bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Pathology Initiatives and Experience of a Large Academic Institution During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Lujan Giovanni M. , Savage Johanna , Shana'ah Arwa , Yearsley Martha , Thomas Diana , Allenby Patricia , Otero Jose , Limbach Abberly Lott , Cui Xiaoyan , Scarl Rachel T. , Hardy Tanner , Sheldon Jesse , Plaza Jose A. , Whitaker Bonnie , Frankel Wendy , Parwani Anil V. , Li Zaibo
Published: May 2021

Context.—

Pathology practices have begun integrating digital pathology tools into their routine workflow. During 2020, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic, causing a global health crisis that significantly affected the world population in several areas, including medical practice, and pathology was no exception.

Objective.—

To summarize our experience in implementing digital pathology for remote primary diagnosis, education, and research during this pandemic.

Design.—

We surveyed our pathologists (all subspecialized) and trainees to gather information about their use of digital pathology tools before and during the pandemic. Quality assurance and slide distribution data were also examined.

Results.—

During the pandemic, the widespread use of digital tools in our institution allowed a smooth transition of most clinical and academic activities into remote with no major disruptions. The number of pathologists using whole slide imaging (WSI) for primary diagnosis increased from 20 (62.5%) to 29 (90.6%) of a total of 32 pathologists, excluding renal pathology and hematopathology, during the pandemic. Furthermore, the number of pathologists exclusively using whole slide imaging for primary diagnosis also increased from 2 (6.3%) to 5 (15.6%) during the pandemic. In 35 (100%) survey responses from attending pathologists, 21 (60%) reported using whole slide imaging for remote primary diagnosis following the Centers for Medicare and Medicaid Services waiver. Of these 21 pathologists, 18 (86%) responded that if allowed, they will continue using whole slide imaging for remote primary diagnosis after the pandemic.

Conclusions.—

The pandemic served as a catalyst to pathologists adopting a digital workflow into their daily practice and realizing the logistic and technical advantages of such tools.
Some Reactive Lesions of Bone Are Probably Neoplasms
Authors: Memon Raima A. , Wei Shi , Siegal Gene P.
Published: May 2021

Context.—

A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically been thought to be reactive lesions. However, modern molecular techniques when supplementing clinical, radiographic, and histologic evaluation suggest they may, in fact, be neoplasms.

Objective.—

To review the clinical presentation and histopathologic, molecular, and radiologic features of selective bone lesions, focusing most specifically on subungual exostosis, florid reactive periostitis, and bizarre periosteal osteochondromatous proliferation.

Data Sources.—

Literature review and personal experience are the sources of this review.

Conclusions.—

Some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities, and thus may be neoplasms. Although most common in the bones of the fingers and toes, these lesions also occur in long and other bones. The clinical presentations, radiologic appearances, and histopathologic features often overlap, making the diagnosis challenging, and these lesions may require molecular evaluation to maximize accurate prognostication.
Recensiones//Book reviews
Authors: Moraleda Ruano Álvaro
Published: May 2021

Ibáñez-Martín, J.A. (2017). Horizontes para los educadores: Las profesiones educativas y la promoción de la plenitud humana. Dykinson, 271 páginas. ISBN: 978-84-9148-163-8. DL: M-9009-2017
Escribir en sueños. Zambrano, Derrida y la temporalidad de la novela
Authors: Valls Boix Juan Evaristo
Published: May 2021

El propósito del presente estudio consiste en pensar la ambivalencia con que Zambrano aborda el género de la novela. De un lado, las reflexiones en La confesión, género literario posicionan a Zambrano próxima a las críticas de Benjamin y Adorno a propósito de la cosificación de la novela como género burgués de consumo. De otro lado, sus exposiciones en El sueño creador conciben la novela como la actualización del sueño de la libertad mediante el que el hombre pensarse desbordando la medida de lo humano. Esta ambivalencia del género revela el relato como la condición de posibilidad e imposibilidad de una temporalidad incalculable, no cuantitativa, lo que vinculará las reflexiones de Zambrano con el pensamiento de Derrida.

The aim of this study is to think the ambivalence with which Zambrano tackles the novel’s gender. On the one side, her thesis in La confesión, género literario bring Zambrano closer to Benjamin, and Adorno’s critique to the novel as a bourgeois and consumable gender. On the other side, Zambrano’s statements in El sueño creador depict the novel as the fulfillment of a dream of freedom, where man can question himself beyond the limits of the human. In this ambivalence, the narrative gender shows both the conditions of possibility and the conditions of impossibility of a non-quantitative temporality. This aporetic character of the novel opens a discussion between Zambrano and Derrida’s thought.
Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway
Authors: Dinh Tra Thi Huong , Iseki Hiroyoshi , Mizuno Seiya , Iijima-Mizuno Saori , Tanimoto Yoko , Daitoku Yoko , Kato Kanako , Hamada Yuko , Hasan Ammar Shaker Hamed , Suzuki Hayate , Murata Kazuya , Muratani Masafumi , Ema Masatsugu , Kim Jun-Dal , Ishida Junji , Fukamizu Akiyoshi , Kato Mitsuyasu , Takahashi Satoru , Yagami Ken-ichi , Wilson Valerie , Arkell Ruth M , Sugiyama Fumihiro
Published: May 2021

In vivo function of CDK5 and Abl enzyme substrate 2 (Cables2), belonging to the Cables protein family, is unknown. Here, we found that targeted disruption of the entireCables2locus (Cables2d) caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption ofCables2, 50% down-regulation ofRps21abutting on theCables2locus, and up-regulation of p53-target genes inCables2dgastrulas. We further revealed the lethality phenotype inRps21-deleted mice and unexpectedly, the exon 1-deletedCables2mice survived. Interestingly, chimeric mice derived fromCables2dESCs carrying exogenousCables2and tetraploid wild-type embryo overcame gastrulation. These results suggest that the diminished expression ofRps21and the completed lack ofCables2expression are intricately involved in the embryonic lethality via the p53 pathway. This study sheds light on the importance ofCables2locus in mouse embryonic development.
Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis
Authors: Zhou Xin , Shin Seula , He Chenxi , Zhang Qiang , Rasband Matthew N , Ren Jiangong , Dai Congxin , Zorrilla-Veloz Rocío I , Shingu Takashi , Yuan Liang , Wang Yunfei , Chen Yiwen , Lan Fei , Hu Jian
Published: May 2021

Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol biosynthesis in oligodendrocytes remain elusive. In the present study, we found that Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice resulted in impaired cholesterol biosynthesis and defective myelinogenesis without compromising their differentiation into Aspa+Gstpi+ myelinating oligodendrocytes. Mechanistically, Qki-5 functions as a co-activator of Srebp2 to control transcription of the genes involved in cholesterol biosynthesis in oligodendrocytes. Consequently, Qki depletion led to substantially reduced concentration of cholesterol in mouse brain, impairing proper myelin assembly. Our study demonstrated that Qki-Srebp2-controlled cholesterol biosynthesis is indispensable for myelinogenesis and highlights a novel function of Qki as a transcriptional co-activator beyond its canonical function as an RNA-binding protein.
Linguistic processing of task-irrelevant speech at a cocktail party
Authors: Har-shai Yahav Paz , Zion Golumbic Elana
Published: May 2021

Paying attention to one speaker in a noisy place can be extremely difficult, because to-be-attended and task-irrelevant speech compete for processing resources. We tested whether this competition is restricted to acoustic-phonetic interference or if it extends to competition for linguistic processing as well. Neural activity was recorded using Magnetoencephalography as human participants were instructed to attend to natural speech presented to one ear, and task-irrelevant stimuli were presented to the other. Task-irrelevant stimuli consisted either of random sequences of syllables, or syllables structured to form coherent sentences, using hierarchical frequency-tagging. We find that the phrasal structure of structured task-irrelevant stimuli was represented in the neural response in left inferior frontal and posterior parietal regions, indicating that selective attention does not fully eliminate linguistic processing of task-irrelevant speech. Additionally, neural tracking of to-be-attended speech in left inferior frontal regions was enhanced when competing with structured task-irrelevant stimuli, suggesting inherent competition between them for linguistic processing.
OPA1 deletion in brown adipose tissue improves thermoregulation and systemic metabolism via FGF21
Authors: Pereira Renata O , Marti Alex , Olvera Angela Crystal , Tadinada Satya Murthy , Bjorkman Sarah Hartwick , Weatherford Eric Thomas , Morgan Donald A , Westphal Michael , Patel Pooja H , Kirby Ana Karina , Hewezi Rana , Bùi Trân William , García-Peña Luis Miguel , Souvenir Rhonda A , Mittal Monika , Adams Christopher M , Rahmouni Kamal , Potthoff Matthew J , Abel E Dale
Published: May 2021

Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, which is activated independently of BAT thermogenic function.
Mapping single-cell atlases throughout Metazoa unravels cell type evolution
Authors: Tarashansky Alexander J , Musser Jacob M , Khariton Margarita , Li Pengyang , Arendt Detlev , Quake Stephen R , Wang Bo
Published: May 2021

Comparing single-cell transcriptomic atlases from diverse organisms can elucidate the origins of cellular diversity and assist the annotation of new cell atlases. Yet, comparison between distant relatives is hindered by complex gene histories and diversifications in expression programs. Previously, we introduced the self-assembling manifold (SAM) algorithm to robustly reconstruct manifolds from single-cell data (Tarashansky et al., 2019). Here, we build on SAM to map cell atlas manifolds across species. This new method, SAMap, identifies homologous cell types with shared expression programs across distant species within phyla, even in complex examples where homologous tissues emerge from distinct germ layers. SAMap also finds many genes with more similar expression to their paralogs than their orthologs, suggesting paralog substitution may be more common in evolution than previously appreciated. Lastly, comparing species across animal phyla, spanning sponge to mouse, reveals ancient contractile and stem cell families, which may have arisen early in animal evolution.
In-network generalized trustworthy data collection for event detection in cyber-physical systems
Authors: Ur Rahman Hafiz , Wang Guojun , Alam Bhuiyan Md Zakirul , Chen Jianer
Published: May 2021

Sensors in Cyber-Physical Systems (CPS) are typically used to collect various aspects of the region of interest and transmit the data towards upstream nodes for further processing. However, data collection in CPS is often unreliable due to severe resource constraints (e.g., bandwidth and energy), environmental impacts (e.g., equipment faults and noises), and security concerns. Besides, detecting an event through the aggregation in CPS can be intricate and untrustworthy if the sensor's data is not validated during data acquisition, before transmission, and before aggregation. This paper introduces In-network Generalized Trustworthy Data Collection (IGTDC) framework for event detection in CPS. This framework facilitates reliable data for aggregation at the edge of CPS. The main idea of IGTDC is to enable a sensor's module to examine locally whether the event's acquired data is trustworthy before transmitting towards the upstream nodes. It further validates whether the received data can be trusted or not before data aggregation at the sink node. Additionally, IGTDC helps to identify faulty sensors. For reliable event detection, we use collaborative IoT tactics, gate-level modeling with Verilog User Defined Primitive (UDP), and Programmable Logic Device (PLD) to ensure that the event's acquired data is reliable before transmitting towards the upstream nodes. We employ Gray code in gate-level modeling. It helps to ensure that the received data is reliable. Gray code also helps to distinguish a faulty sensor. Through simulation and extensive performance analysis, we demonstrate that the collected data in the IGTDC framework is reliable and can be used in the majority of CPS applications.
Efficient VANET safety message delivery and authenticity with privacy preservation
Authors: Mohamed Taha M. , Ahmed Islam Z. , Sadek Rowayda A.
Published: May 2021

Vehicular ad-hoc networks (VANETs) play an essential role in the development of the intelligent transportation system (ITS). VANET supports many types of applications that have strict time constraints. The communication and computational overheads are minimal for these computations and there are many security requirements that should be maintained. We propose an efficient message authentication system with a privacy preservation protocol. This protocol reduces the overall communication and computational overheads. The proposed protocol consists of three main phases: the group registration phase, send/receive messages phase, and the leave/join phase. For cryptography algorithms, we combined symmetric and asymmetric key algorithms. The symmetric key was generated and exchanged without using the Diffie–Hellman (DH) protocol. Furthermore, we used an efficient version of the RSA algorithm called CRT-RSA. The experimental results showed that the computational overhead in the registration phase was significantly reduced by 91.7%. The computational overhead for sending and receiving the non-safety message phase was reduced by 41.2% compared to other existed protocols. Moreover, our results showed that the time required to broadcast a safety and non-safety group message was below 100 ms and 150 ms, respectively. The average computational time of sending and receiving a one-to-one message was also calculated. The proposed protocol was also evaluated with respect to performance and security and was shown to be invulnerable to many security attacks.
Departmental Preference Reason and Satisfaction Level of Political Science and Public Administration Students in Turkey
Authors: AGALLIJA Nikolin
Published: May 2021

Kişinin çalışması, ihtiyaçlarını karşılamak için bir gelirinin olması, yani bir mesleğe sahip olması giderilmesi gereken temel ihtiyaçlardan biridir. Bu temel ihtiyacın giderilmesi sonrası sosyalleşme ve kendini gerçekleştirme gibi
diğer gereksinimler ortaya çıkmaktadır. Bireyler, temel ihtiyaçlarının gidermek maksadıyla belli bir mesleğe sahip olabilmek için uzun ve yoğun bir eğitim sürecini yaşamakta ve bu çaba sonucunda mesleğini elde edebilmektedir. Kişinin
hayatını idame ettirebileceği geliri sağlayabilmesi mesleğini elde etme süreci sonrası gerçekleşmektedir. İnsan hayatının bu kısmı, ömrünün yaklaşık 30-40 yıllık bir bölümüne tekabül etmektedir. İnsanın mesleğini icra ettiği veya
çalıştığı 30-40 yıllık dönem dikkate alındığında, seçilen mesleğin hem ekonomik kazanımlar hem de psikolojik açıdan tatmin edici olması beklenmektedir. Bu çalışmada, siyaset bilimi ve kamu yönetimi bölümlerini seçen öğrencilerin,
tercihlerinde etkili olan faktörlerle; okudukları üniversite ve bölüme ilişkin memnuniyetleri ve gelecek beklentilerinin ortaya konulması amaçlanmıştır. Bu hedef doğrultusunda, 2018-2019 öğretim yılında Siyaset Bilimi ve Kamu Yönetimi
bölümü öğrencilerinin, tercih nedenleri; geleceğe ilişkin duygu ve düşüncelerini ortaya koymak için 600 öğrenciye bir araştırma yürütülmüştür. Araştırma sonucunda öğrencilerin okudukları üniversite ve bölümden kısmi düzeyde memnun
oldukları, bölüm seçme nedenlerinin mezun olunan lise, cinsiyet ve sosyo ekonomik düzeye göre farklılaştığı ortaya çıkmıştır. Araştırmaya katılan öğrencilerin, mezuniyet sonrası kısa sürede iş bulma konusunda umutlu olmadıkları
sonucuna ulaşılmıştır. Araştırma bulguları doğrultusunda öneriler sunulmuştur.
Water Quality of Pond Irrigation ChannelsBased on the Community Structure of Macrozoobenthosin Legonkulon,Subang, West Java
Authors: Adelianti Atiek , Hamdani Herman , Pratama RuskyIntan , Herawati Heti
Published: May 2021

This research aimed to analyze the quality of water in pond irrigation channels by examining the community structure of macrozoobenthos in Legonkulon, Subang Regency, West Java. The research was conducted in the Pond Irrigation Channels, Subang Regency, West Java starting from July until September 2020. This research method used a survey method using primary data in the form of physical chemistry of aquatic data, macrozoobenthos density, diversity index, uniformity index. The method used in data collecting techniques was purposive sampling in determining 4 stations and 3 repetitions. Data analysis in this research used descriptive analysis. Research results found 28 species consisting of 3 phyla, namely Mollusca, Arthropoda, and Annelida. The species that dominate the four stations are Filopaludinajavanica and Tarebiagranifera. Makrozoobenthos density ranges from 40 – 295 ind/m2. Makrozoobenthos diversity index in the medium category 1.0 < H’ <3.322. Uniformity values ranged from 0,43 to 0,81 with low to high category. The highest uniformity index was found at station 3, and the lowest uniformity index was at station 4, while at station 1 and station 2 had a moderate uniformity index. The results of the macrozoobenthos community structure showed that the water quality of the pond irrigation channels in Legonkulon was classified as being medium polluted.
Experience and Perceptions of Medical and Dental Interns on the Effects of the COVID- 19 Pandemic on their Internship Program- A Questionnaire Based Study in Makkah Region of Saudi Arabia
Authors: Shetty Karunakar , Wali Othman , M. Maleh Abdulaziz Talal , Alharthi Zaid Naif , Zahran Mahmoud Hani , Khairudein Maged Mhmdnzar
Published: May 2021

Introduction: COVID-19 is a highly infectious disease caused by an RNA virus belonging to a large family of coronaviruses. WHO declared COVID-19 as a public health emergency and classified it as a pandemic. The COVID-19 pandemic affected the medical education globally.

Aim of the Study: The aim of the study is to evaluate the impact of COVID-19 on the internship program.

Materials and Methods: A cross‑sectional study was conducted among the medical and dental students of various universities in Makkah region of Saudi Arabia. A questionnaire consisting of 15 close ended, pre-tested questions was developed to determine the experiences and perceptions of medical and dental interns due to COVID-19. The data were tabulated and analyzed using SPSS version 21. Chi-square test was used to assess the experiences and perceptions among the Medical and Dental interns. P-value of less than 0.05 was considered statistically significant. Results: The study included 453 participants, out of which 253 were dental interns and 200 were medical interns. 231 (51%) of male interns participated in this study and 222 (49%) female interns participated. 140 (55.6%) and 138 (69.3%) of the participants of the dental and medical interns respectively felt COVID-19 affected options to select specialties of their interest for post-graduation, whereas, 112 (44.4%) and 61 (30.7%) of the dental and medical interns felt other way. Conclusion: Majority of the participants reported that COVID-19 did not affect them psychologically. In addition, most of the medical and dental interns felt covid -19 affected opinions to select specialties of their interest for post-graduation.
Factors related to infection by klebsiella pneumoniae in a private hospital / Fatores relacionados a infecçao por klebsiella pneumoniae em um hospital privado
Authors: Santana Rosane da Silva , Silva Naiana Maria Diogo da , Sousa Teresa Raquel de Carvalho Castro , Dias Samya Raquel Soares , Silva Igor Almeida , Silva Aline dos Santos
Published: May 2021

Objetivo: identificar a prevalência de klebsiella pneumoniae e analisar os fatores relacionados à infecção por essa bactéria em hospital privado do nordeste brasileiro. Método: estudo descritivo retrospectivo documental, realizado com pacientes que desenvolveram infecção no ano de 2017 (n:64). Coletou-se informações sociodemográficas e referentes a infecção. Os dados foram processados no SPSS 20.0. O projeto foi aprovado pelo comitê de ética. Resultados: o sítio topográfico mais prevalente foi o trato urinário (34;56,7%). o principal fator de risco para desencadear infecção por klebsiella pneumoniae foi a utilização de ventilação mecânica, apresentando risco de 43,8% para o aparecimento de infecções por esse microrganismo. Maior resistência foi encontrada para o antimicrobiano piperacilina/tazobactam 52 (82,5%). Conclusão: Pela alta resistência aos antibióticos e o grande potencial de contaminação da klebsiella, medidas devem ser adotadas para minimizar o alto nível de contaminação e, principalmente do prognóstico negativo para paciente.
Syndrome of susceptibility assessment in burnout nurses acting in oncohematologia / Avaliação da susceptibilidade da síndrome de burnout em enfermeiros oncohematológicos
Authors: Barros Angela Maria Melo Sá , Santos Geovana Rodrigues , Oliveira Naédia Vitória Santos , Santos Ianka Heloisa Alencar , Andrade Thandara Rejane Santos Ferreira , Cavalcante Anderson Batista
Published: May 2021

Objetivo: Investigar a ocorrência da Síndrome de Burnout em enfermeiros da unidade de oncohematologia no serviço de referência do Hospital de Urgência de Sergipe.Método: Trata-se de um estudo descritivo quantitativo, realizado com 16 enfermeiros voluntários. Utilizou-se um questionário validado, estruturado e autoaplicável, acrescido do instrumento MaslachBurnoutInventory. A análise dos dados foi feita por meio da ferramenta Epiinfo 7.2.Resultados:Evidenciou-se que 43,75% dos enfermeiros encontram-se na fase inicial da Síndrome de Burnout. Outros 37,5% encontram-se com a possibilidade de desenvolver a mesma, e que18,75% dos enfermeiros participantes apresentam sinais do sofrimento caracterizado por tal agravo.Conclusão:A academia representa uma parcela mobilizadora da sociedade. Faz-se importante, que pesquisas venham discutir e apresentar resultados que sensibilizem a necessidade urgente de tratativa dessa temática, a partir de ações conjuntas que possam intervir no sentido da saúde desses trabalhadores.
Health self-perception of primary care users / Autopercepção de saúde de usuárias da atenção primária
Authors: Lima Eliane de Fatima Almeida , Costa Leite Franciele Marabotti , Storari Silva Juliane Almeida , Luis Mayara Alves , Batista Karla de Melo
Published: May 2021

Objetivo: Determinar a autopercepção de saúde de usuárias da atenção primária e verificar a associação com fatores socioeconômicos, clínicos e experiência de violência. Métodos: Estudo epidemiológico, analítico, do tipo transversal realizado com 991 mulheres em 26 Unidades Básica de Vitória, Espirito Santo. Variáveis socioeconômicas, clínicas, de percepção de saúde, e, as experiências de violência praticada pelo parceiro íntimo ao longo da vida foram utilizadas nas análises dos dados.  Teste de Regressão de Poisson para análise multivariada foi utilizada para obtenção das razões de prevalência, sendo o ajuste das variáveis realizado pelo método tipo backward, tendo por base o modelo hierárquico. Resultados: Mulheres com 40 anos ou mais, não brancas, com escolaridade de até quatro anos, evangélicas e sem trabalho remunerado percebem mais frequentemente a saúde negativamente. Conclusões: Características socioeconômicas, clínicas e de experiência de violência por parceiro íntimo podem contribuir para percepção negativa da saúde.
Interventions for bearers of non-communicable chronic diseases: experience report and epidemiological study / Intervenções para portadores de doenças crônicas não-transmissíveis: relato de experiência e estudo epidemiológico
Authors: Regne Giulia Ribeiro Schettino , Meireles Marivania Queiroz , Faria Alessandra Lage , Balena Helen Carine Ferreira , De Souza Érica Moreira , Matozinhos Fernanda Penido
Published: May 2021

Objetivo: Descrever a implementação de atividades de promoção da saúde e prevenção de agravos para portadores de doenças crônicas não-transmissíveis, além de estimar a associação entre hábitos de saúde e de vida e os sexos. Método: Relato de experiência e estudo quantitativo transversal, realizado com portadores de doenças crônicas não-transmissíveis. Os dados sociodemográficos, de estado de saúde e hábitos de vida foram submetidos à análise estatística por meio dos testes T-student e Qui-quadrado. Resultados: Houve diferença estatisticamente significativa entre os valores de pressão arterial sistólica segundo o sexo. Nas atividades, os participantes foram participativos, apresentando avaliações positivas. Conclusão: As ações educativas e interventivas contribuem para a troca de saberes científicos e populares. As ações em saúde devem ser integrais e direcionadas, também, ao público masculino.
Empirical indicators of cardiovascular rehabilitation behind Roy adaptive model / Indicadores empíricos da reabilitação cardiovascular sob a otica do modelo adaptativo de Roy
Authors: FARIAS MARIA SINARA , SILVA LÚCIA DE FÁTIMA DA
Published: May 2021

Objetivo: identificar, da literatura científica, os indicadores empíricos da Reabilitação cardiovascular organizados conformes nos modos adaptativos do Modelo de Adaptação de Roy. Método: trata-se de um estudo de revisão integrativa, realizado nas bases de dados Scientific Electronic Library Online (SCIELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Base de dados em Enfermagem (BDENF), PUBMED e Sistema Online de Busca e Análise de Literatura Médica (MEDLINE), utilizando os descritores “Cardiovascular Rehabilitation”; “Nursing” conectados pelo operador booleano and. Foram incluídos 42 estudos, todos foram lidos na íntegra e sintetizados conforme os modos adaptativos de Roy. Resultados: os estudos analisados apresentam indicadores empíricos da reabilitação cardiovascular que se configuram no modo Fisiológico, de autoconceito, desempenho de papel e de interdependência, a fim de contribuir para a autonomia do sujeito e avanço da ciência Enfermagem. Conclusão: possibilitou um resgate do conhecimento teórico em relação ao processo de Reabilitação Cardiovascular.
Factors associated with daytime sleepiness in medical students / Fatores associados à sonolência diurna em estudantes de medicina
Authors: Barbosa-Medeiros Mirna Rossi , Figueiredo Janinny Fernanda Lopes Mendes , Melo Liliane de Oliveira , Rossi-Barbosa Luiza Augusta Rosa , Caldeira Antonio Prates
Published: May 2021

Objetivo: Avaliar os fatores associados à sonolência diurna em graduandos do curso de medicina das três faculdades do Norte de Minas. Método: Estudo transversal, realizado com 231 acadêmicos que estavam frequentando o primeiro, sétimo e décimo-primeiro períodos de graduação em medicina em 2015. A sonolência diurna foi avaliada pelo instrumento Escala de Sonolência Diurna de Epworth. Realizou-se a análise de regressão de Poisson para verificar os fatores associados à sonolência diurna. Resultados: Níveis patológicos e muito patológicos de sonolência diurna foram observados, respectivamente, em 34,6% e 6,9% dos estudantes. A prevalência de sonolência diurna foi maior nos estudantes com Transtornos Mentais Comuns, Exaustão Emocional e Ineficácia Profissional, e menor naqueles que residem com os pais. Conclusão: A prevalência de sonolência diurna patológica nos estudantes mostrou-se elevada, e teve relação com transtornos mentais comuns, percepção de exaustão emocional e profissional, além do contexto com quem o estudante residia.
The ZEB2‐dependent EMT transcriptional programme drives therapy resistance by activating nucleotide excision repair genes ERCC1 and ERCC4 in colorectal cancer
Authors: Sreekumar Rahul , Al‐Saihati Hajir , Emaduddin Muhammad , Moutasim Karwan , Mellone Massimiliano , Patel Ashish , Kilic Seval , Cetin Metin , Erdemir Sule , Navio Marta Salgado , Lopez Maria Antonette , Curtis Nathan , Yagci Tamer , Primrose John N. , Price Brendan D. , Berx Geert , Thomas Gareth J. , Tulchinsky Eugene , Mirnezami Alex , Sayan A. Emre
Published: May 2021

Resistance to adjuvant chemotherapy is a major clinical problem in the treatment of colorectal cancer (CRC). The aim of this study was to elucidate the role of an epithelial to mesenchymal transition (EMT)‐inducing protein, ZEB2, in chemoresistance of CRC, and to uncover the underlying mechanism. We performed IHC for ZEB2 and association analyses with clinical outcomes on primary CRC and matched CRC liver metastases in compliance with observational biomarker study guidelines. ZEB2 expression in primary tumours was an independent prognostic marker of reduced overall survival and disease‐free survival in patients who received adjuvant FOLFOX chemotherapy. ZEB2 expression was retained in 96% of liver metastases. The ZEB2‐dependent EMT transcriptional programme activated nucleotide excision repair (NER) pathway largely via upregulation of the ERCC1 gene and other components in NER pathway, leading to enhanced viability of CRC cells upon oxaliplatin treatment. ERCC1‐overexpressing CRC cells did not respond to oxaliplatin in vivo, as assessed using a murine orthotopic model in a randomised and blinded preclinical study. Our findings show that ZEB2 is a biomarker of tumour response to chemotherapy and risk of recurrence in CRC patients. We propose that the ZEB2‐ERCC1 axis is a key determinant of chemoresistance in CRC.
Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
Authors: Lee Sol Ji , Choi Yu‐Jeong , Kim Hyo In , Moon Hyo Eun , Paek Sun Ha , Kim Tai Young , Ko Seong‐Gyu
Published: May 2021

Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann‐Pick C1 (NPC1), which exports low‐density lipoprotein (LDL)‐derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR‐overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD‐induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti‐GBM drug by disrupting cholesterol trafficking and autophagy.
SENP3 loss promotes M2 macrophage polarization and breast cancer progression
Authors: Xiao Ming , Bian Qi , Lao Yimin , Yi Jing , Sun Xueqing , Sun Xuxu , Yang Jie
Published: May 2021

Tumor‐associated macrophages (TAM) play a crucial role in promoting cancer progression. Upon cytokine stimulation, TAM preferentially polarize to the anti‐inflammatory and pro‐tumor M2 subtype. The mechanism underlying such preferential polarization remains elusive. Here, we report that macrophage‐specific deletion of the SUMO‐specific protease Sentrin/SUMO‐specific protease 3 promotes macrophage polarization towards M2 in bone marrow‐derived macrophage (BMDM) induced by interleukin 4 (IL‐4)/IL‐13 and in an ex vivo model (murine Py8119 cell line), as well as in a mouse orthotopic tumor model. Notably, Sentrin/SUMO‐specific protease 3 (SENP3) loss in macrophages accelerated breast cancer malignancy in ex vivo and in vivo models. Mechanistically, we identified Akt Serine/threonine kinase 1 (Akt1) as the substrate of SENP3 and found that the enhanced Akt1 SUMOylation upon SENP3 loss resulted in Akt1 hyper‐phosphorylation and activation, which facilitates M2 polarization. Analysis of clinical data showed that a lower level of SENP3 in TAM has a strong negative correlation with the level of the M2 marker CD206, as well as with a worse clinical outcome. Thus, increased Akt1 SUMOylation as a result of SENP3 deficiency modulates polarization of macrophages to the M2 subtype within a breast cancer microenvironment, which in turn promotes tumor progression.
Phosphorylation of the androgen receptor at Ser81 is co‐sustained by CDK1 and CDK9 and leads to AR‐mediated transactivation in prostate cancer
Authors: Gao XinTao , Liang Jiaqian , Wang LiYang , Zhang Zhaoyang , Yuan Penghui , Wang Jiaxin , Gao Yanfei , Ma Fen , Calagua Carla , Ye Huihui , Voznesensky Olga , Wang Shaogang , Wang Tao , Liu Jihong , Chen Shaoyong , Liu Xiaming
Published: May 2021

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re‐activation still remains a major challenge during treatment of castration‐resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81‐phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR‐mediated transactivation with the chromatin locus openness. Moreover, pS81‐specific ChIP‐Seq showed a disproportional occupancy of pS81 on AR‐activated promoters, while 3C‐ChIP assays further indicated an enrichment of pS81 at the PSA enhancer‐promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re‐ChIP assays also confirmed that AR‐dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin‐bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.
Protease‐activated receptor 1 drives and maintains ductal cell fates in the premalignant pancreas and ductal adenocarcinoma
Authors: Tekin Cansu , Scicluna Brendon P. , Lodestijn Sophie C. , Shi Kun , Bijlsma Maarten F. , Spek C. Arnold
Published: May 2021

Pancreatic acinar cells have high plasticity and can transdifferentiate into ductal‐like cells. This acinar‐to‐ductal metaplasia (ADM) contributes to tissue maintenance but may also contribute to the premalignant transformation that can eventually progress to pancreatic ductal adenocarcinoma (PDAC). Macrophages are key players in ADM, and macrophage‐secreted matrix metalloproteinase (MMP)‐9 induces ADM through yet unknown mechanisms. As we previously identified MMP9 as a novel agonist of protease‐activated receptor 1 (PAR1), a receptor that is known to orchestrate the cross‐talk between macrophages and tumor cells in PDAC, we here assessed the contribution of PAR1 to pancreatic cell fates. We found that genetic deficiency for PAR1 increases acinar gene expression programs in the healthy pancreas and that PAR1 deficiency limits ductal transdifferentiation in experimental systems for ADM. Moreover, PAR1 silencing in PDAC cells increases acinar marker expression. Changes in PDAC cell lines were associated with a downregulation of known Myc‐target genes, and Myc inhibition mimics PAR1 deficiency in enhancing acinar programs in healthy organoids and PDAC cells. Overall, we identify the PAR1‐Myc axis as a driver of ductal cell fates in premalignant pancreas and PDAC. Moreover, we show that cellular plasticity is not unique to acinar cells and that ductal regeneration into acinar‐like cells is possible even in the context of oncogenic KRAS activation.
The miR‐223/nuclear factor I‐A axis regulates inflammation and cellular functions in intestinal tissues with necrotizing enterocolitis
Authors: Wu Yu Zheng , Chan Kathy Yuen Yee , Leung Kam Tong , Lam Hugh Simon , Tam Yuk Him , Lee Kim Hung , Li Karen , Ng Pak Cheung
Published: May 2021

We previously demonstrated that microRNA(miR)‐223 is overexpressed in intestinal tissue of infants with necrotizing enterocolitis (NEC). The objective of the current study was to identify the target gene of miR‐223 and to investigate the role of the miR‐223/nuclear factor I‐A (NFIA) axis in cellular functions that underpin the pathophysiology of NEC. The target gene of miR‐223 was identified by in silico target prediction bioinformatics, luciferase assay, and western blotting. We investigated downstream signals of miR‐223 and cellular functions by overexpressing the miRNA in Caco‐2 and FHs74 cells stimulated with lipopolysaccharide or lipoteichoic acid (LTA). NFIA was identified as a target gene of miR‐223. Overexpression of miR‐223 significantly induced MYOM1 and inhibited NFIA and RGN in Caco‐2 cells, while costimulation with LTA decreased expression of GNA11, MYLK, and PRKCZ. Expression levels of GNA11, MYLK, IL‐6, and IL‐8 were increased, and levels of NFIA and RGN were decreased in FHs74 cells. These potential downstream genes were significantly correlated with levels of miR‐223 or NFIA in primary NEC tissues. Overexpression of miR‐223 significantly increased apoptosis of Caco‐2 and FHs74 cells, while proliferation of FHs74 was inhibited. These results suggest that upon binding with NFIA, miR‐223 regulates functional effectors in pathways of apoptosis, cell proliferation, G protein signaling, inflammation, and smooth muscle contraction. The miR‐223/NFIA axis may play an important role in the pathophysiology of NEC by enhancing inflammation and tissue damage.
METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia
Authors: Pan Zhi‐peng , Wang Bin , Hou Di‐yu , You Ruo‐lan , Wang Xiao‐ting , Xie Wen‐hui , Huang Hui‐fang
Published: May 2021

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML‐MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m6A epigenetic changes in MSCs determined via RIP‐qPCR and MeRIP‐qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m6A modification of AKT1‐mRNA. Downregulated METTL3 expression in AML‐MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.
Three‐dimensional structures of avian beta‐microseminoproteins: insight from the chicken egg‐specific beta‐microseminoprotein 3 paralog
Authors: Coste Franck , Moreau Thierry , Labas Valérie , Chessé Magali , Bregeon Mégane , Meudal Hervé , Loth Karine , Castaing Bertrand , Guyot Nicolas , Réhault‐Godbert Sophie
Published: May 2021

Beta‐microseminoproteins (MSMBs) are small disulfide‐rich proteins that are conserved among vertebrates. These proteins exhibit diverse biological activities and were mainly reported to play a role in male fertility, immunity, and embryogenesis. In this work, we focused on the chicken MSMB3 protein that was previously depicted as an egg antibacterial protein. We report that MSMB3 protein is exclusively expressed in the reproductive tissues of laying hens (in contrast to chicken MSMB1 and MSMB2 paralogs), to be incorporated in the egg white during the process of egg formation. We also showed that chicken MSMB3 possesses highly conserved orthologs in bird species, including Neognathae and Palaeognathae. Chicken MSMB3 was purified from egg white using heparin affinity chromatography and was analyzed by top‐down and bottom‐up proteomics. Several proteoforms could be characterized, and a homodimer was further evidenced by NMR spectroscopy. The X‐ray structure of chicken MSMB3 was solved for the first time, revealing that this protein adopts a novel dimeric arrangement. The highly cationic MSMB3 protein exhibits a distinct electrostatic distribution compared with chicken MSMB1 and MSMB2 structural models, and with published mammalian MSMB structures. The specific incorporation of MSMB3 paralog in the egg, and its phylogenetic conservation in birds together with its peculiar homodimer arrangement and physicochemical properties, suggests that the MSMB3 protein has evolved to play a critical role during the embryonic development of avian species. These new data are likely to stimulate research to elucidate the structure/function relationships of MSMB paralogs and orthologs in the animal kingdom.
Identification of crucial noncoding RNAs and mRNAs in hypertrophic scars via RNA sequencing
Authors: Li Xiaodong , He Zeliang , Zhang Julei , Han Yan
Published: May 2021

Hypertrophic scarring (HS) is a dermal fibroproliferative disorder characterized by excessive deposition of collagen and other extracellular matrix components. The aim of this study is to explore crucial long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) associated with HS and provide a better understanding of the molecular mechanism of HS. To investigate the lncRNA, circRNA and mRNA expression profiles, we performed RNA sequencing of human HS and normal skin tissues. After the identification of differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and circRNAs (DEcircRNAs), we performed functional enrichment of DEmRNAs. Further on, we constructed DElncRNA/DEcircRNA–DEmRNA coexpression networks and competing endogenous RNA regulatory networks, and performed functional analyses of the DEmRNAs in the constructed networks. In total, 487 DEmRNAs, 92 DElncRNAs and 17 DEcircRNAs were identified. DEmRNAs were significantly enriched in processes such as collagen fibril organization, extracellular matrix–receptor interaction and the phosphatidylinositol 3‐kinase (PI3K)–Akt signaling pathway. In addition, we detected 580 DElncRNA–DEmRNA and 505 DEcircRNA–DEmRNA coexpression pairs. The competing endogenous RNA network contained 18 circRNA–microRNA (miRNA) pairs, 18 lncRNA–miRNA pairs and 409 miRNA–mRNA pairs, including 10 circRNAs, 5 lncRNAs, 15 miRNAs and 160 mRNAs. We concluded that MIR503HG/hsa‐miR‐204‐3p/ACAN, MIR503HG/hsa‐miR‐431‐5p/TNFRSF9, MEG3/hsa‐miR‐6884‐5p/ADAMTS14, AC000035.1‐ADAMTS14 and hsa_circ_0069865‐COMP/ADAM12 interaction pairs may play a central role in HS.
Transfer of stabilising mutations between different secondary active transporter families
Authors: Cecchetti Cristina , Scull Nicola J. , Mohan Thotegowdanapalya C. , Alguel Yilmaz , Jones Alexandra M. C. , Cameron Alexander D. , Byrne Bernadette
Published: May 2021

Integral membrane transporters play essential roles in the movement of substrates across biological membranes. One approach to produce transporters suitable for structural studies is to introduce mutations that reduce conformational flexibility and increase stability. However, it can be difficult to predict which mutations will result in a more stable protein. Previously, we stabilised the uric acid‐xanthine transporter, UapA, a member of the SLC23 family, through introduction of a single‐point mutation, G411V, trapping the protein in the inward‐facing conformation. Here, we attempted to stabilise the structurally related BOR1 transporter from Arabidopsis thaliana, a member of the SLC4 family, by introducing the equivalent substitution. We identified possible residues, P362 and M363, in AtBOR1, likely to be equivalent to the G411 of UapA, and generated four mutants, P362V or L and M363F or Y. Stability analysis using heated Fluorescent Size Exclusion Chromatography indicated that the M363F/Y mutants were more stable than the WT AtBOR1 and P362V/L mutants. Furthermore, functional complementation analysis revealed that the M363F/Y mutants exhibited reduced transport activity compared to the P362V/L and WT proteins. Purification and crystallisation of the M363F/Y proteins yielded crystals that diffracted better than WT (5.5 vs 7 Å). We hypothesise that the increased bulk of the F and Y substitutions limits the ability of the protein to undergo the conformational rearrangements associated with transport. These proteins represent a basis for future studies on AtBOR1.