bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Catenin Attenuation Inhibits Tumor Growth and Promotes Differentiation in a BRAFV600E-Driven Thyroid Cancer Animal Model
Authors: Zou Minjing , BinEssa Huda A. , Al-Malki Yousif H. , Al-Yahya Suhad , Al-Alwan Monther , Al-Jammaz Ibrahim , Khabar Khalid S.A. , Almohanna Falah , Assiri Abdullah M. , Meyer Brian F. , Alzahrani Ali S. , Al-Mohanna Futwan A. , Shi Yufei
Published: June 2021

BRAFV600E mutation is the most frequent genetic alteration in papillary thyroid cancer (PTC). β-Catenin (Ctnnb1) is a key downstream component of canonical Wnt signaling pathway and is frequently overexpressed in PTC. BRAFV600E-driven tumors have been speculated to rely on Wnt/β-catenin signaling to sustain its growth, although many details remain to be elucidated. In this study, we investigated the role of β-catenin in BrafV600E-driven thyroid cancer in a transgenic mouse model. In BrafV600E mice with wild-type (WT) Ctnnb1 (BVE-Ctnnb1WT or BVE), overexpression of β-catenin was observed in thyroid tumors. In BrafV600E mice with Ctnnb1 knockout (BVE-Ctnnb1null), thyroid tumor growth was slowed with significant reduction in papillary architecture. This was associated with increased expression of genes involved in thyroid hormone synthesis, elevated 124iodine uptake, and serum T4. The survival of BVE-Ctnnb1null mice was increased by more than 50% during 14-month observation. Mechanistically, downregulation of MAPK, PI3K/Akt, and TGFβ pathways and loss of epithelial–mesenchymal transition (EMT) were demonstrated in the BVE-Ctnnb1null tumors. Treatment with dual β-catenin/KDM4A inhibitor PKF118–310 dramatically improved the sensitivity of BVE-Ctnnb1WT tumor cells to BRAFV600E inhibitor PLX4720, resulting in significant growth arrest and apoptosis in vitro, and tumor regression and differentiation in vivo. These findings indicate that β-catenin signaling plays an important role in thyroid cancer growth and resistance to BRAFV600E inhibitors. Simultaneously targeting both Wnt/β-catenin and MAPK signaling pathways may achieve better therapeutic outcome in BRAFV600E inhibitor-resistant and/or radioiodine-refractory thyroid cancer.
Influence of Changes in Obesity Indicators on the Risk of Hypertension: A Cohort Study in Southern China
Authors: Peng Xin , Huang JunXuan , Liu Yan , Cheng MengJiao , Li Bo , Li RuiLing , Wang PeiXi
Published: June 2021

Objectives: The objective of this study was to demonstrate the association between changes in different obesity indicators and the risk of incident hypertension by the age-group among community-dwelling residents in southern China. Methods: A total of 6,959 non-hypertensive participants aged ≥18 years old were enrolled in this cohort study and completed questionnaire interviews and anthropometric measurements at baseline (2010) and follow-up (2017). A time-dependent covariate Cox proportional hazard model considered the changes in obesity indicators during the follow-up period and calculated the hazard ratios (HRs) to analyze the risk of incident hypertension according to different obesity indicators. Results: During a mean follow-up of 7.1 years, 1,904 participants were newly diagnosed with hypertension. The body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were significantly positively associated with an increased future risk of incident hypertension, and BMI was the best predictive indicator of hypertension (obesity in men: HR = 2.65, 95% confidence interval (CI) = 2.20–3.20; obesity in women: HR = 2.80, 95% CI = 2.27–3.45). Compared with the middle-aged and older group, the risk of incident hypertension was highest in the younger group which had the highest baseline obesity indicators. Conclusions: Changes in obesity indicators were significantly associated with the risk of incident hypertension in all age-groups, and the risk of future incident hypertension increased with the increase in baseline obesity indicators.
Brain Infarction MRI Pattern in Stroke Patients with Intracardiac Thrombus
Authors: Trandafir Cassiana , Sandiramourty Shridevi , Laurent-Chabalier Sabine , Ter Schiphorst Adrien , Nguyen Hai , Wacongne Anne , Ricci Jean-Etienne , Pereira Fabricio , Thouvenot Eric , Renard Dimitri
Published: June 2021

Background: Acute infarction patterns have been described in cardioembolic stroke, mainly with atrial fibrillation (AF) or patent foramen ovale. We aimed to analyse acute infarction magnetic resonance imaging (MRI) characteristics in stroke patients with intracardiac thrombus (ICT) compared with stroke patients with AF. Methods: We performed a retrospective study analysing brain MRI scans of consecutive acute symptomatic cardioembolic infarction patients associated with ICT or AF who were recruited and registered in the stroke database between June 2018 and November 2019. Diffusion-weighted imaging performed within 1 week after symptom onset, intra-/extracranial vessel imaging, echocardiography, and ≥24-h ECG monitoring were required for inclusion. Baseline, biological, and echocardiography characteristics were assessed. Analysed MRI characteristics were infarction location (anterior/middle/posterior cerebral artery territory; anterior/posterior/mixed anterior-posterior circulation; multiterritorial infarction; brainstem; cerebellum; small cortical cerebellar infarctions [SCCIs] or non-SCCI; cortical/subcortical/cortico-subcortical), lesion number, subcortical lesion size (> or <15 mm), and total infarction volume. Results: We included 28 ICT and 94 AF patients presenting with acute stroke. ICT patients were younger (median age 66 vs. 81 years, p < 0.001), more frequently male (79 vs. 47%, p = 0.003), and smokers (39 vs. 17%, p = 0.013), had more frequent history of diabetes (36 vs. 18%, p = 0.049) and ischaemic heart disease (57 vs. 21%, p < 0.001), and had lower HDL cholesterol levels (0.39 vs. 0.53 g/L, p < 0.001). On MRI, SCCI was more frequent in the ICT group (25 vs. 5%, p = 0.006) in the absence of other differences in infarction localisation, number, size, or volume on MRI. On multivariate analysis, younger age (p < 0.001), history of ischaemic heart disease (p < 0.001), and low HDL cholesterol levels (p = 0.01) were significantly associated with ICT. Results approaching statistical significance were observed for SCCI (more frequent in the ICT group, p = 0.053) and non-SCCI (more frequent in the AF group, p = 0.053) on MRI. Conclusions: ICT-related stroke is associated with acute SCCI presence on MRI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT04456309.
Pseudoprogression with Neoadjuvant Immunotherapy for Cutaneous Melanoma
Authors: Garcia Diogo , Beal Juliana Rodrigues , Alvarez Daniel Mamere , Macarenco Ricardo Silvestre e Silva , Schvartsman Gustavo
Published: June 2021

Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5–10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2–3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.
Successful Treatment with Intravenous and Intravascular Cidofovir for BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report
Authors: Mehrvar Azim , Naderi Ali , Mehrvar Narjes , Nourian Mahyar
Published: June 2021

BK virus rarely causes disease but is typically associated with patients who have had a transplant. The cornerstone of therapy is reduction in immunosuppression. A recent surge in BKVAN correlates with use of potent immunosuppressant drugs, such as tacrolimus and mycophenolate mofetil. Studies have not shown any correlation between BKVAN and a single immunosuppressive agent but rather the overall immunosuppressive load. A 12-year-old male with recurrent acute myeloblastic leukemia (M4) was undergoing chemotherapy regimen at MAHAK Pediatric Cancer Treatment and Research Center. Following 28 days of allogenic transplantation with protocol BU/CY/Mel from his brother, he had severe hematuria in urine. So he was screened for the reason of hematuria. The results of screening showed that he had positive BK virus in urine (viral load PCR tests: 7128037228 IU/ML). According to grade IV hemorrhagic cystic, cidofovir was administered for the first time as IV and then 2 times as intravesical. After the administration of cidofovir, the symptoms of hematuria improved and the load of BK virus decreased that finally accounted as zero. Cidofovir could be the target issue in patients’ recovery. Authors suggest further evaluations of cidofovir both in allogeneic stem cell transplantation setting and in renal allograft patients to consider its impact on BKV and nephropathy.
High Tissue TLR5 Expression Predicts Better Outcomes in Colorectal Cancer Patients
Authors: Beilmann-Lehtonen Ines , Hagström Jaana , Mustonen Harri , Koskensalo Selja , Haglund Caj , Böckelman Camilla
Published: June 2021

Background: Colorectal cancer (CRC), the third most common cancer globally, caused 881,000 cancer deaths in 2018. Toll-like receptors (TLRs), the primary sensors of pathogen-associated molecular patterns and damage-associated molecular patterns, activate innate and adaptive immune systems and participate in the development of an inflammatory tumor microenvironment. We aimed to explore the prognostic value of TLR3, TLR5, TLR7, and TLR9 tissue expressions in CRC patients. Methods: Using immunohistochemistry, we analyzed tissue microarray samples from 825 CRC patients who underwent surgery between 1982 and 2002 at the Department of Surgery, Helsinki University Hospital, Finland. After analyzing a pilot series of 205 tissue samples, we included only TLR5 and TLR7 in the remainder of the patient series. We evaluated the associations between TLR5 and TLR7 tissue expressions, clinicopathologic variables, and survival. Using the Kaplan-Meier method, we generated survival curves, determining significance using the log-rank test. Univariate and multivariate survival analyses relied on the Cox proportional hazards model. Results: The 5-year disease-specific survival was 55.9% among TLR5-negative (95% confidence interval [CI] 50.6–61.2%) and 61.9% (95% CI 56.6–67.2%; p = 0.011, log-rank test) among TLR5-positive patients. In the Cox multivariate survival analysis adjusted for age, sex, stage, location, and grade, positive TLR5 immunoexpression (hazard ratio [HR] 0.74; 95% CI 0.59–0.92; p = 0.007) served as an independent positive prognostic factor. TLR7 immunoexpression exhibited no prognostic value in the survival analysis across the entire cohort (HR 0.97; 95% CI 0.78–1.20; p = 0.754) nor in subgroup analyses. Conclusions: We show for the first time that a high TLR5 tumor tissue expression associates with a better prognosis in CRC patients.
Association of Immunosuppressants with Mortality of Patients with Bullous Pemphigoid: A Nationwide Population-Based Cohort Study
Authors: Wu Chen-Yi , Wu Chun-Ying , Li Chung-Pin , Lin Yi-Hsian , Chang Yun-Ting
Published: June 2021

Background: Bullous pemphigoid (BP) is a common autoimmune blistering skin disease with substantial mortality. Objective: To identify whether the use of immunosuppressants was associated with reduced mortality in BP patients. Methods: The data for this study were obtained from the National Health Insurance Research Database in Taiwan from January 1, 1997 to December 31, 2013. Those BP patients receiving any immunosuppressant for ≥28 days per month for 3 consecutive months were defined as the immunosuppressant cohort. In total, 452 BP patients on immunosuppressants were matched 1:4 by age, sex, propensity score of comorbidities, and use of tetracycline with 1,808 BP patients taking only corticosteroids. Results: The immunosuppressant cohort had a significantly lower 5-year mortality rate than the corticosteroid cohort (0.57 vs. 0.67). In the multivariable regression analysis adjusted for covariates, the use of immunosuppressants significantly reduced the risk of mortality (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.68–0.90, p < 0.001). Hyperlipidemia also reduced risk of mortality. However, age, diabetes, renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, and dementia were significant risk factors for mortality. In the subgroup analysis, the risk of mortality decreased most substantially in those aged <70 years (HR: 0.45, 95% CI: 0.28–0.72). Conclusion: Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged <70 years, with a 55% reduced risk of mortality.
Transcutaneous versus Total Serum Bilirubin Measurements in Preterm Infants
Authors: Jegathesan Thivia , Campbell Douglas M. , Ray Joel G. , Shah Vibhuti , Berger Howard , Hayeems Robin Z. , Sgro Michael ,   for the NeoHBC
Published: June 2021

Introduction: Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. Methods: A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. Results: The overall mean TcB-TSB difference was −24.5 μmol/L (95% LOA −103.3 to 54.3), 1.6 μmol/L (95% LOA −73.4 to 76.5) before phototherapy, and −31.1 μmol/L (95% LOA −105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was −15.2 μmol/L (95% LOA −86.8 to 56.3) at the forehead and −24.4 μmol/L (95% LOA −112.9 to 64.0) at the sternum. The mean TcB-TSB difference was −31.4 μmol/L (95% LOA −95.3 to 32.4) among infants born 24–28 weeks, −25.5 μmol/L (95% LOA −102.7 to 51.8) at 29–32 weeks, and −15.9 μmol/L (95% LOA −107.4 to 75.6) at 33–35 weeks. Measures did not differ by maternal ethnicity. Conclusion: Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at <33 weeks’ gestation, as TcB approaches treatment thresholds. Its underestimation of TSB after the initiation of phototherapy warrants the use of TSB for clinical decision-making after the initiation of phototherapy.
Dendritic Integration Dysfunction in Neurodevelopmental Disorders
Authors: Nelson Andrew D. , Bender Kevin J.
Published: June 2021

Neurodevelopmental disorders (NDDs) that affect cognition, social interaction, and learning, including autism spectrum disorder (ASD) and intellectual disability (ID), have a strong genetic component. Our current understanding of risk genes highlights two main groups of dysfunction: those in genes that act as chromatin modifiers and those in genes that encode for proteins localized at or near synapses. Understanding how dysfunction in these genes contributes to phenotypes observed in ASD and ID remains a major question in neuroscience. In this review, we highlight emerging evidence suggesting that dysfunction in dendrites – regions of neurons that receive synaptic input – may be key to understanding features of neuronal processing affected in these disorders. Dendritic integration plays a fundamental role in sensory processing, cognition, and conscious perception, processes hypothesized to be impaired in NDDs. Many high-confidence ASD genes function within dendrites where they control synaptic integration and dendritic excitability. Further, increasing evidence demonstrates that several ASD/ID genes, including chromatin modifiers and transcription factors, regulate the expression or scaffolding of dendritic ion channels, receptors, and synaptic proteins. Therefore, we discuss how dysfunction of subsets of NDD-associated genes in dendrites leads to defects in dendritic integration and excitability and may be one core phenotype in ASD and ID.
Extracellular Uridine Nucleotides-Induced Contractions Were Increased in Femoral Arteries of Spontaneously Hypertensive Rats
Authors: Matsumoto Takayuki , Takayanagi Keisuke , Katome Tomoki , Kojima Mihoka , Taguchi Kumiko , Kobayashi Tsuneo
Published: June 2021

Introduction: Femoral arterial dysfunction including abnormal vascular responsiveness to endogenous ligands was often seen in arterial hypertension. Extracellular nucleotides including uridine 5′-diphosphate (UDP) and uridine 5′-triphosphate (UTP) play important roles for homeostasis in the vascular system including controlling the vascular tone. However, responsiveness to UDP and UTP in femoral arteries under arterial hypertension remains unclear. The aim of this study was to investigate if hypertension has an effect of vasoconstrictive responsiveness to UDP and UTP in femoral arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) after 7 and 12 months old. Methods: Organ baths were conducted to determine vascular reactivity in isolated femoral arterial rings. Results: In femoral arteries obtained from 12-month-old rats, augmented contractile responses to UDP and UTP were seen in femoral arteries of SHR than in those of WKY under situations not only intact but also nitric oxide synthase inhibition, whereas no difference of extracellular potassium-induced vasocontraction was seen in both SHR and WKY groups. Similar contraction trends occurred in femoral arteries obtained from 7-month-old rats. Moreover, contractions induced by UDP and UTP were increased in endothelium-denuded arteries. Cyclooxygenase inhibition decreased the contractions induced by these nucleotides and abolished the differences in responses between the SHR and WKY groups. Conclusions: This study demonstrates the importance of regulation of extracellular uridine nucleotides-induced contractions in hypertension-associated peripheral arterial diseases.
Reajuste de preços na indústria farmacêutica brasileira e o fator X: uma avaliação usando o método de fronteiras estocásticas
Authors: Rocha Fabiana , Souza Igor Viveiros
Published: June 2021

O objetivo deste artigo é propor uma metodologia alternativa aquela apresentada pela resolução da CMED para calcular a produtividade da indústria farmacêutica durante o período 2000-2006. Utiliza-se o índice de produtividade total dos fatores (PTF) de Malmquist proposto por Caves, Christensen e Diwert (1982). Para a obtenção do índice é aplicada a metodologia de fronteiras estocásticas desenvolvida por Battese e Coelli (1995). Esta metodologia permite a separação da PTF em variação na eficiência técnica (uso da melhor tecnologia disponível) e variação tecnológica (mudanças na fronteira de produção propriamente dita). Utiliza-se uma base de dados única obtida através de pesquisa feita pela FIPE junto a empresas da indústria farmacêutica. Os resultados indicam uma perda de produtividade em 2005 e 2006, ao contrário do que estabelece o governo.
Um modelo para a criminalidade no município de São Paulo em 2001
Authors: Sartoris Alexandre
Published: June 2021

Este trabalho tem como objetivo estimar um modelo empírico para três tipos de crime no município de São Paulo: homicídios, roubos e furto de veículos. O trabalho usa como unidades geográficas as áreas de atuação dos distritos policiais e leva em conta possíveis efeitos espaciais entre as variáveis. Os resultados mostram diferenças importantes quando tratamos com crimes contra a pessoa e contra a propriedade.
Caracterização da trajetória tecnológica da biotecnologia agrícola por meio de redes de patentes
Authors: Da Silveira José Maria Ferreira Jardim , Dal Poz Maria Ester , Massago Fabio Kenji , Campos Rafael
Published: June 2021

O trabalho apresenta a trajetória tecnológica de plantas transgênicas e seus principais atores. Resulta da aplicação de uma metodologia de análise de patentes em redes de co-citação desenvolvida pelos autores e baseada no trabalho de Verspangen (2007). Tomando em consideração o conhecimento acumulado em mais de dez anos de desenvolvimento da biotecnologia agrícola, o trabalho apresenta evidências para a melhor compreensão para o sucesso das plantas transgênicas apesar das barreiras impostas em alguns países desenvolvidos à sua difusão. Biotecnologia e o bionegócio são claramente definidos como atividades baseadas em ciência (Bell e Pavitt 1993). Todavia há um debate se a biotecnologia constitui-se em um novo setor econômico ou se é apenas um conjunto de tecnologias que fazem parte de outras trajetórias tecnológicas tradicionais, particularmente do setor farmacêutico. Silveira, Futino e Olalde (2002) trazem evidências ao fato de que o desenvolvimento da biotecnologia, desde o início dos anos 90, fornece a resposta ao baixo dinamismo de muitas indústrias das áreas de saúde humana, meio ambiente e agricultura. Walsh (1993) evidencia o papel da biotecnologia em criar novas demandas e um novo aparato regulatório (veja Aoki 2007). Por outro lado, a persistência da biotecnologia tradicional e intermediária, combinada ou não com inovações biotecnológicas jogaria dúvidas sobre a pertinência do conceito de trajetória tecnológica aplicada à biotecnologia (Russel 1999). O trabalho lança evidências à ideia de que a biotecnologia e a biologia molecular são os fundamentos do bionegócio inovativo. Além disto, mostra a importância do comportamento estratégico em nível de descoberta de genes como um guia para a criação de empresas biotecnológicas competitivas.
Estimativa da economia governamental advinda do emprego do fator previdenciário
Authors: Superti Luiz Henrique Ferreira Cruz e , Wu Helen , Cruz Paloma Soares Novello
Published: June 2021

O presente trabalho tem como escopo estimar a economia proporcionada pelo emprego do fator previdenciário, introduzido pela Lei 9.876/99. Este tema ganhou notoriedade devido às discussões referentes à extinção do fator no primeiro semestre de 2010, questão originada do Projeto de Lei 3.299/08. A partir de informações do Instituto Brasileiro de Geografia e Estatística (IBGE) e de cruzamentos de dados obtidos do Anuário Estatístico da Previdência Social InfoLogo (AEPS InfoLogo), foi desenvolvido um exercício empírico contrafactual. Este possibilitou o cálculo da economia obtida pelo governo para as Aposentadorias por Tempo de Contribuição (ATC) concedidas de 2000 até 2009, desde o seu deferimento até a morte de todos os requerentes do período analisado. Verifica-se, como resultado, que o governo gastaria a mais cerca de R$10 bilhões anuais e que a aplicação do fator resultou em economia de mais de 30% dos gastos totais com as ATCs desse período. A principal conclusão do estudo é que, se o fator previdenciário fosse extinto, o governo teria um dispêndio maior, que possivelmente seria intensificado pelo envelhecimento demográfico brasileiro. Desta forma, percebe-se a relevância do mecanismo para a manutenção do sistema previdenciário do país.
A influência dos ativos intangíveis na criação de valor de empresas norte-americanas do setor de serviços ao consumidor
Authors: Braune Erica Sumoyama , Saliba Juliana Albuquerque , Basso Leonardo Fernando Cruz , Kimura Herbert
Published: June 2021

As empresas estão focando nos ativos intangíveis com a intenção de obter vantagem competitiva, no entanto, não há uma forma sistemática de calculá-los. Gu e Lev (2003) propõem um modelo de mensuração dos ativos intangíveis, onde o desempenho econômico da empresa é gerado por ativos físicos, financeiros e intangíveis. Baseado nessa proposta, calculamos o intangible capital (IC), o intangibles-drive-earnings (IDE) e os índices de desempenho para empresas do setor de serviços ao consumidor dos Estados Unidos de acordo com a disponibilidade de dados no período de 1998 a 2010. Utilizamos o modelo de dados em painel, para analisarmos simultaneamente as empresas e suas variáveis ao longo do tempo. Os resultados mostram que o comprehensive value tem uma relação positiva e significante com o Valor de Mercado e que o IC e do IDE possuem uma relação positiva e significante com as variáveis de pesquisa e desenvolvimento e dispêndio de capital, variáveis de demonstrações financeiras que são comumente usadas como proxies para os intangíveis. A pesquisa pode ser ampliada para empresas publicas onde seja possível a obtenção de variáveis oriundas de balanços e para as quais seja possível calcular o valor de mercado. Empresas públicas não podem mais ser tratadas como entidades diferenciadas de empresas privadas no que concerne a avaliação de desempenho, pois a ineficiência pública vai implicar perda de eficiência para as empresas privadas. Assim modelos como os que testamos aqui poderiam ser testados no setor público para verificar se resultados semelhantes são obtidos.
O desenvolvimento do setor artesanal paulista: uma análise crítica da sua qualificação gerencial
Authors: Hemzo Miguel Angelo , Andrade Josmar , Dos Santos Roberto Mauro
Published: June 2021

Segundo o Ministério do Desenvolvimento da Indústria e Comércio a atividade artesanal representa 2,8% do PIB nacional, envolvendo 8,5 milhões de pessoas. Além de sua importância econômica, este tipo de atividade também fortalece a identidade nacional e tem grandes impactos culturais. Contudo é pouco estudada pelo ponto de vista gerencial, merecendo maior atenção pela sua importância estratégica. Este artigo tem o intuito de analisar, crítica e negocialmente, a condição do setor. Por meio de estudo exploratório que observou as características e atividades de 61 grupos de artesãos de várias regiões de São Paulo, os resultados indicam a necessidade de maior conhecimento gerencial por parte dos artesãos de forma a aumentar sua autonomia e visão sistêmica do processo, sem depender continuamente de posturas paternalistas e assistencialistas de agências governamentais e organizações de terceiro setor. Isso seria muito importante para alavancar o potencial inclusivo e sustentável desta atividade, especialmente junto a setores mais pobres da sociedade, sendo importante, ao mesmo tempo, estabelecer condições para preservação do valor cultural deste tipo de produção.
Eficácia na contratualização intergovernamental na Austrália
Authors: Levy Evelyn
Published: June 2021

Esse artigo traz os resultados da pesquisa documental e das entrevistas feitas sobre os arranjos institucionais usados pelo governo australiano para facilitar a coordenação de atividades governamentais no governo federal da Austrália (Commonwealth) e os estados e territórios. O artigo conclui apresentando algumas considerações sobre a eficácia que o sistema tem demonstrado, assim como alguns de seus entraves e discute a possibilidade da adoção de algumas de suas inovações no federalismo brasileiro.
Democratização na construção de políticas públicas: Conferências municipais populares nos processos de formulação
Authors: Crantschaninov Tamara Ilinsky , De Medeiros Anny Karine
Published: June 2021

O presente artigo visa relatar, a partir de experiências empíricas, como instrumentos institucionais de participação influenciam e modificam a construção de políticas públicas. A abertura democrática no Brasil deu-se de forma institucional, sendo ainda necessário verificar como se dão os processos de interação entre governo e sociedade civil, bem com o peso de cada uma no processo de decisão sobre políticas públicas. As conferências são uma das maneiras de analisar como se desdobra esta possibilidade no contexto brasileiro. Dessa forma, será analisada a participação da sociedade civil no processo de formulação de políticas públicas, tendo como método o estudo e comparação de dois casos ocorridos em 2011, a IX Conferência Municipal de Assistência Social da Cidade de São Paulo e o III Plano Municipal de Segurança Pública de Diadema. Ambos os casos demonstram a fragilidade do processo de participação em dar voz a todos os participantes de forma equilibrada, e em garantir que as propostas sejam efetivamente assumidas na agenda governamental, mas igualmente demonstram um processo de amadurecimento e aprendizado, no qual a sociedade começa a tomar consciência de seu papel cidadão através do próprio processo participativo.
Caso para ensino: Base comunitária de segurança da Vila Formosa, São Paulo (SP)
Authors: Martinelli Bruno , Marconato Caio Siqueira , Amado Kayo Felype Nachtajler
Published: June 2021

Um caso para ensino é um relato de situações da vida organizacional, com o objetivo de desenvolver habilidades de resolução de problemas. Este estudo de caso para ensino é contado sob a ótica do Sargento Ciriaco, comandante da base. Desde 2007, a Base da Polícia Militar de Vila Formosa, localizada na zona leste do município de São Paulo, faz parte do programa de policiamento comunitário. Em agosto de 2008, no início da gestão do Sargento Ciriaco, foi adotada a filosofia da integração com a comunidade. Parcerias com a polícia comunitária do Japão, comerciantes locais, e outros órgãos do governo foram realizadas com objetivo de viabilizar recursos financeiros, físicos e humanos para os projetos. Apesar dos recursos escassos e poucos incentivos à inovação, o Sargento Ciriaco e seus comandados se superaram para proporcionar resultados de integração e segurança no bairro de Vila Formosa, através de diversos projetos e ações apresentados neste trabalho. A base apresenta-se como um case de sucesso dentro da corporação, que além de atingir a integração proposta, interagiu com muita dinâmica e criatividade com a sociedade. Os resultados obtidos apresentam-se através da redução do número de delitos na região e da constatação de um sentimento diferente da população acerca do papel da polícia como um parceiro da comunidade. Após a apresentação do caso, seguem notas de ensino para aplicação do caso em sala de aula. A experiência relatada foi uma das premiadas na categoria inovação pela 7ª edição do Prêmio Mário Covas (2010-2011), realizado pela Secretaria Estadual de Gestão Públicas em parceria com a Fundação do Desenvolvimento Administrativo (FUNDAP) e a Fundação Mário Covas. O objetivo do prêmio é reconhecer e premiar iniciativas de excelência ou inovação no setor público estadual paulista em diversas categorias.
Aplicação do modelo multidimensional-reflexivo para análise de uma entidade pública municipal: Autarquia de Esporte e Lazer do Recife (PE)
Authors: Almeida Brunna Carvalho , Paula Sílvio Luiz de
Published: June 2021

Este artigo tem como objetivo proceder a análise organizacional-administrativa de uma entidade pública que não tem como fim a maximização de lucro. A organização estudada tem por missão de desenvolver o esporte e lazer popular, no município do Recife. No decorrer deste trabalho serão apresentadas as características estruturais e dos agentes do Ginásio de Esportes Geraldo Magalhães com base no modelo multidimensional-reflexivo, que originalmente foi concebido para analisar entidades privadas. Para tanto, os procedimentos analíticos foram pautados nas técnicas de pesquisa documental e bibliográfica, assim como a abordagem através do “sujeito implicado” e do “artesanato intelectual”, em conformidade com um critério da investigação do conteúdo, o que caracteriza essa pesquisa como exploratório-descritiva. O resultado indica a possibilidade da classificação da autarquia pesquisada (tipo real) próxima ao tipo ideal proposta pelo modelo multidimensional reflexivo. Essa classificação representa um construto que possibilita a análise de uma organização pública, neste caso, a Autarquia de Esporte e Lazer do Recife, que apresentou uma significativa aproximação com uma variante do tipo-base equiparativo-adaptador.
Association of Differential Leukocyte Count With Incident Abdominal Aortic Aneurysm Over 22.5 Years: The ARIC Study
Authors: Parikh Romil R. , Folsom Aaron R. , Poudel Kripa , Lutsey Pamela L. , Demmer Ryan T. , Pankow James S. , Chen Lin Y. , Tang Weihong
Published: June 2021

Objective:

Leukocytes contribute to the development of abdominal aortic aneurysm (AAA). We evaluated whether associations of differential leukocyte counts with AAA persist after accounting for traditional risk factors of AAA.

Approach and Results:

Among 11 217 adults from the Atherosclerosis Risk in Communities Study, we evaluated associations of differential leukocyte counts at baseline (1987–1989) with incident AAAs over a median follow-up of 22.5 years, using Cox proportional hazards regression. Each differential leukocyte count was categorized into 5 groups—below normal, tertiles within the normal range, and above normal, with the first tertile serving as the referent. We identified 377 incident AAAs through 2011, using hospital discharge diagnoses, linked Medicare records, or death certificates. At baseline, higher neutrophil, monocyte, and eosinophil counts were associated with higher risk of AAA, independent of smoking, other differential leukocyte counts, and other traditional risk factors. The association with incident AAA was the strongest for above normal neutrophil count, with an adjusted hazard ratio (95% CI) of 2.17 (1.29–3.64). Below normal neutrophil, lymphocyte, eosinophil and basophil counts were associated with higher risk of AAA with adjusted hazard ratio (95% CI) between 1.86 (1.04–3.35) and 1.62 (1.10–2.39).

Conclusions:

Higher neutrophil, monocyte, and eosinophil counts in midlife are associated with higher risk of AAA, even after accounting for traditional risk factors such as smoking, obesity, and atherosclerosis. This suggests the need to identify nontraditional risk factors and treatment strategies to mitigate the residual risk of AAA conferred by midlife inflammation. Whether immunosuppression is associated with higher risk of AAA needs further investigation.
Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects
Authors: Ronsein Graziella E. , Vaisar Tomas , Davidson W. Sean , Bornfeldt Karin E. , Probstfield Jeffrey L. , O’Brien Kevin D. , Zhao Xue-Qiao , Heinecke Jay W.
Published: June 2021

Objective:

Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides).

Approach and Results:

Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobin-related proteins;P≤0.0001 for each) in both the CPC and AIM-HIGH cohorts.

Conclusions:

The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides.

Registration:

URL:https://www.clinicaltrials.gov; Unique identifier: NCT00715273; NCT00880178; NCT00120289.
A Common Polymorphism in the
FADS1
Locus Links miR1908 to Low-Density Lipoprotein Cholesterol Through BMP1
Authors: Beehler Kaitlyn , Nikpay Majid , Lau Paulina , Dang Anh-Thu , Lagace Thomas A. , Soubeyrand Sébastien , McPherson Ruth
Published: June 2021

Objective:

Leveraging microRNA-Seq data and the 1000 Genomes imputed genotypes, we identified rs174561 as a strong microRNA quantitative trait loci for circulating microRNA-1908-5p with higher miR-1908-5p and reduced LDL (low-density lipoprotein)-cholesterol, fasting glucose and A1c concentrations in carriers of the rs-174561-C allele. Here, we have investigated the molecular mechanism(s) linking miR-1908-5p to LDL-C concentrations.

Approach and Results:

Transfection experiments demonstrate that the presence of the C allele significantly increases miR-1908-5p abundance relative to the T allele.
LDLR
mRNA and low-density lipoprotein receptor (LDLR) total protein were unchanged in response to differential miR-1908-5p expression. However, the ratio of the cleaved to full-length form of LDLR decreased with miR-1908-5p mimic and increased with miR-1908-5p inhibitor treatment. BMP1 (bone morphogenetic protein 1) is a protease responsible for LDLR cleavage, and we show that miR-1908-5p mimic reduces
BMP1
mRNA. Using a reporter array, we identified the TGF-β (transforming growth factor-beta) signaling pathway activity to be reduced by miR-1908-5p mimic treatment, and this was associated with reduced
TGFB1
expression. TGF-β signaling increases BMP1, and we further demonstrate that the effect of miR-1908-5p on LDLR cleavage is abolished by exogenous TGF-β treatment.

Conclusions:

These findings uncover a mechanism whereby miR-1908-5p reduces
TGFB1
abundance resulting in lower expression of
BMP1
, ultimately leading to reduced LDLR cleavage. Cleavage of the mature LDLR is known to reduce cell surface affinity for LDL, thereby linking miR-1908-5p to lower circulating LDL-cholesterol levels.
Comparison of In Vivo Tissue Temperature Profile and Lesion Geometry for Radiofrequency Ablation With High Power–Short Duration and Moderate Power–Moderate Duration: Effects of Thermal Latency and Contact Force on Lesion Formation
Authors: Nakagawa Hiroshi , Ikeda Atsushi , Sharma Tushar , Govari Assaf , Ashton John , Maffre Jennifer , Lifshitz Alexander , Fuimaono Kristine , Yokoyama Katsuaki , Wittkampf Fred H.M. , Jackman Warren M.
Published: June 2021

Background:

With short radiofrequency (RF) applications, tissue temperature continues to rise after RF termination (thermal latency), which may result in lesion growth after RF termination. The purpose was to compare in vivo tissue temperature profile (thermal latency), lesion size, and the incidence of steam pop and thrombus between RF ablation with very high power–very short RF (90 W/4 s), high power–short RF (50 W/10 s), and moderate power–moderate RF (30 W/30 s) in a canine thigh muscle preparation and beating heart.

Methods:

In the thigh muscle preparation (5 dogs), a 3.5-mm ablation electrode with 66 or 56 small irrigation holes (QDOT-Micro or ThermoCoolSmartTouch-SF, respectively) was held perpendicular or parallel to the muscle at 10
g
or 30
g
contact force. Total of 120 RFs were delivered at 90 W/4 s (QDOT catheter), 50 W/10 s, or 30 W/30 s (SF catheter). Electrode temperature, electrode-tissue interface temperature, and tissue temperatures at 3- and 7-mm depths were measured. In 6 closed-chest dogs, total of 72 RFs were delivered in the ventricle at 90 W/4 s, 50 W/10 s, or 30 W/30 s.

Results:

In the thigh muscle preparation, tissue temperatures and lesion size (depth, diameter, and volume) were the lowest/smallest for RFs at 90 W/4 s, followed by 50 W/10 s, and the greatest for 30 W/30 s. Thermal latency (Δtemperature and duration) was the greatest for RFs at 90 W/4 s, followed by 50 W/10 s, and the smallest for 30 W/30 s (
P
<0.01). Effective tissue heating (area under the curve ≥50 °C at 3-mm depth) was observed after RF termination in 88.0±7.6% with 90 W/4 s, 57.7±14.6% with 50 W/10 s, and only 31.9±8.5% with 30 W/30 s (
P
<0.01). In beating hearts, lesion size was also the smallest with 90 W/4 s and the greatest with 30 W/30 s RFs. Increasing contact force significantly increased lesion depth in all 3 groups. There was no significant difference in the incidence of steam pop or thrombus between 3 groups.

Conclusions:

Tissue temperatures and lesion size (depth, diameter, and volume) were the lowest/smallest for RF applications at 90 W/4 s, followed by 50 W/10 s, and the greatest for 30 W/30 s. The greater thermal latency for 90 W/4 s RF applications suggests that a significant portion of lesion is created after RF termination due to conductive tissue heating.
Educational environment amid COVID-19 pandemic: new security challenges
Authors: Baranova Victoria A. , Dubovskaya Ekaterina M. , Savina Olga O.
Published: June 2021

Background. of the article is determined by the need to study educational processes and the educational environment in the situation of the COVID-19 pandemic in particular. The objective of the study is to analyze the characteristics of the educational environment determined by the conditions of the COVID-19 pandemic and the requirements of self-isolation and distance learning, as well as psychological threats to the safety of the educational environment in these new conditions. Design A study of to the security of the educational environment in a pandemic was conducted. These threats were identified in an exploratory study in the first month of the self-isolation regime (April 2020). We analyzed information provided by junior psychology university students (n = 31); teachers (n = 19) and psychologists of Moscow schools (n = 6); schoolchildren – pupils of 5–7 grades (n = 76) and parents of schoolchildren (n = 18). All information was collected remotely, provided on condition of anonymity and voluntariness. Discourse processing was carried out by the method of content analysis and thematic analysis with subsequent expert assessment. The chosen methodological plan of qualitative research allowed the use of individual experiences as indicators of mass consciousness for the analysis of collective states. Results. It was revealed that the current situation created by the COVID-19 pandemic significantly changes the concept of «educational environment». The traditional characteristics of the school educational environment are complemented by factors resulting from the process of “expansion” and “shift” of the educational environment, on the one hand from the school environment to the home environment, and on the other hand from the offline format to the online format. The following new perspectives of the educational environment security defined by the situation of self-isolation are highlighted: distance learning; stay in a home environment, diminishing of direct communication; intensification of communication in the network; forced interaction with the immediate environment; the need to coordinate interaction between teachers and parents; the importance of Internet communication; dynamic processes in the family as in a small group, etc. Situations linked to the dynamics of family and interpersonal relationships, health, the physical environment at home, and the online format of the educational process cause the most important emotions in all participants of the educational process during self-isolation. Conclusions. The program of activities of the educational support service in the school environment should be supplemented with experience and new practices of life in isolation. In a situation of «expanded» educational space and distance learning, educational policy is obliged, while leaving school a priority, to take into account the emergence of new priority subjects in the educational environment that require attention.
Categorization of bodily sensations in psychodermatological disorders
Authors: Ermusheva Anastasia A. , Vinogradova Marina G. , Tkhostov Aleksander Sh.
Published: June 2021

Background. Categorization is one of the cognitive processes that ensure objects definition based on selected key features. Studying the aspects of categorization of bodily sensations allows to investigate the making sense of bodily sensations which seems promising in the context of exploring pathological bodily sensations. Objective: to study the aspects of categorization in psychodermatological disorders. Design. The study involved 113 patients with mental disorders with complaints of pathological bodily sensations (63 patients with psychodermatological disorders: delusional infestation (n = 33), neurotic excoriation (n = 30); 50 patients with depression with somatic symptoms). There were used the “Short Health Anxiety Inventory” and the psychosemantic method “Choice of descriptors of intraceptive sensations” with instructions: to choose bodily sensations of the healthy state, to classify sensations according to their similarity. Results. In psychodermatological disorders, health anxiety was lower in comparison to depression with somatic symptoms. The analysis of bodily sensations categorization of the healthy state revealed a significantly smaller descriptors number from classes of general somatic sensations, dynamics sensations, exteroceptive sensations and pleasant bodily sensations in psychodermatological disorders. In bodily sensations classification two general categories of bodily experience were distinguished: bodily sensations associated with the illness experience and bodily sensations of habitual functioning. Conclusion. Although there were the differences in health-anxiety and specificity of clinical manifestations in patients with mental disorders with complaints of pathological bodily sensations, the comparability of categorical structures of bodily experience was described, which manifested itself in features of general categories of bodily experience in psychodermatological disorders and depression with somatic symptoms.