bluuebunny/crossref_metadata_2025 huggingface dataset:
FAALİYET TABANLI MALİYET SİSTEMİ VE LOJİSTİK SEKTÖRÜNDE BİR UYGULAMA
Authors: AKPINAR Aynur , ÖDEMİŞ Ali
Published: March 2021

Üretim ve maliyet kavramları birçok kavram gibi küreselleşme ile birlikte değişmiştir. Teknolojinin gelişmesiyle birlikte üretim sistemleri de gelişerek teknoloji yoğun bir hal almıştır. Üretim sistemlerinde görülen bu değişim ürün maliyetlerinin hesaplanması yöntemlerinde de değişiklikler getirmiştir. Çıkış noktası endirekt maliyetlerin dağıtımı ile ilgili sorunlara çözüm bulmak olan Faaliyet Tabanlı Maliyet (FTM) sistemi özellikle teknoloji yoğun üretimlerde ve rekabetin yüksek olduğu dönemlerde kullanılmaya başlayan maliyet hesaplama yöntemlerinden biridir.
Bu çalışmada lojistik sektöründe faaliyet gösteren bir işletmenin FTM sistemi kullanılarak birim maliyetleri hesaplanmıştır. Çalışma, farklı bir maliyet yaklaşımı olarak geliştirilen FTM sisteminin lojistik hizmeti sağlayan işletmelere uygun maliyetleme yöntemi olduğuna da örnek teşkil etmektedir.
ANAK SEBAGAI PELAKU TERORISME DALAM PERSPEKTIF EKOLOGI SOSIAL
Authors:   Pusat Penelitian dan Pengembangan Kesejahteraan Sosial, Kementerian Sosial RI, Setiawan Hari Harjanto , Wardianti Adhani ,   Balai Pemasyarakatan Kelas I Bandung, Kementerian Hukum dan HAM Republik Indonesia, Yusuf Iyus , Azikin Andi
Published: March 2021

Kejahatan terorisme dipandang sebagai pelanggaran terhadap hak asasi manusia, karena seringkali korbannya adalah masyarakat yang tidak berdosa. Fenomena baru yang muncul sebagai tindak kriminal di Indonesia adalah anak-anak yang dijadikan kader oleh para teroris. Penanganan anak yang terlibat dalam tindak pidana terorisme maupun anak dalam jaringan terorisme harus mendapat perhatian yang serius baik pemerintah maupun masyarakat. Tulisan ini akan menjawab dua permasalahan penting yaitu bagaimana posisi anak sebagai pelaku terorisme dalam perspektif ekologi sosial dan bagaimana implikasi kebijakan penanganan anak sebagai pelaku terorisme. Hasil kajian menunjukan bahwa lingkungan sosial yang mempengaruhi anak antara lain; lingkungan keluarga, kelompok sebaya, masyarakat dan peran media dalam membentuk menjadi seorang teroris. Sehingga anak sebagai pelaku teroris bukan hanya permasalahan hukum semata, namun permasalahan lingkungan yang membentuk perkembangan anak juga harus diselesaikan. Pandangan ekologi sosial cenderung memandang anak sebagai pelaku teroris merupakan korban dari lingkungan sosial yang membentuknya. Ketidaknyamanan di keluarga, penolakan masyarakat, ajakan teman sebaya dan pengaruh media yang dikendalikan teroris merupakan penyebab anak ikut dalam jaringan terorisme. Cara pandang ini akan berimplikasi pada kebijakan yang akan diambil dalam menyelesaikan permasalahan ini. Tulisan ini merekomendasikan bahwa anak seperti ini tidak boleh dipidana penjara, melainkan harus memperoleh program perlindungan khusus berupa deradikalisasi melalui reedukasi, konseling, rehabilitasi sosial dan pendampingan sosial.
Innovative pedagogical technologies in the enrichment of the 4th year of life children’s vocabulary in the process of physical education
Authors: Sakharova Olena
Published: March 2021

The article reveals the importance of innovative pedagogical technologies and their implementation in the process of young preschoolers’ physical education; the views of both teachers of the past and modern scientists on the use of innovative methods of working with children have been analyzed. Attention is paid to the role of interactive techniques and innovative technologies in preschool education, their impact on the preschool children’s mental development and the enrichment of the younger preschoolers’ vocabulary in the process of physical education. The author has defined the essence of such concepts as «innovation», «technology», «pedagogical technology», «innovative pedagogical technology», and «innovative activity». The article reveals scientists’ different views on the concept of «pedagogical technology»; three groups of creative teachers engaged in the innovative activity have been defined. Innovative methods and techniques of applying interactive learning elements, which were used in a pedagogical experiment to enrich children's vocabulary in the process of physical education in the preschool institution educational process, have been stated. An example of the younger preschoolers’ vocabulary enrichment in the process of awakening gymnastics, which series are conducted in a playful way and accompanied by poems, has been given. The method of fairy tale therapy, due to which the educator will help the child to overcome fear, learn to jump over a cord and activate the child's vocabulary with such words as «jump», «rope», «both legs», «half-bent knees», «stick», «fear», «witchcraft», etc., has been offered. The solution of vocabulary tasks
with younger preschoolers can be seen with the help of acupressure, which will enrich, activate and consolidate new and familiar words in children's vocabulary, and with the help of Fitball gymnastics, which is done while working both individually with children and in sports activities, children’s independent motor activity.
COVID-19 Australia: Epidemiology Report 36: Reporting period ending 28 February 2021
Authors:   COVID-19 National Incident Room Surveillance Team
Published: March 2021

This is the thirty-sixth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEDT] 28 February 2021. It includes data on COVID-19 cases diagnosed in Australia and the international situation.
Konsep Pendidikan Agama pada Zaman Milenial
Authors: Sulthani Dinil Abrar
Published: March 2021

This article was written to explain the concept of religious education in the millennial era. The young generations who are in the millennial era experience various life dilemmas. The potential of the younger generation must be directed in order to understand the substance of their responsibilities. This thought article aims to provide an overview of the importance of reminding each other and synergizing with the younger generation. The older generation took the role to leave the next generation strong, strong in science, religious understanding, and skills innovation. Thought writing is described using the literature method with a qualitative descriptive analysis approach. The results of the study show that 1) The younger generation has the opportunity to become superior individuals, 2) The younger generation can maintain the existence of religion in society, 3) The support of the older generation is very important in controlling the activities of the next generation. The conclusion is that there are three educational concepts that can be realized; 1) Learn more diligently, 2) Practice actualizing knowledge, and 3) Useful for many things.
Development of sub-product from the waste from bacaba processing (oenocarpus bacaba Mart) as a source of value aggregation and income generation
Authors: Mineli Michelle Marinho dos Santos , Martins Glêndara Aparecida de Souza , Pires Caroline Roberta Freitas , Ferreira Eskálath Morganna Silva , Oliveira Maria Olivia dos Santos , Silva Juliana Fonseca Moreira da
Published: March 2021

The integral use of fruits in the elaboration of new products is a clean and viable technological alternative. This type of utilization is necessary to allow the fruit considered seasonal to be available to the consumer throughout the year, adding value and generating income for the communities that produce them. The aim of this study was to use the residue of bacaba processing in the elaboration of a jelly, contemplating the whole cycle of information necessary for this product to be in the market, focusing on income generation for the producers of this fruit. The composition of the raw material used for processing was initially determined. After that, the jelly formulations were developed and the best formulation was stored for the determination of its shelf life and analysis of its production viability. It was possible to obtain a jelly formulation that will promote the valuation of a by-product that would be discarded generating a market alternative for small and medium producers.
Opinião de gestores sobre trabalhadores mais velhos no contexto organizacional
Authors: Pires Thais da Silva , Silva Luiz Fernando da , Rossaneis Mariana Angela , Haddad Maria do Carmmo Fernandez , Figueira Desirée Ariane Modos , Costa Raquel Gvozd
Published: March 2021

Objetivo: Identificar a opinião de gestores sobre trabalhadores mais velhos no contexto organizacional. Método: Estudo transversal, de abordagem quantitativa, realizado com 176 gestores de uma instituição pública. Os dados foram analisados por estatística descritiva, razão de prevalência, intervalo de confiança e p-valor. Resultados: Os gestores do sexo feminino consideraram o envelhecimento da força de trabalho como um problema (RP=0,872/IC=0,788-0,967/p=0,009). Os gestores mais velhos afirmaram que o aumento na média de idade do quadro de pessoal impactaria na imagem organizacional (RP= 0,888/ IC= 0,801-0,985/p= 0,024). Os jovens responderam que o impacto seria em absenteísmo (RP= 1,148/IC= 1,045-1,261/p= 0,004). As características favoráveis presentes nos trabalhadores, na visão dos gestores, são produtividade, habilidades sociais, confiabilidade e lealdade. Conclusão: Evidenciou-se percepções diversificadas e discordantes dos gestores sobre os trabalhadores mais velhos. Apesar de reconhecer as características positivas, os gestores ainda relacionam o envelhecimento a problemas, aumento de conflitos e alteração na base de conhecimento da instituição.
A percepção do enfermeiro sobre a sistematização da assistência de enfermagem ao recém-nascido prematuro na unidade de cuidados intensivos
Authors: Silva Gabrielle do Nascimento , Santos Graciele Lira dos , Silva Cleidiane de Jesus , Lima Fernando Conceição de , Ueno Thalyta Mariany Rêgo Lopes , Moura Letícia Diogo de Oliveira , Marcena Jaqueline Cardoso , Campos Fabíola Leonir Moreira , Oliveira Virgínea Mercês Lara Pessoa , Ferreira Milena Farah Damous Castanho , Fonseca Adrielly Cristiny Mendonça , Barral Diego Moraes , Ramalho Matheus Almeida
Published: March 2021

Objetivo: investigar a percepção do enfermeiro acerca da utilização da Sistematização da Assistência de Enfermagem no cuidado prestado ao recém-nascido prematuro, na Unidade de Cuidados Intermediários. Metodologia: Trata-se de uma pesquisa de campo, com abordagem qualitativa, de caráter descritivo, onde os dados foram obtidos por meio de uma entrevista semi-estruturada e um questionário próprio, composto de 05 perguntas abertas, realiza com 05 enfermeiras lotadas na UCI Neonatal de um hospital Público no Pará; utilizou-se a técnica de saturação para as respostas ao questionário e a análise do conteúdo fora baseado em Bardin. Resultado: quatro profissionais compuseram a amostra do estudo, sendo adultos jovens e do sexo feminino; a maioria possuía especialização na área, atuante por mais de dois anos, contratadas ou concursadas. Verificou-se que a assistência de enfermagem prestada é voltada para a realização dos procedimentos técnicos com utilização de protocolos; o conhecimento das enfermeiras em relação ao que é a Sistematização da Assistência de Enfermagem é condizente, porém demonstraram dificuldade em diferenciar de Processo de Enfermagem; barreiras institucionais e profissionais dificultam a aplicação da sistematização da assistência de enfermagem, porém são aplicadas nos cuidados voltados aos recém-nascidos prematuros. Considerações finais: o conhecimento e entendimento da temática em questão tem a trazer grandes benefícios, tanto ao profissional quanto ao recém-nascido prematuro, e demonstrar que os entraves do cotidiano da assistência de enfermagem, não podem ser maiores que a necessidade de oferecer uma assistência de qualidade.
Cuidados de enfermagem a idosas com transtornos mentais em uma instituição de longa permanência
Authors: Saldanha Viviane Segabinazzi , Beuter Margrid , Hildebrandt Leila Mariza , Leite Marinês Tambara , Nishijima Rafael Beuter , Backes Carolina , Oliveira Francine Feltrin de
Published: March 2021

O estudo teve como objetivo conhecer a vivência dos profissionais de enfermagem de uma instituição de longa permanência para idosos, no cuidado de idosas com transtornos mentais. Trata-se de uma pesquisa qualitativa, descritiva realizada em uma instituição de longa permanência, na região sul do Brasil. A coleta de dados ocorreu de novembro de 2016 a janeiro de 2017 por meio de entrevista semiestruturada com 20 profissionais de enfermagem. Os dados foram analisados de acordo com a proposta operativa de Minayo. Os resultados mostraram a dificuldade dos profissionais ao lidar com idosas com transtornos mentais. O comportamento agressivo das idosas repercutiu no medo dos profissionais em relação às agressões. Condições institucionais - falta de pessoal e sobrecarga de trabalho - foram relatadas como fatores deletérios ao cuidado às idosas com transtornos mentais. Conclui-se que há desconhecimento dos profissionais sobre os transtornos mentais quanto a suas abrangências e complicações. Salienta-se a importância de outros profissionais para suprir as necessidades das idosas.
Efficacy of dry needling in TMD treatment: clinical case report
Authors: Oliveira Andressa Silva de , Maia Italo Hudson Tavares , Rifane Tainah Oliveira , Silvestre Francisbênia Alves , Freitas Bárbara de Fátima Barboza de , Picanço Paulo Roberto Barroso , Feitosa Victor Pinheiro , Leitão Aline Kércia Adeodato
Published: March 2021

The purpose of this article is to report a clinical case of a patient with TMD, evaluating the efficacy of dry needling as a treatment. The study was carried out in a dental clinic of higher education, where the evaluation of the patient was performed in order to conclude a correct diagnosis complementing with the use of dry needling. Patient, female, 38 years old, reported pain throughout the muscular region of the face, where it was more pronounced in the parotid-massometric region, with spreading to the temporal region. After performing the evaluation in addition to the percussion and palpation tests, the patient was diagnosed with spreading myofascial pain, in addition to headache attributed to TMD bilaterally. As a therapeutic approach, the dry needling technique was performed, in addition to the orientation of Cognitive Behavioral Therapy, since the patient reported having parafunctional habits. The techniques used produced an effective improvement to the patient, where the patient reports a relief of the muscular pains when performing the dry needling.
Impacto da doença periodontal na qualidade de vida: uma revisão integrativa
Authors: Nascimento Júnior Mauro Bezerra do , Nóbrega Fernando José de Oliveira , Fernandes Eloísa Cesário , Andrade Micássio Fernandes de , Oliveira Camila Cristine Araújo de , Fernandes Filho Antônio Eliece , Santos Patrícia Bittencourt Dutra dos
Published: March 2021

Objetivo: Realizar uma revisão de literatura, com busca sistemática, observando as evidências quanto ao impacto da doença periodontal na qualidade de vida. Metodologia:  A pesquisa foi feita nas bases de dados Medline/Pubmed, SciELO, LILACS, Web of Science e Scopus, nas quais utilizou-se os descritores “Periodontal Diseases” e “Quality of Life”. Foram incluídos artigos publicados em português, inglês e espanhol que retrataram a temática no período compreendido entre 2015-2020. Excluiu-se os artigos duplicados e todos os estudos de revisão. Inicialmente, identificou-se 1435 artigos, restando 36 artigos após a observação dos critérios de elegibilidade. Resultados: A doença periodontal causa um impacto negativo na qualidade de vida relacionada à saúde oral, visto que, do total de artigos (n=36), trinta evidenciaram essa afirmativa, e quanto mais severa é a destruição periodontal, pior é a qualidade de vida (n=11). Entretanto, alguns estudos (n=4) não encontraram relações significativas entre a doença e a qualidade de vida ou obtiveram baixo impacto. Além disso, há resultados com alto impacto na qualidade de vida nos seguintes grupos: fumantes, ausência de seguro de saúde, obesos e diabéticos, grávidas, ansiosos, idosos, pacientes com doença renal terminal, cárie, hipertensão arterial. Conclusão: As doenças periodontais interferem negativamente na qualidade de vida das pessoas afetadas e há evidências de quanto maior a severidade da doença, maior é o seu impacto na qualidade de vida.  Contudo, são necessários estudos clínicos randomizados e estudos do tipo longitudinal para fortalecer esses achados.
Syphilis Diagnosis and Treatment: State of The Art
Authors: Trovato Emanuele , Tognetti Linda , Campoli Marco , Cinotti Elisa , Rubegni Pietro
Published: March 2021

The present review summarises the current knowledge in the field of syphilis diagnosis and treatment, along with epidemiologic and historical data. A literature search was conducted in PubMed and Google Scholar, using the search terms “syphilis”, “diagnosis”, “dermoscopy”, “management AND treatment”, “laboratory tests AND syphilis”, and “primary OR secondary OR tertiary OR congenital syphilis”. A total of 55 out of 100 papers were included in this review. An overview of the different clinical presentation of primary, secondary, tertiary, and congenital syphilis, with particular attention to dermatologic signs and dermoscopic examination, is provided. The panorama diagnostic procedures are illustrated, along with their accuracy and recommendation. Treatment and management options of patients at different syphilis stages are provided and discussed according to the referring guidelines. The dermatologist can play a key role in providing the early and correct diagnosis and setting up in the proper management of patients with syphilis infection.
Packaging Design: Communication with the Consumer
Authors:   Kharkiv State Academy of Design and Arts, Hanotska Olga
Published: March 2021

The article considers important issues related to brand positioning and product packaging design. Visual perception of this design product should solve a specific commercial task. Modern market is developing rapidly and packaging expands its functions and becomes multifunctional (ecological, interactive, exclusive). At the same time, buyers are becoming more demanding. Packaging design is a consistent process aimed at positioning the product, segmenting the target audience, identifying competitive advantages of the product, creating an exact design concept that provides individuality, creativity and attention to detail. The aim of the article is to consider the communication process in modern packaging design. Packaging design is one of the most important directions in visual communication design. Today we can conclude that packaging performs not only its original function (protection, storage and transportation of goods). Communication with a consumer is also an extremely important aspect, because it is the key point when choosing a packaging design strategy for a particular product group. It is extremely important to form an exact message and convey it to the target audience. Communicative function of packaging is also directly related to aesthetic perception and advertising of the product. Designers must be aware of the latest world trends because they are the ones who contribute to the introduction of the latest creative ideas in this area. All these innovations make it possible to fully reveal the key image of packaging design. New trends in the field of consumer packaging design put forward by the society and market have brought changes in functional features of packaging. Now much attention is paid to communication packaging, as packaging often appears the factor that stimulates the purchase of goods. It is able to promote brands and products depicted on it and to convey certain ideas about their properties.
The Altar Partition of the Okhtyrka Assumption Cathedral of 1738: The Stylistic Decision and Iconographic Program
Authors:   Kharkiv State Academy of Design and Arts, Shulika Viacheslav
Published: March 2021

The article is dedicated to the iconostasis of the Assumption Cathedral in Okhtyrka (1738). The iconostasis was installed at the expense of O. Lesevytsky (a colonel of Okhtyrka regiment and a brigadier of Sloboda regiments). The icons were painted by Kharkiv icon painter V. Dmitriev. While painting he was working in Kiev‑Pechersk Laura. The iconostasis of the Assumption Cathedral became an example of an innovative decision of altar partitions not only in Slobozhanshchyna, but also in the whole of Ukraine. The altar partitions reflected the stylistic innovations relevant for the first half of the 18th century – a combination of Rococo and Classicism. The iconostasis of 1738 demonstrates that the spread of these styles in Slobozhanshchyna took place much earlier than in Central and Western Ukraine, and the sacred art of Slobozhanshchyna regiments had its own path of development. The iconostasis of the Assumption Cathedral became the first altar partition, which broke with traditional for Ukraine and, in particular, for Slobozhanshchyna, stylistic and iconographic decisions of altar partitions. It can be considered the first altar partition, which opens a new era in the history of Ukrainian iconostasis. A new solution for iconostasis in Slobozhanshchyna was the introduction of the metric type in the construction of tiers (the rhythmic type was traditionally used before that), the elimination of the Deisus tier, which was replaced by a large-format Holiday tier. The iconostasis also shows internal influences. Thus, the Sovereign tier of the iconostasis presented images of Christ, the Birth‑Giver of God and saints, depicted in full length, which was widespread in Kyiv and had not previously been typical in Slobozhanshchyna (traditionally the Sovereign (bottom) tier of the iconostasis in Slobozhanshchyna consisted of half‑length images). A new solution of the Sovereign tier of the iconostasis was probably proposed by V. Dmitriev, who could transfer part of Kyiv icon-painting tradition to Slobozhanshchyna.
Literature Based Model as an Effort to Build Pedagogic Literacy Ability of Students Elementary School
Authors: Zakaria Zakaria , Mahfud Imam
Published: March 2021

The literacy learning paradigm must be able to direct students to understand the values ​​of pedagogic literacy. The government policy in the Regulation of the Minister of Education and Culture Number 23 of 2015 proclaims the school literacy movement or Gerakan Literasi Sekolah requiring students to read for 15 minutes as an effort to build a passion for reading, fostering imagination through reading activities with educational messages. Pedagogic literacy values ​​must be built from an early age in an effort to create students with character. One learning model that is considered capable of building students' pedagogic literacy skills is the literature based model. The artile aims to analyze the description of pedagogic literacy in elementary school learning and the didactic design of a literature-based model in building the pedagogic literacy skills of elementary school students. The researchers used the content analysis or  meta-analysis method. Sources of data in this study are journals and books related to literature-based models and pedagogic literacy. Then, the object of this research is the didactic design of the literature based model in building the pedagogic literacy skills of elementary school students. The result show that the literature-based model shows an increase in activity students including students' enthusiasm in following lessons, student interaction with teachers, student interaction with students, and student participation in concluding learning.

Keywords: Pedagogic Literacy Ability, Model Pedagogic Literacy, Students Literation
Action nounsvs.nouns as bases for denominal verbs in Czech: A case study on directionality in derivation
Authors: Ševčíková Magda
Published: March 2021

Suffixless action nouns are mostly analysed as deverbal derivatives (e.g., výběr ‘choice’ < vybírat ‘to choose.ipfv’), but dictionaries ascribe the reverse direction to some noun–verb pairs ( útok ‘attack’ > útočit ‘to attack.ipfv’) despite being both formally and semantically close to the former type. The question is addressed in the present study of whether any linguistic features can be identified in pairs of suffixless nouns and directly corresponding verbs that would speak in favour of one or the other direction. The analysis of 250 Czech suffixless nouns reveals a correlation between the number of directly related verbs derived by suffixes and the direction as recorded in the dictionaries: While deverbal nouns correspond mostly to a pair of verbs with different (aspect-changing) suffixes (cf. výběr ‘choice’ : vybrat/ vybírat ‘to choose.pfv/ipfv’), nouns that are bases for verbs tend to share the root with a single (imperfective) verb ( útok ‘attack’ : útočit ‘to attack.ipfv’). This correlation is elaborated into two different paradigms, one being based on verbal roots and the other on nominal roots, which might be applicable in hypothesizing the direction also with nouns that are not covered by the dictionaries.
SOX9 Knockdown-Mediated FOXO3 Downregulation Confers Neuroprotection Against Ischemic Brain Injury
Authors: Deng Yiming , Ma Gaoting , Gao Feng , Sun Xuan , Liu Lian , Mo Dapeng , Ma Ning , Song Ligang , Huo Xiaochuan , He Hongwei , Miao Zhongrong
Published: March 2021

Background

Evidence exists uncovering that SRY-box transcription factor 9 (SOX9) plays a role in ischemic brain injury (IBI). Thus, the current study was conducted to elucidate the specific role of SOX9 and the mechanism by which SOX9 influenced IBI.

Methods

The IBI-associated regulatory factors were searched by bioinformatics analysis. The rat model of IBI was generated using middle cerebral artery occlusion (MCAO) treatment. Neuronal cells were exposed to oxygen-glucose deprivation (OGD). The expressions of SOX9, forkhead box O3 (FOXO3), transcription of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), and IκB kinase α (IKKα) in OGD-treated neuronal cells were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. The interaction among CITED2, IKKα, and FOXO3 was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assays. Gain- and loss-of-function experiments were performed to verify the relationship among SOX9, FOXO3, CITED2, and IKKα and to investigate their functional effects on apoptosis and the inflammatory response of OGD-treated neuronal cells as well as neurological deficit and infarct area of the rat brain.

Results

SOX9, FOXO3, CITED2, and IKKα were highly expressed in OGD-treated neuronal cells. Silencing of SOX9 inhibited OGD-induced neuronal apoptosis and inflammatory response and reduced the neurological deficit and infarct area of the brain in the rats, which were caused by MCAO but were reversed by overexpressing FOXO3, CITED2, or IKKα.

Conclusion

Taken together, our study suggested that upregulation of SOX9 promoted IBI though upregulation of the FOXO3/CITED2/IKKα axis, highlighting a basic therapeutic consideration for IBI treatment.
Nujiangexanthone A Inhibits Hepatocellular Carcinoma Metastasis via Down Regulation of Cofilin 1
Authors: Zhang Li , Chai Zongtao , Kong Siyuan , Feng Jiling , Wu Man , Tan Jiaqi , Yuan Man , Chen Gan , Li Zhuo , Zhou Hua , Cheng Shuqun , Xu Hongxi
Published: March 2021

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor prognosis. High expression level of cofilin 1 (CFL1) has been found in many types of cancers. However, the role of CFL1 in HCC hasn’t been known clearly. Here, we found that CFL1 was up regulated in human HCC and significantly associated with both overall survival and disease-free survival in HCC patients. Nujiangexanthone A (NJXA), the caged xanthones, isolated from gamboge plants decreased the expression of CFL1, which also inhibited the migration, invasion and metastasis of HCC cells in vitro and in vivo. Down regulation of CFL1 inhibited aggressiveness of HCC cells, which mimicked the effect of NJXA. Mechanism study indicated that, knockdown of CFL1 or treatment with NJXA increased the level of F-actin and disturbed the balance between F-actin and G-actin. In conclusion, our findings reveal the role of CFL1 in HCC metastasis through the CFL1/F-actin axis, and suggest that CFL1 may be a potential prognostic marker and a new therapeutic target. NJXA can effectively inhibit the metastasis of HCC cells by down regulating the expression of CFL1, which indicates the potential of NJXA for preventing metastasis in HCC.
Testing Messages on Facebook to Promote Use of an HPV Educational Web-Intervention
Authors: Reno Jenna E. , Dempsey Amanda F.
Published: March 2021

In the US, the human papillomavirus (HPV) vaccine remains underutilized leading to disparities in HPV-related diseases. Latinx have some of the highest rates of cancer caused by HPV. In a previous study, we developed a tailored-messaging based online educational intervention (CHICOS) that was found to increase HPV vaccination intention among Latinx participants. The current research uses Facebook Advertising to test the comparative effectiveness of messages designed using the Extended Parallel Processing Model (EPPM) to promote the use of CHICOS among Latinx young adults and parents of adolescents. We also looked at differences in the effectiveness of messages that highlighted HPV-related cancers, genital warts, or a control condition as well as differences in Spanish vs. English messages. Results found Latinx young adults and parents, were more likely to click on Facebook Advertisements containing messages in Spanish and those that mention cancer risks pertinent to this population compared to those in English or messages that discuss genital warts. Thus, findings suggest that Facebook Advertising has the potential to be a useful tool for motivating information seeking online about HPV vaccination.
Opposite Trends in Holocene Speleothem Proxy Records From Two Neighboring Caves in Germany: A Multi-Proxy Evaluation
Authors: Weber Michael , Hinz Yvonne , Schöne Bernd R. , Jochum Klaus Peter , Hoffmann Dirk , Spötl Christoph , Riechelmann Dana F. C. , Scholz Denis
Published: March 2021

Holocene climate in Central Europe was characterized by variations on millennial to decadal time scales. Speleothems provide the opportunity to study such palaeoclimate variability using high temporal resolution proxy records, and offer precise age models by U-series dating. However, the significance of proxy records from an individual speleothem is still a matter of debate, and limited sample availability often hampers the possibility to reproduce proxy records or to resolve spatial climate patterns. Here we present a palaeoclimate record based on four stalagmites from the Hüttenbläserschachthöhle (HBSH), western Germany. Two specimens cover almost the entire Holocene, with a short hiatus in between. A third stalagmite grew between 6.1 ± 0.6 ka and 0.6 ± 0.1 ka and a fourth one covers 11.0 ± 0.4 ka to 8.2 ± 0.2 ka. Trace element and stable isotope data allow to compare coeval stalagmites and to reconstruct potential climate patterns in the Holocene. In addition, Sr isotopes reveal soil processes and recharge of the aquifer. The aim of this study was to evaluate the consistency of the proxy data recorded by the individual stalagmites and to validate the results using a multi-proxy approach. Due to the close proximity of HBSH (<1 km) to the intensively investigated Bunker Cave system, this dataset also provides the unique opportunity to compare this record with a time-series from another cave system in the same climate region. While the initial growth phase at the onset of the Holocene shows similar patterns in both caves, the data show an opposing trend in the past 6 ka, most likely induced by the effect of disequilibrium isotope fractionation, resulting in a strong increase in δ13C and δ18O values. The stable isotope data from Bunker Cave do not show this pattern. Trace element data support the interpretation of the HBSH stable isotope data, highlighting the importance of a multi-proxy approach, and the need to replicate speleothem records both within a cave system and ideally using other caves in the region.
Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists
Authors: Tang Hao , Cheng Yijun , Huang Jinyan , Li Jianfeng , Zhang Benyan , Wu Zhe Bao
Published: March 2021

Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.
A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors
Authors: Miranda-Lora América Liliana , Vilchis-Gil Jenny , Juárez-Comboni Daniel B. , Cruz Miguel , Klünder-Klünder Miguel
Published: March 2021

Background

Type 2 diabetes (T2D) is a multifactorial disease caused by a complex interplay between environmental risk factors and genetic predisposition. To date, a total of 10 single nucleotide polymorphism (SNPs) have been associated with pediatric-onset T2D in Mexicans, with a small individual effect size. A genetic risk score (GRS) that combines these SNPs could serve as a predictor of the risk for pediatric-onset T2D.

Objective

To assess the clinical utility of a GRS that combines 10 SNPs to improve risk prediction of pediatric-onset T2D in Mexicans.

Methods

This case-control study included 97 individuals with pediatric-onset T2D and 84 controls below 18 years old without T2D. Information regarding family history of T2D, demographics, perinatal risk factors, anthropometric measurements, biochemical variables, lifestyle, and fitness scores were then obtained. Moreover, 10 single nucleotide polymorphisms (SNPs) previously associated with pediatric-onset T2D in Mexicans were genotyped. The GRS was calculated by summing the 10 risk alleles. Pediatric-onset T2D risk variance was assessed using multivariable logistic regression models and the area under the receiver operating characteristic curve (AUC).

Results

The body mass index Z-score (Z-BMI) [odds ratio (OR) = 1.7; p = 0.009] and maternal history of T2D (OR = 7.1; p < 0.001) were found to be independently associated with pediatric-onset T2D. No association with other clinical risk factors was observed. The GRS also showed a significant association with pediatric-onset T2D (OR = 1.3 per risk allele; p = 0.006). The GRS, clinical risk factors, and GRS plus clinical risk factors had an AUC of 0.66 (95% CI 0.56–0.75), 0.72 (95% CI 0.62–0.81), and 0.78 (95% CI 0.70–0.87), respectively (p < 0.01).

Conclusion

The GRS based on 10 SNPs was associated with pediatric-onset T2D in Mexicans and improved its prediction with modest significance. However, clinical factors, such the Z-BMI and family history of T2D, continue to have the highest predictive utility in this population.
Regional Differences in Spatiotemporal Drought Characteristics in Great Britain
Authors: Tanguy Maliko , Haslinger Klaus , Svensson Cecilia , Parry Simon , Barker Lucy J. , Hannaford Jamie , Prudhomme Christel
Published: March 2021

Despite being one of the most damaging natural hazards, droughts and their spatiotemporal dynamics are typically not well understood. Great Britain, which is the focus of this work, has experienced many major drought episodes in the past, causing a range of socioeconomic and environmental impacts. Here, we apply a recently developed technique to identify and characterise past droughts, using space-time connectivity to extract events from a monthly gridded precipitation dataset covering 1862–2015, without imposing fixed geographical boundaries or time-frames. For each grid cell, the data was aggregated into four new time series using moving averages over 3-, 6-, 12- and 24-month windows. These reflect a range of response times for different types of drought impacts. Drought events were then extracted for each time window separately. In order to assess regional differences in drought characteristics, each extracted drought was assigned to one of three regions: the South-East (SE), the North-West (NW) and a “Transition” region in-between them. A frequency analysis of drought characteristics (duration, area, intensity and severity) highlighted differences between regions: for short and medium accumulation periods (3, 6, and 12 months), short and less severe droughts are more frequent in the NW than in the SE, whereas long, spatially extended and more severe droughts are more frequent in the SE than in the NW. However, for long accumulation periods (24 months), fewer differences are observed between the NW and the SE. In the “Transition” region, severe droughts are less frequent than in the other two regions. A timeline of historic drought events detected by our method included the vast majority of known drought events from previous studies, with a few additional ones, and we shed important new light on the relative severity of these historical drought episodes. Finally, an analysis of the spatial coherence between regions showed that the most extreme drought events presented little spatial coherence, whereas less severe droughts tend to be more spatially coherent. This has important implications for water resources planning and drought management strategies, particularly given the increasing emphasis on inter-regional water transfers as a potential solution in situations of extreme drought.
Three Histories of Greening and Whiteness in American Cities
Authors: Connolly James J. T. , Anguelovski Isabelle
Published: March 2021

How has urban greening related to the degree of whiteness in neighborhoods? The answer to this question provides an essential “historical diagnostic” that can be used to develop an approach to urban ecology which integrates racial and ethnic change into the planning for proposed interventions. In this paper we employ state sequence analysis to analyze the historical trend of greening (including the implementation of new parks, greenways, community gardens, green recreation areas, and nature preserves) between 1975 and 2014 in a sample of nine cities in the United States relative to concentrations of white and non-white residents. We divide the nine cities into three common growth trajectories and separately examine the trends for each growth trajectory. We further illustrate these trends by mobilizing qualitative data from field work in selected neighborhoods to help explain the processes that generate certain key findings in the quantitative data. We find that the relationship between greening and race/ethnicity differs according to city-level growth trajectory. Cities with continuous high and rapid levels of growth in the postwar period have the strongest link between increased greening and whiter populations. Meanwhile, in cities that contracted or had a punctuated growth pattern, non-white areas had a uniformly low level of greening that occurred mostly in recent years. In all, we show how urban growth, greening, and whiteness are inextricably associated qualities of American cities. We argue that understanding this association is essential for development of a race-conscious model for enhancing urban ecosystems.
Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?
Authors: Kaur Ekjot , Agrawal Ritu , Sengupta Sagar
Published: March 2021

DNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases including cancer. BLM is a 3′−5′ ATP-dependent RecQ DNA helicase that is one of the most essential genome stabilizers involved in the regulation of DNA replication, recombination, and both homologous and non-homologous pathways of double-strand break repair. BLM structure and functions are known to be conserved across many species like yeast,Drosophila, mouse, and human. Genetic mutations in the BLM gene cause a rare, autosomal recessive disorder, Bloom syndrome (BS). BS is a monogenic disease characterized by genomic instability, premature aging, predisposition to cancer, immunodeficiency, and pulmonary diseases. Hence, these characteristics point toward BLM being a tumor suppressor. However, in addition to mutations,BLMgene undergoes various types of alterations including increase in the copy number, transcript, and protein levels in multiple types of cancers. These results, along with the fact that the lack of wild-type BLM in these cancers has been associated with increased sensitivity to chemotherapeutic drugs, indicate that BLM also has a pro-oncogenic function. While a plethora of studies have reported the effect ofBLMgene mutations in various model organisms, there is a dearth in the studies undertaken to investigate the effect of its oncogenic alterations. We propose to rationalize and integrate the dual functions of BLM both as a tumor suppressor and maybe as a proto-oncogene, and enlist the plausible mechanisms of its deregulation in cancers.
Association Between a Tri-allelic Polymorphism in the Estrogen Metabolism Oxidoreductase NRH:Quinone Oxidoreductase 2 Gene and Risk of Breast Cancer by Molecular Subtype
Authors: Zhou Jiao-Qun , Zhu Si-Yuan , He Ye , Yu Ke-Da
Published: March 2021

Background: We hypothesized that NRH:quinone oxidoreductase 2 (NQO2) is a candidate susceptibility gene for breast cancer because of its known enzymatic activity on estrogen-derived quinones. A tri-allelic polymorphism in the NQO2 gene might be associated with the risk of luminal-like breast cancer.

Methods: In this case-control study, 2,865 women were recruited, including 1,164 patients with pathologically confirmed breast cancer and 1,701 cancer-free controls. The tri-allelic genetic polymorphism (I-29, I-16, and D alleles) was genotyped by a polymerase chain reaction and restriction fragment length polymorphism (RFLP)-based assay. Because the I-16 allele frequency is rare (approximately 1.0%), individuals carrying the I-16 allele were excluded from the analysis. Breast cancer subtypes were classified according to ER, PR, HER2, and grade.

Results: In the association analysis of allele, an increased risk of breast cancer is associated with I-29 allele [82.5% in case group and 79.0% in the control group; odds ratio (OR), 1.25; 95% CI, 1.09–1.43, compared with D allele, p = 0.0015]. In the association analysis of genotype, the I-29-containing genotype was significantly correlated with breast cancer under a dominant model (adjusted OR, 1.31, 95% CI, 1.12–1.54, p = 0.001). Moreover, in the subtype analysis, there was a significant association of the I-29/D polymorphism with luminal-like breast cancer (adjusted OR, 1.54, 95% CI, 1.22–1.94, p = 0.001 for luminal-A disease; adjusted OR, 1.37, 95% CI, 1.06–1.76, p = 0.014 for luminal-B disease) but not with HER2-enriched or triple-negative subtypes.

Conclusion: The tri-allelic polymorphism in the NQO2 gene is associated with breast cancer risk, especially for the luminal-like subtype. Our findings provide a new piece of molecular epidemical evidence supporting the hypothesis that estrogen and its metabolites are carcinogens of luminal-like breast cancer. Further external validation studies are needed.
HIV-Infected Patients Developing Tuberculosis Disease Show Early Changes in the Immune Response to Novel Mycobacterium tuberculosis Antigens
Authors: Meier Noemi Rebecca , Battegay Manuel , Ottenhoff Tom H. M. , Furrer Hansjakob , Nemeth Johannes , Ritz Nicole
Published: March 2021

Background: In individuals living with HIV infection the development of tuberculosis (TB) is associated with rapid progression from asymptomatic TB infection to active TB disease. Sputum-based diagnostic tests for TB have low sensitivity in minimal and subclinical TB precluding early diagnosis. The immune response to novel Mycobacterium tuberculosis in-vivo expressed and latency associated antigens may help to measure the early stages of infection and disease progression and thereby improve early diagnosis of active TB disease.

Methods: Serial prospectively sampled cryopreserved lymphocytes from patients of the Swiss HIV Cohort Study developing TB disease (“cases”) and matched patients with no TB disease (“controls”) were stimulated with 10 novel Mycobacterium tuberculosis antigens. Cytokine concentrations were measured in cases and controls at four time points prior to diagnosis of TB: T1-T4 with T4 being the closest time point to diagnosis.

Results: 50 samples from nine cases and nine controls were included. Median CD4 cell count at T4 was 289/ul for the TB-group and 456/ul for the control group. Viral loads were suppressed in both groups. At T4 Rv2431c-induced and Rv3614/15c-induced interferon gamma-induced protein (IP)-10 responses and Rv2031c-induced and Rv2346/Rv2347c-induced tumor necrosis factor (TNF)-α responses were significantly higher in cases compared to controls (p < 0.004). At T3 - being up to 2 years prior to TB diagnosis - Rv2031c-induced TNF-α was significantly higher in cases compared to controls (p < 0.004). Area under the receiver operating characteristics (AUROC) curves resulted in an AUC > 0.92 for all four antigen-cytokine pairs.

Conclusion: The in vitro Mycobacterium tuberculosis-specific immune response in HIV-infected individuals that progress toward developing TB disease is different from those in HIV-infected individuals that do not progress to developing TB. These differences precede the clinical diagnosis of active TB up to 2 years, paving the way for the development of immune based diagnostics to predict TB disease at an early stage.