bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic approach to families bringing up disabled child
Authors: Jusienė Roma
Published: January 2019

Birth of a handicapped child is usually viewed as a common family crisis. Parents of a handicapped child are considered to deal with grief and adaptation to child's disability reactions, and chronic stress later on. Valuable insights considering the psychological problems of the families with handicapped child may be derived from the systems theory. The present article deals briefly with the main concepts of the family with disabled child as a system. Also several causes of dysfunctional family system are analysed.
Media reports on suicide in the major dailies of Lithuania in 1994 and 1996
Authors: Gailienė Danutė , Trofimova Jelena
Published: January 2019

The aim of the present study was to assess the effect of issuing guidelines for suicide reporting on the actual practice of reporting in three main dailies of Lithuania. In 1994 we conducted 12 months survey of suicide reporting in “Lietuvos rytas”, “Lietuvos aidas” and “Respublika”. In 1995 the results were presented in written guidelines for suicide reporting and in the seminars for journalists. Following this intervention, a second, identical evaluation of suicide reporting covering three major dailies was carried out during the year 1996. The main variables on form, content and style of the newspaper reports before and after the intervention were compared (588 reports). In 1996 1,7 times more publications on suicide were published. Positive and negative changes in the quality of reporting were found in the second period of analysis. It is possible that the results were affected not only by the action of suicidologists, but also by the political action of one of the deputies of Lithuanian Seimas, who declared the intention to burn himself. This aroused a rather hot reaction in the society and in the newspapers.
Barriers and Stigma Experienced by Gay Fathers and Their Children
Authors: Perrin Ellen C. , Hurley Sean M. , Mattern Kathryn , Flavin Lila , Pinderhughes Ellen E.
Published: January 2019

BACKGROUND:

Gay men have become fathers in the context of a heterosexual relationship, by adoption, by donating sperm to 1 or 2 lesbian women and subsequently sharing parenting responsibilities, and/or by engaging the services of a surrogate pregnancy carrier. Despite legal, medical, and social advances, gay fathers and their children continue to experience stigma and avoid situations because of fear of stigma. Increasing evidence reveals that stigma is associated with reduced well-being of children and adults, including psychiatric symptoms and suicidality.

METHODS:

Men throughout the United States who identified as gay and fathers completed an online survey. Dissemination of the survey was enhanced via a “snowball” method, yielding 732 complete responses from 47 states. The survey asked how the respondent had become a father, whether he had encountered barriers, and whether he and his child(ren) had experienced stigma in various social contexts.

RESULTS:

Gay men are increasingly becoming fathers via adoption and with assistance of an unrelated pregnancy carrier. Their pathways to fatherhood vary with socioeconomic class and the extent of legal protections in their state. Respondents reported barriers to becoming a father and stigma associated with fatherhood in multiple social contexts, most often in religious institutions. Fewer barriers and less stigma were experienced by fathers living in states with more legal protections.

CONCLUSIONS:

Despite growing acceptance of parenting by same-gender adults, barriers and stigma persist. States’ legal and social protections for lesbian and gay individuals and families appear to be effective in reducing experiences of stigma for gay fathers.
Noun phrase complement in Nigerian English
Authors: Akinlotan Mayowa
Published: January 2019

The present study investigates the structure of of-complement noun phrase in Nigerian English, comparing findings with those of British and Ghanaian varieties. Of-complement is high in frequency and is a typical complement that has structural tendencies for recursiveness and complexity. A review of literature explicating the structural simplification hypothesis (Gorlach, 1998) suggests that the structure of-complement (or any other type) has received very little attention. Perhaps such scanty works show the different arguments surrounding its syntactic and theoretical status in different grammatical descriptions. Unlike many previous NP frameworks, Huddleston & Pullum (2002, 2004) argued that complements are not only a syntactic element within the NP structure, but also that they are of equal obligatory syntactic status as a head noun within an NP. This framework, unlike many others, therefore conceptualizes the complement slot as an important part in the scheme of things for an NP structure viz-a-viz its complexity. Thus, a serious examination of NP complexity would consider the cooperation (relationship) between a complement and the other syntactic elements constituting the NP structure. This is one of many issues that the present study sheds light on. On the basis of variables representing syntactic function and text type, together with corpus analyses of NPs extracted from the Nigerian component of International Corpus of English (ICE), the structural behavior of of-complement in the lights of other internal elements constituting an NP structure, is clearly shown. It is found that a complement is less likely to co-occur with other all internal elements (20%). Also, it is shown that an of-complement is likely to co-occur with prenominal elements (30%). Furthermore, the paper shows that a structural type of of-complement representing h-complement (i.e. an NP structure consisting of a head noun + a complement, see Huddleston & Pullum, 2002, 2004, and Akinlotan & Housen, 2017) is more likely to occur (26%) as an independent NP structure than to co-occur with postnominal elements (24%). The structural simplification hypothesis is manifested in our corpus data, as it is found out that a complement is more likely to be simple-structured (54%) than complex-structured (46%). On the predictive strength of syntactic function and text type (Biber et al., 1999; Schilk & Schuab, 2016; Akinlotan, 2017), the study finds syntactic function a better predictor than text type.
“Teacher, I need to show you a foreigner I have been talking to on my cellphone!” Unveling students’ understanding about technology use for enhancing the speaking skill in English language
Authors: Rio Marlon Machado Oliveira
Published: January 2019

The oral skill has been lately studied by researchers in the English Language Teaching field (ELT), once it is considered one of the hardest ones to be improved (Bygate, 2009). Some solutions have been suggested within the ELT literature as to assist students on this skill’s improvement (Lucas, 2001). Additionally, technology has taken its valuable position in society today, circumscribing the scholastic and working environments. Entangling both topics (the speaking skill and digital technology), this article displays an initial1 research carried out with English learners worldwide, in which pupils could voice their opinions concerning the use of digital technologies in their English learning path alongside the impact of them in fostering pupils’ oral skill. Preliminary results show both negative and positive views regarding the use of technology and the oral skill’s improvement.
The additional language classroom: reflections, research and technology
Authors: Perna Cristina Becker Lopes , Antunes Aline Jéssica , Andrighetti Graziela Hoerbe
Published: January 2019

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Formação inicial do pedagogo que atua como coordenador pedagógico: análises e reflexões dos saberes profissionais
Authors: Tozetto Susana Soares , Kailer Priscila Gabriele da Luz
Published: January 2019

O presente artigo analisa os saberes da formação inicial do Pedagogo que atua como coordenador pedagógico na escola. O cotidiano desse profissional, imerso por acontecimentos imprevisíveis, mobiliza saberes a cada nova situação. Portanto, apresentamos como objetivo central discutir os saberes específicos do coordenador pedagógico. Os principais autores que sustentam as análises aqui propostas são Tardif (2002), Gauthier (1998), André e Vieira (2007) e Gimeno Sacristán (1999). Assim, foi feito uma análise documental do Projeto Político Pedagógico do curso de Pedagogia da Universidade Estadual de Ponta Grossa-PR entre os anos de 2007 a 2010 e entrevistas com seis egressos do curso que atuam na escola pública municipal como coordenador pedagógico. Os resultados mostram que a amplitude dos saberes do coordenador pedagógico desafia as possibilidades de formar um profissional para diversas funções, como docente, gestor e pesquisador.
Narrativas digitais para uma aprendizagem significativa no Ensino Superior: qual a percepção dos estudantes?
Authors: Do Nascimento Ernandes Rodrigues , Dos Anjos Fábio Leandro Melo Ramos , Menezes Karla Karina Oliveira , De Oliveira Gregório Batista Lima
Published: January 2019

Nos últimos anos, buscando desenvolver uma educação que atenda a demanda atual do mercado profissional, muito tem se falado sobre metodologias ativas, ensino híbrido, inovação no ambiente educacional, entre outros temas que nos remetem ao processo de ensino e aprendizagem. Mas, na literatura, pouco se encontra sobre a percepção dos estudantes do ensino superior em relação ao uso das metodologias ativas no processo de ensinagem. O estudante desse nível de ensino, em sua maioria, trabalha em parte do dia, cuida da família em outro momento e estuda em determinado turno, possuindo dezenas de ocupações e escassez de tempo. Para ele, deve-se maximizar sua aprendizagem no menor tempo possível, mesclando atividades presenciais e virtuais, mas evitando deixar excesso de atribuições acadêmicas fora do ambiente escolar, pois o mesmo não dará a devida atenção. A partir disso, torna-se importante conhecer a sua percepção sobre o uso de metodologias ativas de ensino, objetivo deste artigo. O presente trabalho buscou conhecer a percepção dos estudantes de graduação da rede particular de ensino sobre o uso de narrativas digitais para uma aprendizagem significativa. A partir de uma abordagem qualitativa, a pesquisa foi desenvolvida por meio de entrevistas individuais, grupo focal, diário de campo e observação, durante a realização de um curso de extensão universitária. Os resultados demonstraram a percepção dos estudantes em relação ao uso das narrativas digitais como metodologias ativas, destacando pontos positivos e suas objeções no tocante ao processo de ensino e aprendizagem, despertando novas inquietações e sugerindo que outras pesquisas sejam realizadas.
A docência universitária e a experiência: o olhar sobre uma prática educativa desenvolvida pelo professor Jorge Larrosa
Authors: Alves Izandra , Burlamaque Fabiane Verardi
Published: January 2019

A experiência requer que aquele disposto a vivenciá-la esteja também propenso a abrir-se ao desconhecido e ao inusitado. É preciso correr riscos, pois ela é passional e, por isso, desencadeadora dos sentimentos e emoções os quais nem sempre dominamos. Possibilitar a vivência de experiências está cada vez mais difícil na atualidade visto que ela exige o silêncio, a parada, o olhar-se a fim de que algo aconteça naquele que a vive. Estamos quase sempre apressados e sem tempo para as experiências diárias que nos são oferecidas. Diante disso, pretendemos discutir nesse artigo a possibilidades de fazer da experiência uma prática educativa que possa ser adotada por educadores de distintas áreas e em diferentes níveis de educação. Para tanto, descrevemos uma atividade de leitura e discussão teórica acerca de alguns textos que compõem o corpus da disciplina ministrada pelo professor pesquisador Jorge Larrosa Bondia, da Universitat de Barcelona, com alunos do curso de Pedagogia Social dessa mesma universidade. A partir da prática proposta por Larrosa procuramos discutir conceitos acerca da leitura e da experiência como possibilidades para que o aluno leitor universitário seja tocado e movido ao seu interior por meio do texto e, assim, realmente possa, a partir dele, construir conhecimento, formar ou/e transformar-se, sendo, então, o agente de sua prática educativa.
Hibridismo tecnológico no cotidiano da sala de aula: analisando potencialidades e limites das tecnologias
Authors: Noronha Fabrícia Py Tortelli , Backes Luciana , Casagrande Cledes Antonio
Published: January 2019

O presente artigo explora o conceito de hibridismo tecnológico no cotidiano da sala de aula mediante potencialidades e limites das tecnologias analógicas (caneta e papel) e digitais (VisuAlg, Scratch e Kit Lego), no âmbito da dissertação intitulada A construção do conhecimento de algoritmos no contexto do hibridismo tecnológico: análise da prática pedagógica aplicada no IFRS, realizada no programa de Pós-Graduação em Educação, na linha de pesquisa “Culturas, Linguagens e Tecnologias na Educação”. O estudo caracterizou-se como sendo do tipo estudo de caso e tem como fundamentação teórica os pressupostos da epistemologia genética de Jean Piaget. Os dados coletados foram submetidos à Técnica de Análise de Conteúdo de Bardin (2006). Para a coleta dos dados empíricos, foram apresentadas tecnologias analógicas e digitais, as quais serviram de base tecnológica para o desenvolvimento dos processos de ensino e de aprendizagem de algoritmos na disciplina de “Lógica de Programação”. O contexto do hibridismo tecnológico potencializou a construção do conhecimento de algoritmos, sobretudo pela pluralidade de representação do conhecimento, contemplando variadas estratégias e linguagens para a aprendizagem, oportunizando o protagonismo no sujeito e atribuindo significado ao conhecimento.
Compartilhando experiências em sala de aula à luz do engajamento e da liderança estudantil: um estudo do autorreconhecimento dos acadêmicos do curso de Hotelaria da UFPE, Brasil
Authors: Belchior Maria Helena C. da Silva , Da Silva Ana Rosa Cavalcanti , Padilha Maria Auxliadora Soares
Published: January 2019

Os relatos desse estudo são centrados numa reflexão a partir de propostas educativas envoltas à uma dinâmica em que o engajamento do estudante aproxime o acadêmico do seu aprendizado, tendo o docente como partícipe mediador da ação. Tem como objetivo central avaliar o autorreconhecimento dos alunos da disciplina de Gestão do Lazer e da Recreação nas Empresas de Hospitalidade, no curso de Bacharelado em Hotelaria, da Universidade Federal de Pernambuco, a partir de uma prática educativa proposta à luz das relações existentes entre o engajamento estudantil e a liderança. Quanto aos procedimentos metodológicos optou-se pela abordagem quantitativa utilizando-se de um survey contendo 12 questões estruturadas a partir da Escala de Likert de cinco pontos. A amostra, do tipo não probabilística, foi definida por conveniência e composta por todos os discentes (19) que cursaram o componente curricular fruto de investigação. A aplicação dos formulários ocorreu em maio e junho de 2018 e análise dos dados em julho do corrente ano. Para a análise dos resultados foi utilizado o programa Microsoft Excel. A partir dos resultados avaliados é possível afirmar o êxito da atividade acadêmica proposta na disciplina promovida de maneira coletiva e discutida entre os sujeitos docente e discentes, a experiência de um trabalho construído a várias mãos. Ademais a necessidade de ampliação de propostas acadêmicas mais aproximadas à realidade do futuro profissional traz consigo a possiblidade de, ainda em sala de aula, se estudar, numa perspectiva mais aprofundada, cenários reais e possíveis de serem experenciados.
Relação dos pareceristas ad hoc do v. 9, n. 1-2, 2018
Authors: Dos Santos Pricila Kohls
Published: January 2019

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PERUBAHAN KONDISI DANAU LIMBOTO YANG TERDETEKSI DENGAN TEKNOLOGI PENGINDERAAN JAUH
Authors: Julzarika Atriyon , Dewi Esthi Kurnia
Published: January 2019

Saat ini data penginderaan jauh sudah mengalami perkembangan yang pesat, baik dalam aspek sensor, wahana, maupun spesifikasi resolusinya. Data penginderaan jauh dapat digunakan untuk mengidentifikasi sumber daya alam dan lingkungan. Penelitian ini bertujuan untuk mengidentifikasi perubahan kondisi Danau Limboto yang Terdeteksi dengan Teknologi Penginderaan Jauh.   Sumber daya perairan danau ini berupa kualitas air, luas permukaan, dan vegetasi air. Data yang digunakan adalah Landsat. Data tersebut digunakan untuk mengetahui perubahan danau secara visual serta perhitungan kualitas air, luas permukaan, dan vegetasi air (hidrofit)nya. Pada penelitian ini, kualitas air hanya difokuskan pada parameter TSS dan kecerahan. Kedua parameter ini bisa diekstraksi dengan metode e-SMART. Metode ini menggunakan band inframerah dekat pada citra Landsat. Hasil yang diperoleh adalah informasi spasial kualitas air, luas permukaan danau, dan vegetasi air di danau Limboto. Hasil ekstraksi kualitas air ini dilakukan uji dengan data lapangan. Uji akurasi menggunakan metode geostatistik non parameter (uji Fischer). Hasil uji akurasi yang diperoleh adalah95 % pada tingkat kepercayaan 1,96 σ. Uji akurasi dilakukan dengan membanding hasil pengukuran di citra dengan data lapangan.  Hasil penelitian ini diharapkan bisa digunakan juga untuk membantu kegiatan nasional serupa, yaitu pemantauan 15 danau prioritas di Indonesia.
KONDISI PADANG LAMUN DI PERAIRAN TIMUR INDONESIA (THE CONDITION OF SEAGRASS MEADOW IN THE WATERS OF EASTERN INDONESIA)
Authors: Supriyadi Indarto Happy
Published: January 2019

ABSTRAKPadang lamun memiliki peran penting dalam suatu ekosistem perairan dangkal (mangrove, lamun dan terumbu karang). Namun kegiatan pembangunan di wilayah pesisir yang terus meningkat telah mengakibatkan kerusakan padang lamun yang hampir terjadi di seluruh perairan Indonesia. Saat ini informasi terkait dengan keanekaragaman spesies, kondisi lamun, dan luasannya khususnya di perairan timur Indonesia masih kurang. Tujuan penelitian ini yaitu memberikan informasi keanekaragaman spesies, kondisi padang lamun dan luasannya. Metode yang digunakan yaitu mengumpulkan data primer hasil kajian sejak 2005-2016 serta data sekunder dari beberapa sumber data hasil pemantauan kesehatan terumbu karang dan ekosistem terkait (lamun) pada program pemulihan dan pengelolaan terumbu karang (Coremap)-CTI 2015-2016. Identifikasi spesies lamun berdasarkan pada McKenzie (2003), pengambilan data dan analisa kondisi lamun mengacu pada buku panduan pemantauan padang lamun dan berdasarkan KMNLH (2004) no. 200. Hasil identifikasi spesies lamun ditemukan 10 dari 12 spesies lamun yang ada di perairan Indonesia. Kondisi padang lamun di perairan timur Indonesia dikategorikan‘baik’ (43%),’sedang’ (50%) dan ‘jelek’ (7 %) dengan luas padang lamun saat ini yaitu 146.283,68 ha.                                                    ABSTRACTSeagrass meadows has an important role at the shallow waters ecosystems (mangrove, seagrass and Coral reef). Development activities in the coastal area which is on still the rise has resulted in damage of the seagrass meadow in Indonesia waters. Current information related to biodiversity of seagrass, condition and extent of area in the eastern waters of Indonesia is still lacking. The goal of the research is to provide information about biodiversity, condition of seagrass meadows and extent of seagrass. The methods used the primary data collection of the result of study since 2005-2016 and secondary data collection from the Reef Health Monitoring and related ecosystem (seagrass) activity in the Coral reef Management and Rehabilitation Programme (Coremap)-CTI 2015-2016. Seagrass identification based on McKenzie (2003), collection of data and analyze of seagrass condition refer to the guide book monitoring of seagrass and KMNLH (2004) no.200. The Results of the study is found 10 of the 12 species of seagrass have found in the Indonesia waters. The condition of seagrass meadows are generally 'good’ (43%), ‘medium’ (50%) and 'poor’ (7%). Extent of seagrass area currently is 146,283.68 ha.
Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities
Authors: Estrada Chelsea C. , Maldonado Alejandro , Mallipattu Sandeep K.
Published: January 2019

Inhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of this pathway. We also review the renal effects of VEGF inhibition’s mediation of key downstream signaling pathways, specifically MAPK/ERK1/2, endothelial nitric oxide synthase, and mammalian target of rapamycin (mTOR). Direct VEGFA inhibition via antibody binding or VEGF trap (a soluble decoy receptor) is associated with renal-specific thrombotic microangiopathy (TMA). Reports also indicate that tyrosine kinase inhibition of the VEGF receptors is preferentially associated with glomerulopathies such as minimal change disease and FSGS. Inhibition of the downstream pathway RAF/MAPK/ERK has largely been associated with tubulointerstitial injury. Inhibition of mTOR is most commonly associated with albuminuria and podocyte injury, but has also been linked to renal-specific TMA. In all, we review the experimentally validated mechanisms by which VEGFA-VEGFR2 inhibitors contribute to nephrotoxicity, as well as the wide range of clinical manifestations that have been reported with their use. We also highlight potential avenues for future research to elucidate mechanisms for minimizing nephrotoxicity while maintaining therapeutic efficacy.
Zn:CuO Heteroyapıların Yapısal, Optik, Fotolüminesans ve İletim Özellikleri
Authors: GÜNGÖR Elif
Published: January 2019

Bu
çalışmada, sol-jel yöntemi kullanılarak cam alt tabakalar üzerinde katkısız ve
Zn katkılı CuO (Zn:CuO ile belirtilmiştir) heteroyapılar büyütüldü. Çinko
konsantrasyonunun, ince filmlerin yapısal, optik ve elektriksel özellikleri
üzerindeki etkisi analiz edildi. Filmlerin kompozisyonu ve morfolojisini
araştırmak için X ışını kırınımı (XRD) analizi ve Alan-emisyon taramalı
elektron mikroskobu (FE-SEM) kullanıldı. Optik özellikler UV-Görünür bölge (UV-Vis)
ve Fotoluminesans (PL) spektroskopisi ölçümleriyle tanımlandı. Optik bant
aralığı enerjilerinin Zn katkılamasına bağlı olduğu bulundu. Sonuçlar, Zn
katkılamanın CuO filmlerin yapısal, elektriksel ve optik özelliklerini güçlü
bir şekilde etkilediğini gösterdi.
Neurostructural correlates of strength decrease following total knee arthroplasty: A systematic review of the literature with meta-analysis
Authors: Paravlic Armin H , Kovač Simon , Pisot Rado , Marusic Uros
Published: January 2019

Recent literature suggests that alterations in both neural and structural components of the neuromuscular system are major determinants of knee extensor muscle weakness after total knee arthroplasty (TKA). Therefore, the goal of this study was to investigate the maximal voluntary strength (MVS), voluntary muscle activation (VMA), and the cross-sectional area (CSA) of the muscle, up to 33 months after the TKA.  We searched relevant scientific databases and literature for outcomes of interest, including quadriceps MVS, VMA, and CSA. Ten studies met the inclusion criteria and involved a total of 289 patients. The quality of the studies was evaluated by Methodological Index for Non-Randomized Studies (MINORS). Results showed that quadriceps MVS markedly declines in the early postoperative period, after which it slowly and linearly recovers over time. However, the same phenomenon was not observed for VMA and CSA, which were not significantly altered after the TKA. Furthermore, a meta-regression analysis revealed that the change in VMA accounted for 39% of the relative change in quadriceps strength (R2=0.39; p=0.015) in the early postoperative period. Patients treated with TKA had considerable weakness of the quadriceps muscle, which was detectable up to 3 months after surgery. Although the change in VMA largely explains quadriceps weakness, this change and CSA differences were not significant, suggesting that other neural correlates, such as hamstrings coactivation, might alter quadriceps muscle function. Thus, more attention should be paid to address VMA failure and coactivation of antagonist muscles.  More comprehensive rehabilitation approaches may be required to target the whole neural circuit controlling the motor action.
Zebrafish (Danio rerio) Environmental Summary, Aquatic Resources Program, Boston Children's Hospital 2018 v3
Authors: Lawrence Christian , Best Jason , James Althea , Hurley Shane , Shia Mitchel , Urh Michelle
Published: January 2019

Environmental and housing conditions experienced by laboratory animals exert profound effects on their biology, physiology, and behavior. These parameters are important and often overlooked sources of potential variation in experiments, and should be reported in peer-reviewed publications in order to promote scientific reproducibility. To that end, here we provide a summary of the environmental conditionsin zebrafish (Danio rerio) aquaculture facilities at Boston Children's Hospital (BCH). We include data on the physico-chemical, health, and nutrition of zebrafish in three separate facilities at BCH: Karp, Enders SSB, and Enders Lobby*. In this year's version, we also include new information on our sanitization protocols and equipment. We also provide some additional characterization of our sampling methods for water parameters and health in a legend. This information will be applicable to any study involving zebrafish conducted in one of these three facilities during the year of 2018. *version amended to include new information on diet in this facility.
Hyperbranchedpolymer (HBP) preparations v1
Authors: Kim Il , Choi Changin
Published: January 2019

To start HPB development, a mechanical stirrer was installed in a three-necked flask, trimethylolpropane (an initiator) was added, and vacuum drying was performed at 60 °C for 4 h to remove any residual moisture. Potassium methoxide (a catalyst) was added at a mole number of 10% (catalytic efficiency) relative to the number of hydroxyl groups of the initiator. The mixture was then stirred for 30 min to attain the dehydrogenation reaction of the initiator. Vacuum drying was again performed at 60 °C for 30 min to remove the methanol generated as a by-product. Diglyme (about 0.8 times the volume of glycidol) was added, and the mixture was stirred for 15 min to disperse the ingredients. After raising the temperature to 100 °C, the glycidol (a co-monomer) was injected at a constant rate for 12 h using a syringe pump. After completion of the injection, the mixture was allowed to react for another 5 h to complete the reaction. Methanol was then added to remove any residual activity. The product was then dissolved to create a saturated solution and precipitated with excess acetone. The HBP was produced by repeating this process three times, at which point it had been purified. The purified HBP was then vacuum-dried at 80 °C for more than 12 h to remove residual methanol and acetone. This process was presented in Fig 1.
iDisco immunolabeling in brown adipose tissue (BAT) v1
Authors: Lee Seoeun , Zeltser Lori
Published: January 2019

This protocol describes how to stain Brown Adipose Tissue using iDisco protocol and visualize the result via confocal microscope.
Efficacy and safety of nivolumab in the treatment of relapsed/refractory classical Hodgkin’s lymphoma: Pavlov First Saint Petersburg State Medical University experience
Authors: Lepik K. V. , Mikhailova N. V. , Kondakova E. V. , Tsvetkova L. A. , Zalyalov Yu. R. , Borzenkova E. S. , Moiseev I. S. , Baykov V. V. , Afanasyev B. A.
Published: January 2019

Background . Using modern first-line chemotherapy more than 80 % of patients with classical Hodgkin’s lymphoma can be cured, however, in 15–20 % of cases there is a relapsed/refractory disease. The use of nivolumab in international clinical practice has significantly improved treatment results of patients with relapsed/refractory classical Hodgkin’s lymphoma.

Objective of this study is to evaluate the results of therapy with nivolumab in the сlinic of Pavlov First Saint Petersburg State Medical University.

Materials and methods . The retrospective analysis included treatment results of 101 patients with relapsed/refractory classical Hodgkin’s lymphoma who received nivolumab in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation from February 2016 to August 2018. The group included 90 patients who received nivolumab as part of an named patient program. Therapy response was assessed using CT/PET-CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety and tolerability were assessed by registering adverse events in accordance with NCI CTCAE version 4.03 criteria. Results . Median follow-up was 25 months. The response was registered in 64 % of patients: in 32 (31.6 %) – complete response and in 33 (32.7 %) – partial response. Stabilization and progression as the best response were registered in 5 (4.9 %) and 10 (9.8 %) patients, respectively. Indeterminate response was observed in 21 (20.6 %) patients. The 2-year overall survival was 96 %; the median of overall survival was not achieved. Progression-free survival (PFS) in studied patients was 40.6 %. The median of PFS was 17.9 months. There were no significant differences in PFS between patients with a partial and indeterminate response. Adverse events were reported in 87.1 % of patients. Severe adverse events (III–IV grade) occur in 18.8 % of patients.

Conclusion . The results of a retrospective study of nivolumab therapy in Russian patients with relapsed/refractory classical Hodgkin’s lymphoma are consistent with published international data. Nivolumab demonstrates high efficacy as a monotherapy for relapsed/refractory classical Hodgkin’s lymphoma, regardless of previous therapy type and duration with well tolerance. Pseudo-progression phenomena during immunotherapy require revision of the traditional Hodgkin’s lymphoma therapy response criteria.
Blood coagulation in venous thrombosis, complicating treatment of children, adolescents and young adults with lymphomas
Authors: Dmitriev V. V. , Fedorova A. S. , Lipay N. V. , Begun I. V. , Dunaev I. A. , Dmitriev E. V.
Published: January 2019

Objective of the study was to compare blood clotting parameters in lymphoma patients with or without venous thrombosis (VT), as well as to analyze the duration and outcome of anticoagulant therapy in children, adolescents and young adults with lymphoma, whose program treatment was complicated by VT.

Materials and methods . The analysis included 28 patients with lymphoma (Hodgkin lymphoma – 5, non-Hodgkin lymphoma – 23), aged from 2 to 25 years (median – 16.0 years), whose program treatment in 2005–2017 was complicated by VT. The case-control study was carried out to compare the parameters of blood coagulation. The control group consisted of 22 patients, aged from 2 to 20 years (median – 15.5 years) with the same diagnosis, age, therapy protocol and phase of treatment who had no thrombotic complications. The comparison group consisted of 35 healthy children aged from 3 to 18 years (median – 14.0 years).

Results . There was no difference in majority of blood clotting parameters in lymphoma patients with or without VT. Hyperfibrinogenemia and an increased D-dimers level distinguished patients with lymphoma, regardless of the presence or absence of thrombosis, from healthy children of the same age (р<0.05). Anticoagulant therapy up to 3 months received 10 patients, for 4–6 months – 4, for 7–12 months – 12, up to 18 months – 2. One adult patient with a homozygous mutation 20210G>A gene of the factor II takes warfarin continuously for a long time after relapse of VT. Complete recanalization of the thrombosed vessel occurred within the first 3 months in 9 patients, within 4–6 months – in 1, within 7–12 months ‒ in 4. Partial recanalization within 3–12 months was confirmed in 8 patients. Vein obliteration, mainly the internal jugular vein, as the outcome of VT occurred in 6 patients within 4–12 months.

Conclusion . Detection of routine blood clotting parameters does not allow identifying patients with thrombosis among children, adolescents and young adults with lymphoma. Fibrinogen and D-dimers levels were significantly higher in lymphoma patients, than in healthy children. Anticoagulant therapy for 3–12 months led to the complete or partial recanalization of VT in 79 % of patients. To detect blood clotting parameters by thrombosis development, as well as to reveal and monitor transient and permanent risk factors are necessary to specify the cause of VT and to determine the appropriate anticoagulant therapy.
Impact of malignant neoplasms on musculoskeletal system in children (literature review)
Authors: Tikhonova O. A. , Krutikova N. Yu. , Karelin A. F. , Zhukovskaya E. V. , Rumyantsev A. G.
Published: January 2019

Because of the successful implementation of modern treatment technologies at any stage of therapy of children with oncohematological diseases, their overall and disease-free survival has increased significantly. According to recent observations, 80 % of children after the completion of a special antitumor treatment continue to have changes of different organs. Almost all patients are at risk for late complications from the musculoskeletal system but little attention is paid to this issue. Evaluation of long-term complications from the musculoskeletal system and mineral metabolism in patients, development of their complex rehabilitation and prevention is an actual problem of pediatric oncology and hematology. This review summarizes data on long-term complications from the musculoskeletal system after special therapy. The necessity of diagnostics approaches harmonization and correction of not only the most common complications, but also little studied conditions, such as reduction of bone mineralization, is shown. It is noted that multidisciplinary rehabilitation treatment of children in remission can not only correct the consequences of the underlying disease, concomitant pathology and the consequences of special therapy but also reduce the disability of children.
Role of KIR typing in donor selection prior to allogeneic hematopoietic stem cell transplantation: literature review
Authors: Zakharova V. V.
Published: January 2019

Natural killer (NK) cells are the first population to recover after allogeneic hematopoietic stem cell transplantation. Since the report in 2002 by L. Rugerri et al. showing the effectiveness of NK cell alloreactivity in haploidentical stem cell transplantation, a lot of conflicting studies have appeared about the role of NK alloreactivity in haploidentical and matched unrelated donor transplantations. Current studies demonstrate that the beneficial effects of donor NK alloreactivity are dependent on the transplant protocol – conditioning regimen, graft processing procedure and graft-versus-host disease.
Study of myelodysplastic features in patients with myelodysplastic syndromes by multicolor flow cytometry
Authors: Davydova O. Yu. , Galtseva I. V. , Parovichnikova E. N. , Kokhno A. V. , Kapranov N. M. , Troitskaya V. V. , Mikhailova E. A. , Fidarova Z. T. , Moiseeva T. N. , Kuzmina L. A. , Lukina E. A. , Obukhova T. N. , Grebenyuk L. A. , Kovrigina A. M. , Dvirnyk V. N. , Savchenko V. G.
Published: January 2019

Background . Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases of the hematopoiesis system characterized by dismyelopoiesis and cytopenia, the presence of cytogenetic aberrations and a high risk of transformation into acute myeloid leukemias. Diagnosis of MDS requires a comprehensive approach and mandatory performance of cytological, cytochemical and cytogenetic studies of bone marrow aspirate, as well as histological examination of trephine biopsy. However, in some cases it is necessary to undergo a diagnostic test that would allow verification of the MDS. The study of bone marrow aspirate by multicolor flow cytometry (MFC) can be considered as an additional diagnostic criterion in the diagnosis of MDS.

The objective of the study was to estimate the incidence of myelodysplastic features in patients with various forms of MDS by the MFC method. 

Materials and methods . The study included 79 patients with MDS: 8 with MDS with 5q deletion, 33 with MDS without excess blast cells and 38 with excess of blasts. A bone marrow aspirate test was performed by 6-color flow cytometry. The control group included 35 donors of allogeneic bone marrow. The analysis resulted in a conclusion on the Ogata score scale, the Wells prognostic scale and the combined Ogata–Wells scale. When using the screening method, the presence of two or more cytometric signs of MDS was detected in 60 (75.9 %) of 79 MDS patients. Wells score was higher in MDS group with an excess of blast than in others. Using the combined Ogata–Wells scale, cytometric aberrations were found in 70 (88.6 %) of 79 MDS patients. In patients with MDS with an excess of blasts, the incidence of increased CD34+ and/or CD117+ myeloid cells was higher than in MDS patients without an excess of blasts and an MDS with a 5q deletion. The frequency of abnormal cytometric parameters (anomalous expression of CD34, CD117, CD56+ myeloblasts) in these groups did not differ. In patients with isolated 5q deletion and MDS without excess of blasts, an increased proportion of CD7+CD34+ cells was more often detected than in MDS with an excess of blasts.

Conclusion . Thus, cytometric abnormalities in MDS are common, even in patients without excess of blasts. The MFC method can be used as an additional diagnostic method in the initial diagnosis of MDS.
Clinical and biological features of acute myeloid leukemia with MLL gene rearrangements in children and results of therapy according to protocols AML-MM-2000/2006 in the Republic of Belarus
Authors: Barovskaya Yu. A. , Stegantseva M. V. , Aleinikova O. V.
Published: January 2019

Objective of the study . Analysis of the treatment outcomes of patients with MLL rearrangements in the Republic of Belarus within protocols AML-MM-2000 and AML-MM-2006.

Materials and methods . The study included 151 patients with newly diagnosed acute myeloid leukemia (AML) who were treated according to protocol AML-MM-2000 and AML-MM-2006. 11q23 abnormalities were detected in 40 (26.5 %) out of 151 patients.

Results . The performed analysis of the survival outcomes of patients with 11q23 depending on the protocol showed that the probability of 5-year event-free survival (EFS) was significantly better (p = 0.0110) in children receiving treatment under protocol AML-MM-2006 (86 ± 13 %) compared with that of the patients included in protocol AML-MM-2000 (23 ± 12 %). Using protocol AML-MM-2006 allowed reducing the cumulative incidence of relapse (CIR) in this cohort from 46.2 ± 15.1 to 14.3 ± 14.3 % (p = 0.1609). EFS probability in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) was 100 %, whereas in the group without alloHSCT – 31 ± 12 %, p = 0.0359. The treatment outcomes of patients with t(1;11) are comparable to those with CBF leukemia. The risk of relapse in patients with t(10;11) is higher than in the rest of the 11q23 cohort (62.5 ± 19.2 % versus 21.9 ± 7.5 %; p = 0.0136). CIR in patients with t(9;11) decreased from 42.8 % in protocol AML-MM-2000 to 15.4 % in protocol AML-MM-2006 (p = 0.1411).

Conclusion . For the described cohort of patients alloHSCT is the best option for post-remission therapy. The worst prognosis is determined in patients with t(10;11), whereas the presence of t(1;11) is a favorable prognostic factor. Using the arm with cladribine showed to be effective in patients with t(9;11). To obtain reliable outcomes, we consider it reasonable to continue the study with the use of cladribine in patients with t(9;11).
Flow cytometric analysis of leukemic blast cells in pediatric B-cell precursor acute lymphoblastic leukemia with translocation t(12;21)(p13;q22)/ETV6-RUNX1
Authors: Permikin Zh. V. , Popov A. M. , Verzhbitskaya T. Yu. , Riger Т. О. , Arakaev O. R. , Vlasova A. A. , Olshanskaya Yu. V. , Kazakova A. N. , Tsvirenko S. V. , Saveliev L. I. , Tsaur G. A. , Fechina L. G.
Published: January 2019

The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ETV6RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia patients.

Results . ETV6-RUNX1 fusion gene transcript was revealed in 118 (22.4 %) out of 526 children with B-cell precursor acute lymphoblastic leukemia. Leukemic blast cells in ETV6-RUNX1-positive patients more frequently had high CD10 expression, myeloid markers co-expression , including CD13, CD33, CD117, and absence of CD20 than in ETV6-RUNX1-negative ones. Nevertheless diagnostic test performance characteristics of each single parameter was not strong enough for predicting the presence of translocation t(12;21)(p13;q22)/ETV6-RUNX1.

Conclusion . Thus application of conventional set of immunological markers does not allow reliable distinguishing this patients’ subgroup. However antibodies panel enlargement, high degree of flow cytometry standardization and additional analytical methods can potentially improve applicability of antigen profile analysis for separation of patients with translocation t(12;21)(p13;q22)/ETV6-RUNX1.
The role of HPV16 regulatory region methylation in viral oncogenes E6 and E7 eхpression in primary cervical cancer lesions
Authors: Abramov P. M. , Katargin A. N. , Fedorova M. D. , Kisseljova N. P. , Pavlova L. S. , Vinokurova S. V.
Published: January 2019

Background.Overexpression of the human papillomavirus oncogenes E6 and E7 is a major factor in initiation and progression of HPV-induced tumors. Inactivation of negative regulatory function of E2 protein – the main viral transcription and replication regulator – is considered to be an important mechanism leading to the viral oncogenes overexpression. It is known that the loss of E2 functions occurs due to disruption of E2 open reading frame during the viral DNA integration into a cell genome in a part of HPV-positive tumors. An alternative mechanism of E2 function blocking in tumors retained its expression can be methylation of the HPV regulatory region, since it is known that E2 is incapable to bind its methylated binding sites.

The study objectiveis to analyze methylation of the HPV16 regulatory region and expression of the viral E6 and E7 oncogenes in E2 expressing or non-expressing clinical samples of cervical cancer.

Results.It has been demonstrated that the level of the HPV16 URR methylation in E2-expressing lesions is significantly higher than that in non-expressing cervical cancer lesions. Demethylation of the HPV16 promoter in cervical cell line Caski is followed by decrease of the viral E6 и E7 oncogenes mRNA levels, supporting the hypothesis that methylation is necessary for effective E6 and E7 transcription and indicates on restitution of E2 regulatory function in E2-expressing cervical cancer cells.

Conclusion.These data suggest that methylation of E2 binding sites in HPV16 regulatory region blocking E2 protein binding represents an important mechanism ensuring high level of the viral E6 and E7 oncogenes expression.
Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
Authors: Enikeev A. D. , Komelkov A. V. , Zborovskaya I. B. , Galetsky S. A. , Skryabin G. O. , Tchevkina E. M.
Published: January 2019

Background.The non-canonical activity of retinoic acid (RA) was discovered relatively recently and consists in the rapid activation of intracellular signaling pathways by the mechanisms not related to the transcriptional activity of the RA nuclear receptors. Separate data suggest that this activity can stimulate the processes of malignancy and contribute to the formation of tumor cell resistance to RA as a therapeutic agent. However, little is known about the mechanisms of this activity. It is also unclear how universal this effect is; does the RA-dependent activation of different signaling protein kinases occur in the same cells, and whether activation of these kinases is interrelated.

Materials and methods: cultivation of non-small cell lung cancer cells and neuroblastoma cells under standard conditions and with incubation with all-trans retinoic acid (ATRA); immunoblotting.

Results. Here we studied the effect of ATRA on the activation of Akt and Erk1/2 protein kinases depending on the incubation time. The analysis revealed RA-dependent activation of both kinases in all studied non-small cell lung cancer and neuroblastoma cell lines. Activation of Akt and Erk1/2 occurred at five minutes of incubation, which corresponds to the non-transcriptional (non-canonical) activity of the RA, however, further activation kinetics of the two kinases differed essentially.

Conclusion.We found that ATRA causes rapid activation of Erk1/2 and Akt protein kinases in both non-small cell lung cancer and neuroblastoma cells. The differences in the kinetics of RA-dependent stimulation of these two kinases suggest that their activation is mediated by independent mechanisms.
Tumor associated macrophages: current research and perspectives of clinical use
Authors: Gratchev A. N. , Samoilova D. V. , Rashidova M. A. , Petrenko A. A. , Kovaleva O. V.
Published: January 2019

Macrophages are the key cells of the innate immune system. One of the main functions of macrophages is the regulation of inflammation. Being common in all tissues and organs of the human body, tissue macrophages control their condition and guarantee a timely and effective response to damage, pathogen penetration or cell transformation. After eliminating the cause of inflammation, macrophages initiate the processes of healing and restoration of tissue homeostasis. At the end of the 20thcentury, the concept of macrophage activation dichotomy was proposed, which divided them into classically (M1) and alternatively (M2) activated ones. The development of this concept has led to the description of a wide variety of macrophage phenotypes. At the same time, M2 continues to be considered a prototype of tumor associated macrophages (TAM).

TAM represent one of the most important cell types in the tumor microenvironment. Like all macrophages, they have a certain level of heterogeneity and plasticity, which develop under the influence of cytokines and growth factors produced by tumor cells. TAM, in turn, produces growth factors, cytokines and extracellular matrix components that support the progression of the tumor and increase its malignant potential. Numerous clinical studies have shown that the amount of TAM is often correlated with a poor prognosis of the disease. TAM perform a large number of functions necessary to maintain tumor progression. They are capable of stimulating angiogenesis and reorganization of the vascular system. Since the role of TAM in tumor development has become apparent, various attempts have been made to use them in the clinic.  It can be confidently asserted that various TAM markers are very attractive as diagnostic and prognostic markers of various tumors, and also as promising targets for the development of new targeted therapeutic agents.