uterine rupture in oxytocin augmentation among women with spontaneous labor and women who had a successful induction of labor were 1.7% and 2.2%, respectively, without significant difference (p=0.443). Conclusions Women with induced labor had a higher risk of uterine rupture compared to women with spontaneous labor following TOLAC. Oxytocin use may increase this risk, which could be influenced by the process of induction or individual cervix condition. Consequently, simplified and standardized intrapartum management, precise protocol, and cautious monitoring of oxytocin use in TOLAC are necessary.
Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib
Authors: Bornemann Lea , Schuster Marc , Schmitz Saskia , Sobczak Charlyn , Bessen Clara , Merz Simon F. , Jöckel Karl-Heinz , Haverkamp Thomas , Gunzer Matthias , Göthert Joachim R.
Published: July 2020

Background The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML).Methods A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient’s neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2. Results Despite cytoreductive therapy with hydroxyurea, the patient’s WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within one week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted. Conclusion These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.
Symptoms of ocular surface disease in construction workers: comparative study with office workers.
Authors: Hernandez-Llamas Sergio , Paz-Ramos Ana Karen , Marcos-González Patricio , Amparo Francisco , Garza-Leon Manuel
Published: July 2020

Background: To investigate and contrast the prevalence of dry eye symptoms in construction workers and office workers using the OSDI questionnaire.Methods: A cross-sectional, observational study was conducted using the OSDI questionnaire to evaluate dry eye symptoms and associated risk factors. Sampled size calculation with a power of 80% and a 95% degree of confidence suggested the inclusion of 298 participants. Results: We studied 304 subjects (149 construction workers and 155 office workers). More than half (55%) of the participants presented dry eye symptoms (OSDI > 12). The average OSDI score was 21.30 ± 22.20 points, being lower in the group of construction workers (12.45±17.50) than in-office workers (28.51±22.99) (p <0.001). Considering participants who had moderate and severe symptoms (23 to 100 points in OSDI), office workers presented dry eye symptoms 4.15 times more frequently than construction workers (OR 4.15, 95% CI 2.52, 6.85). Women presented statistical evidence of higher OSDI scores than men (32.47 ± 23.72 vs. 14.87 ± 18.48, respectively). Conclusions: construction workers have four times less risk of presenting dry eye symptoms than people working in the average office space. This highlights the pernicious effects on the ocular surface of the office environment, which poses a significant risk for the development or worsening of dry eye symptoms.
The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma
Authors: Wang Jie , Tian Shu , Sun Ji , Zhang Jiahao , Lin Lan , hu chunyan
Published: July 2020

Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.
A new view into the silica deposition vesicles of diatoms
Authors: Heintze Christoph , Formanek Petr , Pohl Darius , Hauptstein Jannes , Rellinghaus Bernd , Kröger Nils
Published: July 2020

Diatoms are single-celled microalgae that produce silica-based cell walls with intricate nano- and micropatterns. Biogenesis of diatom biosilica is a bottom-up process that occurs in large intracellular compartments termed silica deposition vesicles (SDVs). Investigating the mechanism of silica morphogenesis has so far been severely limited by the lack of methods for imaging the entire volume of an SDV with high spatial resolution during all stages of development. Here we have developed a method that allows for rapid identification and electron microscopy imaging of many different, full sized SDVs that are in the process of producing biosilica valves. This enabled visualizing the development of characteristic morphological biosilica features with unprecedented spatio-temporal resolution. During early to mid-term development, valve SDVs contained ~20 nm sized particles that were primarily associated with the radially expanding rib-like biosilica structures. The results from electron dispersive X-ray analysis suggests that the immature biosilica patterns are silica-organic composites. This supports the hypothesis that silica morphogenesis is dependent on organic biomolecules inside the SDV lumen.
Consolidating strategic information to monitor progress against the UNAIDS 90-90-90 targets: evaluating the operational feasibility of an electronic HIV testing register in Cape Town, South Africa
Authors: Jacob Nisha , Rice Brian , Kalk Emma , Heekes Alexa , Morgan Jennie , Brinkmann Samantha , Hargreaves James , Orgill Marsha , Boulle Andrew
Published: July 2020

Background HIV diagnosis in South Africa is based on a point-of-care testing (PoCT) algorithm with paper-based record-keeping. Aggregated testing data are reported routinely. To facilitate improved HIV case-based surveillance, the Western Cape Province implemented a unique pilot intervention to digitise PoCT results, at an individual level, and generate an electronic register using the newly developed Provincial Health Data Centre (PHDC). We describe the intervention (phased) and present an evaluation of the operational feasibility of the intervention. We also offer implementation insights into establishing electronic capture of individual level testing data. Cross-sectional analyses were conducted on records of all patients attending a local Community Health Centre who had an HIV-PoCT during the study period. Data from the intervention were linked to the PHDC using a unique identifier and compared with aggregate data from the paper-based register. Correlation coefficients were calculated to quantify the correlation between the two monthly datasets. To support an understanding of the findings, the Department of Health project management team generated reflections on the implementation process, which were then grouped thematically into implementation lessons. Results In total, 11 337 PoCT records were digitised (70% (7954) during Phase I; and 30% (3383) during Phase II). Linkage of forms to the PHDC was 96% in Phase I and 98% in Phase II. Comparison with aggregate data showed high correlation during Phase I, but notable divergence during Phase II. Divergence in Phase II was due to stringent data quality requirements and high clinical staff turnover. Factors supporting implementation success in Phase I included direct oversight of data capturing by a manager with clinical and operational insight. Implementation challenges included operational, health system, and high cost-related issues. Conclusions We demonstrate that rapid digitisation of HIV PoCT data, without compromising currently collected aggregate data, is operationally feasible, and can contribute to person-level longitudinal HIV case-based surveillance. To take to scale, we will need to improve PoCT platforms and clerical and administrative systems. Although we highlight challenges, we demonstrate that electronic HIV testing registers can successfully replace manual registers and improve efforts to monitor and evaluate HIV testing strategies.
Mitochondrial accumulation of Apurinic/Apyrimidinic Endonuclease 1 protein in early stages of hepatocellular carcinoma enhances mtDNA repair rate, contributing to cell proliferation and mitochondrial functionality.
Authors: Bazzani Veronica , Barchiesi Arianna , Radecka Dorota , Pravisani Riccardo , Guadagno Antonio , Loreto Carla Di , Baccarani Umberto , Vascotto Carlo
Published: July 2020

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC.Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration.Results: APE1’s cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1’s mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix.Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA.
pH Sensitive Lipid-Polymer Hybrid Nanoparticles Mediated Delivery of Docetaxel: A Viable Approach for Breast Cancer Therapeutic Intervention Development
Authors: Yuan Ye , Song Jia-Xing , Zhang Mei-Na , Yuan Baoshan
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
Identification of Prognosis-Related Genes and Construction of Multi-regulatory Networks in Pancreatic Cancer Microenvironment by Bioinformatics Analysis
Authors: Li Tong , Liu Qiaofei , Zhang Ronghua , Liao Quan , Zhao Yupei
Published: July 2020

Background: As one of the most lethal cancers, pancreatic cancer has been characterized by abundant supportive tumor-stromal cell microenvironment. Although the advent of tumor-targeted immune checkpoint blockers has brought light to patients with other cancers, its clinical efficacy in pancreatic cancer has been greatly limited due to the protective stroma . Thus, it is urgent to find potential new targets and establish multi-regulatory networks to predict patient prognosis andimprove treatment. Methods: We followed a strategy based on mining the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm to obtain the immune scores and stromal scores. Differentially expressed genes (DEGs) associated with poor overall survival of pancreatic cancer were screened from a TCGA cohort. By comparing global gene expression with high vs. low immune scores and subsequent Kaplan-Meier analysis, DEGs that significantly correlate with poor overall survival of pancreatic cancer in TCGA cohort were extracted. After constructing the protein-protein interaction network using STRING and limiting the genes within the above DEGs, we utilized RAID 2.0, TRRUST v2 database and degree and betweenness analysis to obtain non-coding RNA (ncRNA)-pivotal nodes and TF-pivotal nodes. Finally, multi-regulatory networks have been constructed and pivotal drugs with potential benefit for pancreatic cancer patients were obtained by screening in the DrugBank. Results: In this study, we obtained 246 DEGs that significantly correlate with poor overall survival of pancreatic cancer in the TCGA cohort. With the advent of 38 ncRNA-pivotal nodes and 7 TF-pivotal nodes, the multi-factor regulatory networks were constructed based on the above pivotal nodes. Prognosis-related genes and factors such as HCAR3, PPY, RFWD2, WSPAR and Amcinonide were screened and investigated. Conclusion: The multi-regulatory networks constructed in this study are not only beneficial to improve treatment and evaluate patient prognosis with pancreatic cancer, but also favorable for implementing early diagnosis and personalized treatment. It is suggested that these factors may play an essential role in the progression of pancreatic cancer.