bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the Cultures of Romania and The Netherlands: When East Meets West
Authors: Van der Berg Peter
Published: November 2020

Romania, a former communist country and a recent member to the European Union, and TheNetherlands, one of the oldest EU members with a long history of democracy, were compared onnational and organizational culture variables. A total of 1,182 Dutch and Romanian participantscompleted questionnaires that measured (a) Hofstede’s four national culture dimensions ofpower distance, uncertainty avoidance, individualism, and masculinity, (b) what they perceivedcurrently in their jobs (actual practices) and what they wished for in an ideal job (values) on fivedimensions of organizational culture: autonomy, interdepartmental coordination, externalorientation, human resource orientation, and improvement orientation, and (c) practices andvalues for transformational leadership. The results showed that the Netherlands scored higher onindividualism, and lower on power distance and masculinity, than did Romania. The Dutchperceived higher levels of how autonomy, interdepartmental coordination, human resourceorientation, and improvement orientation is actually practiced in organizations, and lowerpractices levels for external orientation and transformational leadership than did the Romaniansample. With respect to values, the Dutch scored higher on autonomy and lower oninterdepartmental coordination, external orientation, human resource orientation, improvementorientation, and transformational leadership than did the Romanians. The finding that Romaniansare lower on most practices and higher on most values suggests that Romanians desire changeand that East and West European countries within the EU will grow closer to one another otherover time.
FEMINICÍDIO E VIOLÊNCIA DOMÉSTICA
Authors: De Souza Luciano Anderson , De Barros Paula
Published: November 2020

O artigo faz uma análise da Lei do Feminicídio, Lei nº 13.104/2015, que incluiu a qualificadora do feminicídio nos casos de homicídio praticado contra a mulher, por razões da condição de sexo feminino. Adotou-se uma abordagem crítica de viés político-criminal e dogmático penal, destacando avanços e retrocessos que poderão ocorrer com a lei. A análise é feita dentro do panorama sobre como a matéria de violência de gênero é tratada à nível internacional. É feito um paralelo com a legislação e políticas públicas de Portugal sobre violência doméstica e de gênero. A partir da análise comparativa entre as medidas tomadas pelos países, são feitas sugestões para a melhora do contexto brasileiro.
O REFORÇO AOS ESTIGMAS DE GÊNERO: MENINAS NO SISTEMA SOCIOEDUCATIVO BRASILEIRO
Authors: Norkevicius Douglas
Published: November 2020

O presente artigo observou a presença dos marcadores típicos da diferença de gênero que se apresentam em casos específicos do funcionamento da justiça juvenil. Através da identificação de figuras de gênero que são incentivadas na execução de medidas socioeducativas de internação, este trabalho analisou a localização das mesmas figuras em fases anteriores do processo de criminalização: o ato delitivo e sua relação com as sentenças que impõem as medidas às meninas que atravessam o sistema socioeducativo brasileiro. Dessa forma, buscou apresentar a relação paradoxal entre a penalização dessas figuras e sua imposição, quando na execução das medidas socioeducativas.
MULHERES ESTRANGEIRAS E CÁRCERE NO BRASIL: A DUPLA INVISIBILIDADE
Authors: De Proença Adriana
Published: November 2020

O presente artigo busca analisar as principais demandas e dificuldades das mulheres estrangeiras em situação de cárcere no Brasil, a fim de demonstrar a dupla penalização a que são submetidas. Pensar o sistema prisional brasileiro implica em pensar sobre questões de gênero, raça, nacionalidade, classe social, bem como em violência institucional. Para tanto, serão abordadas as condições em que se dá o cárcere feminino no país, com destaque aos percalços específicos das mulheres estrangeiras, tais como os referentes ao idioma, à distância de sua família, à regularização migratória, à maternidade, a questões processuais e ao procedimento de expulsão, à luz dos preceitos internacionais e nacionais de direitos humanos relacionados ao tema.
Tüketicilerin Bölge Orijinli Elma Tüketim Profilleri ve Piyasa Payları: TRA1 Bölgesi Örneği
Authors: Topcu Yavuz
Published: November 2020

Çalışmanın amacı, bölge orijinli Amasya, Isparta, Bayramiç ve yabancı orijinli elmaların tüketim tercihleri üzerinde etkili olan faktörler ve onların seviyelerine bağlı olarak mamul profillerinin tasarlanması ve her bir profilin piyasa payının belirlenmesidir. Çalışmanın ana materyali, TRA1 Bölgesi‘nde (Erzurum, Erzincan ve Bayburt) ikamet eden ve elma tüketen 600 hane halkı ile yüz yüze yapılan anketlerden temin edilen birincil verilerdir. Tüketicilerin toplam faydasını maksimum kılan elma profillerini tasarlamak ve her bir profilin piyasa payını belirlemek için Conjoint Analiz kullanılmıştır. Ayrıca, her bir ürün profili ve piyasa paylarını tüketici gelir düzeyine göre gruplandırmak için Kümeleme Analizi kullanılmıştır. Araştırma sonuçları; düşük gelirli tüketicilerin elma fiyatı (%41) ve büyüklüğüne (%32), fakat yüksek gelirli tüketicilerin bölge orijini (%62) ve renk (%13) faktörlerine büyük önem atfettiklerini ortaya koymuştur. Diğer taraftan, 2 numaralı elma profili hem düşük gelir grubu hem de bütün tüketici kitleleri için toplam faydayı maksimum kılarken; 17 numaralı profil ise yüksek gelir grubu için en yüksek memnuniyeti temin etmiştir. 2 ve 17 numaralı profillerde bölge orijinini temsil eden Amasya elmasının düşük ve yüksek gelir grupları için piyasa payları sırasıyla %40 ve %22, %3 ve %35 olarak analiz edilmiştir. Diğer bölge orijinli elmalara göre Amasya elması, sadece tüketicilerin tüketim memnuniyetini değil aynı zamanda arz zincirinde piyasa payını da maksimum kılmıştır.
Gıda İşlemede Plazma Teknolojisinin Uygulanması
Authors: Albayrak Aslı , Kılıç Gülden Başyiğit
Published: November 2020

Sağlıklı yaşama verilen önemin her geçen gün artmasıyla birlikte tüketicilerin çiğ ya da işlenmemiş gıdalara talebi artmaktadır. Ancak mikrobiyolojik kalitenin kontrol altına alınması amacıyla ısıl işlemin dışında alternatif tekniklerin arayışı ön plana çıkmaktadır. Isıl olmayan tekniklerin doğal aroma ve lezzeti koruması, mikrobiyolojik kaliteyi kontrol altına alırken ürünün yapısında herhangi bir değişikliğe neden olmaması gibi faktörler bu alternatif tekniklere teşvik etmektir. Plazma teknolojisi bu alternatif tekniklerden biridir. Maddenin dördüncü hali olarak bilinen plazma teknolojisi, pozitif ve negatif iyonların, serbest radikallerin, elektron ve foton formdaki yüklenmiş partiküllerin ve molekülleri içeren gazın, kısmen iyonize edilmesi olarak bilinmektedir. Plazma genellikle elektrik veya elektriksel boşaltım ya da kuvvetli bir radyasyon etkisi ile oluşur ya da oluşturulur. Plazmalar sıcaklıklarına, ısıl denge durumlarına ve basınçlarına göre sınıflandırılmaktadır. Gıdalarda, kontamine olmuş yüzeylerde, tıbbi aletlerin temizlenmesinde soğuk plazma tekniği kullanılmaktadır. Bu derlemede gıdalar üzerinde uygulanan plazma teknolojisi ve etkileri hakkında bilgi verilmiştir.
Applying the functional independence measure to the assessment of patients with mucopolysaccharidosis
Authors: Almeida Matos Marcos , Silva Lopes Paloma , Rodrigues Corsini Allan , Rodi Julia , Fong Chin-To
Published: November 2020

Introduction:
The aim of the study is to assess the functional independence of a group of patients with mucopolysaccharidosis using the Functional Independence Measure as a tool that accomplishes this purpose. 
Methods:
This is a cross-sectional study of patients with mucopolysaccharidosis. Our data was collected between June 2015 and July 2016. In addition to history of present illness and physical examination each study participant was asked to answer a questionnaire to specifically evaluate their functional independence using the Functional Independence Measure. The internal consistency of the Functional Independence Measure was assessed using Cronbach’s alpha coefficient.
Results:
We collected data on 20 patients with mucopolysaccharidosis. The average age was 10.8 (8.67-13.03) years, the average weight was 23.6 (19,91-27,37) kg and the average height was 1 (0.83-1.17) m. The most prevalent type of mucopolysaccharidosis in the study was type VI (n=14). The average total Functional Independence Measure score was 104.4 (97.61-111.19), the average for the Mobility domain was 73.50 (68.22-78.78) and the average for the Cognitive Function domain was 30.90 (28.68-33.13). The internal consistency of the entire questionnaire was 0.859, with values of 0.966 for the Mobility domain and 0.624 for the Cognitive Function domain. 
Conclusion:
The lowest Functional Independence Measure scores were obtained in the following sub-domains: Self-care, Locomotion and Cognitive Function. The Functional Independence Measure questionnaire demonstrated internal consistency for the evaluation of functional independence in patients with mucopolysaccharidosis, being able to value all the affected sub-domains separately.
Actuality and relevance of "The Peste" by Albert Camus
Authors: Botero Toro Eduardo
Published: November 2020

Time, a continuous line, not a loop: yesterday, today, and tomorrow satisfy the demands of a conception of the temporal inscribed in which it will always exist, supreme repetition, a before and after of things. Roma locuta, finite cause. It is from this conception of the temporal that nests the need for an exceptional authority to decide on the origin and on the destination. Tranquility for the herd: what the authority says, last word. From Roman law, the law is hard. And this conception is postulated as law, on the same level as another, which, unlike this one, does not require any authority to be true: we are born to die.But there will always be a thing that will insist on revealing itself either as saying, or as silence, inevitable and persevering. We represent time as a loop.If there is actuality in Camus's work, it is not because it has the value of a metaphor as much as it does because of the fact that we are living the probable concrete now as possible concrete. The unthinkable as a realization of what was nested in scientific speculation or in Hollywood horror movies: The Pandemic!
Disociación escapulo-torácica y trauma cerrado de arteria vertebral: reporte de un caso.
Authors: Vega Peña Neil Valentin , Dueñas Manuel Riveros , Riscanevo Bobadilla Angie Carolina
Published: November 2020

Descripción del caso:
Varón de 24 años que sufre accidente automovilístico con trauma penetrante de cuello y trauma cerrado cervico torácico izquierdo concomitante.

Hallazgos clínicos:
Shock hipovolémico, trauma en zona I cuello izquierdo, isquemia por trauma cerrado de vasos axilares y lesión por trauma cerrado del plexo braquial; producto de trauma de alto impacto. Sección de arteria vertebral por angiotomografia. Se diagnostica disociación escapulo-torácica y trauma de arteria vertebral.

Tratamiento y resultado:
Reconstrucción vascular arterio-venosa axilar, fasciotomías y abordaje no operatorio del trauma de arteria vertebral, con manejo diferido del trauma del plexo braquial. Sobrevida del paciente y su extremidad, con secuelas neurológicas mayores.

Relevancia clínica:
Es un caso de disociación escapulotorácica y lesión de arteria vertebral concomitante, siendo esta una asociación infrecuente y de alta morbi-mortalidad. El reconocimiento temprano de las lesiones y un abordaje multidisciplinario de este escenario de complejidad por medio de juntas quirúrgicas en varios niveles del proceso de atención, fueron determinantes para cambiar el pronóstico del paciente. Se presenta un análisis del diagnóstico, manejo y evolución; considerando el proceso de atención hospitalaria, toma consensuada de decisiones y el pronóstico en un paciente politraumatizado.
COVID-19: Adaptation of a model to predict healthcare resource needs in Valle del Cauca, Colombia
Authors: Iragorri Nicolas , Gómez-Restrepo Carlos , Barrett Kali , Herrera Socrates , Hurtado Isabel , Khan Yasin , Mac Stephen , Naimark David , Pechlivanoglou Petros , Rosselli Diego , Toro Dilian Francisca , Villamizar Pedro , Ximenes Raphael , Zapata Helmer , Sander Beate
Published: November 2020

Background: Valle del Cauca is the region with the fourth-highest number of COVID-19 cases in Colombia (>50,000 on September 7, 2020). Due to the lack of anti-COVID-19 therapies, decision-makers require timely and accurate data to estimate the incidence of disease and the availability of hospital resources to contain the pandemic.
Methods: We adapted an existing model to the local context to forecast COVID-19 incidence and hospital resource use assuming different scenarios: (1) the implementation of quarantine from September 1st to October 15th (average daily growth rate of 2%); (2-3) partial restrictions (at 4% and 8% growth rates); and (4) no restrictions, assuming a 10% growth rate. Previous scenarios with predictions from June to August were also presented. We estimated the number of new cases, diagnostic tests required, and the number of available hospital and intensive care unit (ICU) beds (with and without ventilators) for each scenario.
Results: We estimated 67,700 cases by October 15th when assuming the implementation of a quarantine, 80,400 and 101,500 cases when assuming partial restrictions at 4% and 8% infection rates, respectively, and 208,500 with no restrictions. According to different scenarios, the estimated demand for reverse transcription-polymerase chain reaction tests ranged from 202,000 to 1,610,600 between September 1st and October 15th. The model predicted depletion of hospital and ICU beds by September 20th if all restrictions were to be lifted and the infection growth rate increased to 10%.
Conclusion: Slowly lifting social distancing restrictions and reopening the economy is not expected to result in full resource depletion by October if the daily growth rate is maintained below 8%. Increasing the number of available beds provides a safeguard against slightly higher infection rates. Predictive models can be iteratively used to obtain nuanced predictions to aid decision-making
Spontaneous hemorrhage after external ventricular drain placement in the setting of low factor VII secondary to liver cirrhosis
Authors: Chua Melissa Ming Jie , Das Alvin S. , Losman Julie Aurore , Patel Nirav J. , Izzy Saef
Published: November 2020

Background:

Alterations in normal coagulation and hemostasis are critical issues that require special attention in the neurosurgical patient. These disorders pose unique challenges in the management of these patients who often have concurrent acute ischemic and hemorrhagic injuries. Although neurosurgical intervention in such cases may be unavoidable and potentially life-saving, these patients should be closely observed after instrumentation.

Case Description:

A 57-year-old male with liver cirrhosis secondary to amyloid light-chain amyloidosis was admitted to the intensive care unit for the management of delayed hydrocephalus. An external ventricular drain (EVD) was placed for the treatment and monitoring of hydrocephalus. Five days after EVD placement, a head computed tomography scan revealed a tract hemorrhage. However, on repeated imaging, the size of the hemorrhage continued to increase despite aggressive blood pressure control and several doses of phytonadione. Extensive coagulopathy workup was remarkable for low factor VII levels. In that setting, recombinant activated factor VII was administered to normalize factor VII levels, and the tract hemorrhage stabilized.

Conclusion:

To the best of our knowledge, this is the first case of spontaneous hemorrhage after EVD placement in the setting of liver cirrhosis-associated factor VII deficiency. Our case highlights the importance of identifying coagulation disorders in neurosurgical patients at high risk for coagulopathy and closely monitoring them postoperatively.
Lumbar revision microdiscectomy in patients with recurrent lumbar disc herniation: A single-center prospective series
Authors: Ahsan Md. Kamrul , Hossain Md. Rashedul , Khan Md. Shahidul Islam , Zaman Naznin , Ahmed Nazmin , Montemurro Nicola , Chaurasia Bipin
Published: November 2020

Background:

Recurrent lumbar disc herniation (RLDH) is a common complication following primary microdiscectomy. Notably, revision surgery for recurrent disc herniation typically warrants “aggressive discectomy (AD)” rather than microdiscectomy due to the marked changes in anatomy, including postoperative scar. Here, we prospectively evaluated clinical outcomes of 22 RLDH patients following secondary aggressive discectomy (AD).

Methods:

Records of 15 males and seven females averaging 41.7 years of age (range 21–60) who developed RLDH following primary microdiscectomy at the L4-5 (n = 12) and L5-S1 (n = 10) levels were studied. All patients underwent secondary AD for recurrent lesions (2014–2019). Multiple clinical parameters were assessed for these 22 patients. Outcomes were evaluated an average of 28.8 months postoperatively and included assessment of visual analog scales (VASs) and Japanese Orthopedic Association (JOA) Scores.

Results:

The VAS scores for back and radicular pain significantly improved, as did the JOA scores following surgery in all 22 patients after secondary AD.

Conclusion:

The authors concluded that secondary conventional revision discectomy (e.g., AD) effectively and safely managed RLDH.
IMPLEMENTASI APLIKASI QUIZIZZ PADA MATERI JARINGAN TUMBUHAN
Authors: Darisman Ambar Ismara Mula , Suprapto Purwati Kuswarini , Putra Rinaldi Rizal
Published: November 2020

Penelitian ini bertujuan untuk mengetahui pengaruh aplikasi Quizizz terhadap hasil belajar peserta didik pada materi jaringan pada tumbuhan di kelas XI MIPA salah satu SMA berada di perbatasan Kabupaten Garut. Penelitian ini dilaksanakan pada bulan Agustus 2019 sampai dengan bulan September 2019. Metode penelitian yang digunakan adalah quasi experimental dengan desain penelitian Nonequivalent control group design. Populasi dalam penelitian ini adalah seluruh kelas XI MIPA pada tahun 2019-2020. Sampel yang digunakan sebanyak dua kelas yang diambil dengan teknik porposive sampling. Teknik pengumpulan data berupa tes hasil belajar yang dilakukan sebelum dan sesudah kegiatan proses pembelajaran berlangsung. Instrumen yang digunakan adalah tes hasil belajar pada materi jaringan tumbuhan sebanyak 35 soal pilihan majemuk. Data hasil penelitian dianalisis dengan menggunakan uji t. Pada penelitian ini ditemukan peningkatan pada aspek kognitif hasil belajar terutama pada jenjang menganalisis, peningkatan ini terjadi karena aplikasi ini dikombinasikan dengan kegiatan praktikum. Selain itu, kebiasaan mencontek peserta didik dapat diminimalkan karena peserta didik terbiasa mengerjakan soal menggunakan aplikasi ini dengan randomisasi. Sehingga berdasarkan hasil penelitian dapat disimpulkan bahwa ada pengaruh Aplikasi Quizizz terhadap hasil belajar peserta didik pada materi jaringan tumbuhan.
Influence of genotype and environment on DNA methylation within shared index loci of schizophrenia and intelligence
Authors: Алфимова М.В. , Кондратьев Н.В. , Болгов М.И. , Габаева М.В. , Голимбет В.Е.
Published: November 2020

Целью работы была оценка вклада гаплотипов и полисредового риска (ПСР) в вариативность метилирования ДНК в локусах риска шизофрении. В периферической крови 70 пациентов методом одномолекулярного секвенирования Pacbio бисульфитно-конвертированной ДНК исследовали фрагменты внутри генов MIR137HR и CYP17A1 и вблизи SLC39A8. Из почти 1000 изученных цитозинов восемь были вариативно метилированы. Для семи из них обнаружено влияние генотипа. Дополнительно в одном случае найден эффект взаимодействия генотипа и ПСР и в одном - главный эффект ПСР. Таким образом, у больных в изученных участках вариативность метилирования преимущественно обусловлена структурой ДНК.

The study aimed to assess the contribution of haplotypes and polyenvironmental risk scores (PERS) to DNA methylation variability in schizophrenia index loci. In peripheral blood of 70 patients, fragments within the MIR137HR and CYP17A1 genes and near SLC39A8 were studied by Pacbio-based single-molecule real-time bisulfite sequencing. Of about 1000 cytosines, only eight were variably methylated. Genotypes influenced seven of them. Additionally, in one case an interaction effect of haplotype and PERS and in another case a main effect of PERS were found. Thus, in the studied schizophrenia loci, variable methylation is mainly due to DNA structure.
The effect of the interaction of human leukocyte antigen G (HLA-G) and preterm birth on clinical features of schizophrenia
Authors: Коровайцева Г.И. , Габаева М.В. , Юнилайнен О.А. , Голимбет В.Е.
Published: November 2020

Изучена связь INDEL полиморфизма гена HLA-G с шизофренией и ее клиническими особенностями с учетом средового фактора. Выявлено взаимодействие изучаемого полиморфизма и преждевременных родов и его влияние на выраженность позитивной симптоматики у женщин-носителей генотипа I/I.

The effect of INDEL polymorphism of the HLA-G gene on the risk of schizophrenia and its clinical features was studied. There was the interaction between this polymorphism and preterm birth as an environmental factor that influenced positive symptoms scores in women with the I/I genotype.
Genetic variants of the TCF4, LSM1, and CCDC60 genes are associated with schizophrenia
Authors: Бочарова А.В. , Марусин А.В. , Иванова С.А. , Федоренко О.Ю. , Семке А.В. , Степанов В.А.
Published: November 2020

Проведен анализ ассоциаций 30 однонуклеотидных полиморфизмов генов в группах больных шизофренией и контроле общей численностью 1020 образцов ДНК представителей русской популяции Сибирского региона. Для исследования были отобраны маркеры, показавшие ассоциацию с шизофренией или ее когнитивными эндофенотипами в широкогеномных ассоциативных исследованиях. Мультиплексное генотипирование проводилось на платформе «MassARRAY System 4». В результате проведенного анализа выявлены статистически значимые ассоциации, как для аллелей, так и для генотипов полиморфных вариантов генов TCF4, LSM1, CCDC60. Совокупность полученных данных указывает на то, что гены TCF4 и LSM1, вероятно, играют существенную роль в патогенезе шизофрении в популяциях мира.

1020 DNA samples of two groups of people (schizophrenia and control) from the Russian population were analyzed using 30 SNPs. As the analyzed markers, SNPs were selected that showed an association with schizophrenia or variability of cognitive abilities in genome-wide association studies. Multiplex genotyping was performed using the MassARRAY System 4 platform. As a result of the analysis, statistically significant associations were revealed for polymorphic variants of the TCF4, LSM1, CCDC60 genes. Our results confirm the role of the TCF4 and LSM1 genes in the schizophrenia pathogenesis in world populations.
The role of exon II HTR2A transcript isoforms in the development of mental pathologies and antipsychotic therapy prognosis
Authors: Грунина М.Н. , Заботина А.М. , Журавлев А.С. , Насырова Р.Ф. , Тараскина А.Е.
Published: November 2020

Психические расстройства ассоциированы с нарушением паттерна изоформ транскриптов экзона II гена HTR2A за счет преобладания альтернативной изоформы Е2-. При этом высокий уровень экспрессии изоформы Е2- ассоциирован с благоприятным прогнозом антипсихотической терапии.

The aim of the study was to analyze the role of exon II HTR2A gene transcript isoforms and rs6311 genetic variant in the development of mental pathologies and antipsychotic therapy prognosis. Alternative isoforms of exon II HTR2A are associated with the development of mental pathologies and is applicable to predict antipsychotic therapy outcome.
Post-GWAS studies of schizophrenia
Authors: Голимбет В.Е. , Голов А.К. , Царапкин Г.Ю. , Кондратьев Н.В. , Товмасян А.С. , Абашкин Д.А.
Published: November 2020

Представлены основные направления и полученные результаты проводимых авторами пост-GWAS исследований шизофрении, в том числе эпигенетические исследования, поиск новых регуляторных элементов генома, связанных с патогенезом этого заболевания, создание адекватных клеточных моделей для функциональных исследований.

We present the main directions and results of our post-GWAS studies of schizophrenia, including epigenetic studies, the search for enhancers located in schizophrenia GWAS regions and development of adequate cell models for functional studies.
Plasma exosomal alpha-synuclein in inherited forms of Parkinson’s disease
Authors: Кулабухова Д.Г. , Емельянов А.К. , Сенкевич К.А. , Грачева Е.В. , Милюхина И.В. , Верлов Н.А. , Варфоломеева Е.Ю. , Тимофеева А.А. , Шварцман А.Л. , Пчелина С.Н.
Published: November 2020

Предполагается, что экзосомы (микровезикулы размером 40-100 нм) могут играть ключевую роль в транспорте патогенных форм альфа-синуклеина при болезни Паркинсона (БП). В настоящем исследовании проведена оценка влияния мутаций в генах GBA и LRRK2 на уровень альфа-синуклеина экзосом плазмы крови. Показано, что мутации в генах GBA и LRRK2 не влияют на уровень альфа-синуклеина экзосом плазмы крови.

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder. Alpha-synuclein misfolding and aggregation resulting in neurototoxicity is a hallmark of PD. Exosomes (extrcellular vesicles 40-100 nm in size) can play a key role in the transport of pathogenic forms of alpha-synuclein. The aim of our work is to evaluate an effect of GBA and LRRK2 mutations on alpha-synuclein level in exosomes derived from peripheral blood plasma. No significant difference was found for exosomal alpha-synuclein levels patients with sporadic, GBA- and LRRK2- associated PD, PD with dementia compared to controls. Our results indicate that mutations in the LRRK2 and GBA genes do not influence on plasma exosomal alpha-synuclein level.
Neonatal case of dilated cardiomyopathy associated with novel MYH7 and TBX5 genetic variants
Authors: Злотина А.М. , Фомичева Ю.В. , Вершинина Т.Л. , Козырева А.А. , Киселёв А.М. , Первунина Т.М. , Васичкина Е.С. , Костарева А.А.
Published: November 2020

В настоящем исследовании описан новый случай выраженной дилатационной кардиомиопатии (ДКМП) с ранним дебютом. В семейном анамнезе присутствуют как фенотипы ДКМП разной степени тяжести, так и врожденные структурные пороки сердца. С использованием технологии высокопроизводительного секвенирования был охарактеризован полный спектр генетических вариантов в экзоме пациентки. В результате анализа выявлен новый вероятно-патогенный миссенс вариант в гене MYH7, кодирующем бета тяжелую цепь сердечного миозина (экзон 27, c.G3578T, p.R1193L). Кроме того, найден новый миссенс вариант с неопределенной клинической значимостью в гене TBX5, кодирующем транскрипционный фактор T-box 5 (экзон 7, c.T988A, p.C330S, ENST00000526441). Полученные данные свидетельствуют о том, что комбинация двух генетических вариантов в кардиальных генах может приводить к усилению клинического фенотипа ДКМП.

In the present study we report on a new case of severe early-onset dilated cardiomyopathy (DCM). In family medical history, both DCM phenotypes of different expressivity and congenital structural heart defects (CHDs) were revealed. Using high-throughput sequencing technology, we analyzed a full spectrum of genetic variants in the proband`s exome. On the results of whole-exome sequencing, we identified a novel likely-pathogenic missense variant in MYH7 encoding beta heavy chain of cardiac myosin (exon 27, c.G3578T, p.R1193L). Additionally, the proband possessed a novel missense variant of uncertain clinical significance in TBX5 (exon 7, c.T988A, p.C330S, ENST00000526441). The data obtained suggest that combination of two genetic variants in cardiac genes could cause the deterioration of the DCM clinical phenotype.
Analysis of MIR21 gene methylation level in blood vessels and leukocytes in carotid atherosclerosis by targeting bisulphite sequencing
Authors: Королёва Ю.А. , Марков А.В. , Слепцов А.А. , Зарубин А.А. , Муслимова Э.Ф. , Афанасьев С.А. , Кузнецов М.С. , Козлов Б.Н. , Назаренко М.С.
Published: November 2020

Методом таргетного бисульфитного секвенирования проанализирован уровень метилирования предполагаемого промоторного региона, CpG-островка и «тела» гена MIR21 в сосудах и лейкоцитах крови у пациентов с атеросклерозом сонных артерий, а также в лейкоцитах крови здоровых индивидов. Выявлено гипометилирование CpG-сайтов в гене MIR21 в сосудах по сравнению с лейкоцитами (вне зависимости от наличия заболевания). В атеросклеротической бляшке 4 последовательных CpG-сайта «тела» гена MIR21 оказались значимо гипометилированы относительно предлежащей макроскопически интактной части сонной артерии. Таким образом, установлена тканеспецифичность метилирования CpG-сайтов в гене MIR21 в сосудах, а также его связь с атеросклерозом сонных артерий.

We analyzed the DNA methylation level of MIR21 gene (proposed promoter, CpG island and gene body) by targeted bisulfite sequencing in blood vessels and leukocytes of patients with carotid artery atherosclerosis and in blood leukocytes of healthy individuals. We detected DNA hypomethylation at the CpG sites in the MIR21 gene in the blood vessels compared to the leukocytes (regardless of the disease). At the same time, 4 consecutive CpG sites of the MIR21 gene body were significantly hypomethylated in atherosclerotic carotid plaque compared to nearby macroscopically intact tissue. Thus, we have shown the tissue specificity at the CpG sites in the MIR21 gene for vessels and its association with carotid artery atherosclerosis.
Search for circular RNAs of the genes involved in lipid metabolism and atherogenesis
Authors: Носова Е.В. , Филиппенков И.Б. , Рожкова А.В. , Дмитриева В.Г. , Дергунов А.Д. , Лимборская С.А. , Дергунова Л.В.
Published: November 2020

Известно, что некодирующие регуляторные РНК влияют на функцию генов. Ранее мы обнаружили отрицательную корреляцию уровня холестерина липопротеинов высокой плотности (ХС-ЛВП) с содержанием транскриптов ряда генов, участвующих в метаболизме ЛВП и в атерогенезе. В данной работе проведен поиск циклических РНК генов HDLBP и TNFRSF1A, а также анализ их представленности в мононуклеарных клетках пациентов с различающимся содержанием ХС-ЛВП. С помощью биоинформатического анализа предсказаны сети возможных конкурентных взаимодействий миРНК с мРНК или циклоРНК данных генов. Сделано предположение, что обнаруженные циклические РНК играют роль конкурентных эндогенных молекул, участвующих в регуляции функционирования соответствующих генов.

Non-coding regulatory RNAs are known to affect gene function. We found earlier a negative correlation of high-density lipoprotein cholesterol (HDL-C) with transcripts of some genes involved in HDL metabolism and atherogenesis. In this work, we searched for circular RNA of HDLBP and TNFRSF1A genes in mononuclear cells of patients with different level of HDL-C. The network of competitive interactions of siRNAs with mRNA or circRNA of these genes are predicted by bioinformatic analysis. These circRNAs are suggested to function as the competitive endogenous molecules that are involved in the regulation of gene function.
LINE-1 retrotransposon demethylation is associated to atherosclerotic plaques destabilization
Authors: Шарыш Д.В. , Марков А.В. , Слепцов А.А. , Валиахметов Н.Р. , Королева Ю.А. , Казанцев А.Н. , Барбараш О.Л. , Назаренко М.С.
Published: November 2020

В работе проведен анализ уровня метилирования ретротранспозона LINE-1 в атеросклеротических бляшках сонных артерий, выделенных из них макрофагах и гладкомышечных клетках, а также в лейкоцитах периферической крови пациентов с клинически выраженным атеросклерозом и в лейкоцитах здоровых доноров. Выявлен сниженный уровень метилирования LINE-1 в атеросклеротических бляшках по сравнению с лейкоцитами крови пациентов, а также его связь с гистологическими признаками нестабильности атеросклеротической бляшки.

We analyzed the LINE-1 methylation level in carotid atherosclerotic plaques, macrophages and smooth muscle cells isolated from plaques and in the blood leukocytes of patients with clinically significant atherosclerosis and leukocytes of healthy donors. A reduced level of LINE-1 methylation in atherosclerotic plaques was detected compared to leukocytes, as well as it was associated with the histological features of carotid plaque instability.
Search for new genetic factors associated with the development of hypertrophic cardiomyopathy in the Russian population
Authors: Филатова Е.В. , Шадрина М.И. , Власов И.Н. , Крылова Н.С. , Маслова М.Ю. , Потешкина Н.Г. , Сломинский П.А.
Published: November 2020

Гипертрофическая кардиомиопатия (ГКМП) - самая распространённая форма наследственных заболеваний сердца с преимущественно аутосомно-доминантным типом наследования. Однако до сих пор не выявлены все гены, которые могут быть связаны с патогенезом ГКМП. В связи с этим, целью данной работы стали изучение и поиск новых генетических факторов, связанных развитием ГКМП в российской популяции.

Hypertrophic cardiomyopathy (HCM) is the most common form of inherited heart disease with a predominantly autosomal dominant type of inheritance. However, all genes that may be associated with the pathogenesis of HCMP have not yet been identified. In this regard, the aim of this work was to search for new genetic factors associated with the development of HCM in the Russian population.
A study of the expression of circular RNAs of the Ece1, Mvp, Egfem1, Cdyl and Rgs9 genes in transient cerebral ischemia model conditions
Authors: Валиева Л.В. , Филиппенков И.Б. , Ставчанский В.В. , Денисова А.Е. , Губский Л.В. , Лимборская С.А. , Дергунова Л.В.
Published: November 2020

Методом ПЦР в реальном времени в подкорковых структурах мозга крыс, содержащих очаг ишемического повреждения, показано активирующее влияние ишемии на экспрессию циклических РНК (циклоРНК) генов Ece1, Mvp, Egfem1 и Cdyl, а также репрессирующее влияние на экспрессию циклоРНК гена Rgs9. Биоинформатический анализ выявил возможные цис-регуляторные взаимодействия между микроРНК, а также циклоРНК и мРНК исследуемых генов, что указывает на функциональную роль данных циклоРНК в ответе клеток мозга на ишемию.

Using real-time PCR, the activating effect of ischemia on the expression of circular RNAs (circRNAs) of Ece1, Mvp, Egfem1 and Cdyl genes, as well as the repressing effect on the expression of circRNA of the Rgs9 gene, is shown in the subcortical structures of the rat brain containing the focus of ischemic damage. Bioinformatics analysis revealed possible cis-regulatory interactions between miRNAs, as well as circRNAs and mRNAs of the studied genes. The result indicates the functional role of these circRNAs in the response of brain cells to ischemia.
Modeling of pharmacokinetic processes of distribution of cisplatin in tumor tissues
Authors: Гиневский Д.А. , Ижевский П.В. , Шейно И.Н. , Левитова Д.Г.
Published: November 2020

Разработана математическая модель пространственно-временного распределения радиомодифицирующего агента химиотерапевтического препарата цисплатина с заданными физико-химическими свойствами на тканевом и клеточном уровнях организации биологической ткани. Эксперимент in silico позволил получить данные о кинетике внутриклеточного распределения цисплатина. Модель может быть адаптирована для определения 3D кинетики наночастиц, а также других препаратов для диагностики или терапии злокачественных новообразований.

A mathematical model of the space-time distribution of a radiomodifying agent - a chemotherapeutic drug - cisplatin with specified physical and chemical properties at the tissue and cellular levels of the biological tissue organization has been developed. The in silico experiment provided data on the kinetics of the intracellular distribution of cisplatin. The model can be adapted to determine the 3D kinetics of nanoparticles, as well as other drugs for the diagnosis or therapy of malignant neoplasms.
Identification of DNA differential methylation markers in breast tumors with different response to neoadjuvant chemotherapy
Authors: Сигин В.О. , Игнатова Е.О. , Литвяков Н.В. , Калинкин А.И. , Стрельников В.В. , Танас А.С.
Published: November 2020

Рак молочной железы (РМЖ) занимает лидирующие позиции среди новообразований у женщин по показателям заболеваемости и смертности. Несмотря на то, что неоадъювантная химиотерапия (НАХТ) позволяет добиться высоких результатов лечения, остается значительная часть пациенток с резидуальной опухолью и значимо худшим прогнозом. Мы провели широкогеномный анализ метилирования ДНК и выявили 33 гена, метилирование промоторных областей которых различается в опухолях молочной железы с различным ответом на НАХТ. Полученные результаты создают основу формирования систем маркеров метилирования ДНК для диагностики потенциальной чувствительности опухолей молочной железы к НАХТ.

Breast cancer (BC) occupies a leading position among neoplasms in women in terms of morbidity and mortality. Despite the advantages of neoadjuvant chemotherapy (NACT) which allows achieving high treatment results, a significant part of patients with residual tumor and significantly worse prognosis remains. We have carried out a genome-wide DNA methylation analysis and identified 33 genes methylation of which distinguishes breast tumors with different responses to NACT. Our findings provide the basis for development of test systems for diagnostics of potential sensitivity of breast tumors to NACT via DNA methylation analysis.
Analysis of the copy number of the BRCA1, NF-κB1 and PARP1 genes in patients with luminal B breast cancer
Authors: Цыганов М.М. , Ибрагимова М.К. , Певзнер А.М. , Гарбуков Е.Ю. , Гаптулбарова К.А. , Слонимская Е.М. , Литвяков Н.В.
Published: November 2020

Целью работы явилась оценка связи хромосомных аберраций генов BRCA1, NF-κB1, PARP1 в опухолевой ткани молочной железы с эффектом химиотерапии и прогнозом заболевания. В исследование включены 85 больных люминальным В раком молочной железы IIA-IIIB стадии, с морфологически верифицированным диагнозом, в возрасте 25-68 лет (47,8±1,1). Было установлено, что наибольшая частота делеций наблюдается в гене BRCA1 (36%, 30 случаев из 85). Частота амплификаций PARP1 в исследуемой группе больных РМЖ достигает 62% (53 случая из 85). Наименьшее число хромосомных аберраций наблюдается в гене NF-κB1, всего у 22 больных наблюдаются делеции и амплификации данного гена (26%). Показано, что делеция гена BRCA1 сопряжена с хорошим ответом на неоадъювантную химиотерапию вне зависимости от наличия хромосомных аберраций других генов. При этом амплификация PARP1 связана с плохим прогнозом заболевания.

The aim of the work was to assess the relationship of chromosomal aberrations of the BRCA1, NF-κB1, PARP1 genes in breast tumor tissue with the effect of chemotherapy and prognosis of the disease. The study included 85 patients with luminal stage IIA-IIIB breast cancer, with a morphologically verified diagnosis, aged 25-68 years (47.8±1.1). As a result of the study, the CNA frequency of the studied genes was estimated. It was found that the highest deletion rate is observed in the BRCA1 gene (36%, 30 cases out of 85). The frequency of amplification of PARP1 in the studied group of breast cancer patients reaches 62% (53 cases out of 85). The smallest number of chromosomal aberrations is observed in the NF-κB1 gene; in only 22 patients, deletions and amplifications of this gene are observed (26%). it was found that the deletion of the BRCA1 gene is associated with a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other genes. Moreover, amplification of PARP1 is associated with a poor prognosis of the disease.
Variants in the ASXL1 and DMNT3A genes are potential markers of the effectiveness of tyrosine kinase inhibitors therapy in chronic myeloid leukemia
Authors: Адильгереева Э.П. , Никитин А.Г. , Жегло Д.Г. , Шухов О.А. , Смирнихина С.А. , Челышева Е.Ю. , Лавров А.В. , Туркина А.Г. , Куцев С.И.
Published: November 2020

Хронический миелоидный лейкоз (ХМЛ) - онкогематологическое заболевание. Благодаря разработке таргетных препаратов ингибиторов тирозинкиназ (ИТК) достигнуты большие успехи в лечении ХМЛ, однако около 20-40% пациентов резистентны к терапии. Цель исследования - обнаружение экзомных вариантов, обуславливающих различную эффективность терапии ХМЛ. Нами было проведено севенирование экзома 60 пациентов, страдающих ХМЛ, на платформе Illumina NextSeq® 550 Sequencing System. Были обнаружены варианты в генах ASXL1, DNMT3A в группе пациентов, резистентных к терапии ИТК. Выявленные варианты могут быть ассоциированы с резистентностью к терапии ИТК.

Chronic myeloid leukemia (CML) is an oncohematological disease. Great success has been achieved in the treatment of CML due to the development of targeted drugs for tyrosine kinase inhibitors (TKI), but about 20-40% of patients are resistant to therapy. The aim of the study was the detection of exome variants causing resistance to CML therapy. We examined the exomes of 60 CML patients using the Illumina NextSeq® 550 Sequencing System platform. In the group of patients resistant to TKI therapy, loss-of-function variants were revealed in the ASXL1 and DNMT3A genes. Identified variants may be associated with resistance to TKI therapy.
Biodiesel Production from Sunflower Oil Using K2CO3 Impregnated Kaolin Novel Solid Base Catalyst
Authors: Jalalmanesh Shayan , Kazemeini Mohammad , rahmani mohamad hosein , Zehtab Salmasi Milad
Published: November 2020

Kaolin clay material was loaded with potassium carbonate by impregnation method as a novel effective and economical heterogeneous catalyst for biodiesel production of sunflower oil via the transesterification reaction. The structural and chemical properties of the produced catalysts were analyzed by several characterization tests including the BET-BJH, XRD, SEM and FTIR. Influence of the K2CO3 impregnation level was examined by comparing the catalytic activity of different produced catalysts. To expand the efficiency of transesterification reaction, parameters of reaction were optimized including; the molar ratio between methanol and oil, concentration of catalyst, and duration of the reaction. The highest yield of biodiesel over the K2CO3/kaolin catalyst was around 95.3 ± 1.2%. It was achieved using kaolin supports impregnated with 20 wt.% of K2CO3. The optimum reaction conditions were found to be catalyst reactor loading of 5 wt.%, reaction temperature of 65 °C, methanol: oil molar ratio of 6:1 and reaction duration time of 4 h.
Therapeutic Drug Monitoring: Performance of a FRET-Based Point-Of-Care Immunoassay for the Quantitation of Infliximab and Adalimumab in Blood
Authors: Ong Edgar , Huang Ruo , Kirkland Richard , Westin Stefan , Salbato Jared , Bray Kurt , Mimms Larry , Hale Michael
Published: November 2020

Two fast (<5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassays (Procise IFX™ and Procise ADL™) were developed for the quantitative detection of infliximab (IFX), adalimumab (ADL), and their respective biosimilars for use in therapeutic drug monitoring (TDM) using 20 µL of finger prick whole blood at the point-of-care or whole blood/serum in a central lab. Studies were performed to characterize analytical performance of the Procise IFX and the Procise ADL assays on the ProciseDx™ analyzer.

The Procise IFX and Procise ADL assays both showed good analytical performance with respect to sensitivity, specificity, linearity, and precision suitable for routine clinical use as well as excellent correlation to current commercial ELISA IFX and ADL measurement methods.

Results indicated that the Procise IFX and Procise ADL assays are sensitive, specific, and precise yielding results in less than 5 minutes from either whole blood or serum. This indicates the Procise IFX and Procise ADL assays are useful for obtaining fast and accurate IFX or ADL quantitation, thus avoiding delays inherent to current methods and enabling immediate drug level dosing decisions to be made during a single patient visit.
Adaptive Goal-Oriented Solver for the Linearized Poisson- Boltzmann Equation
Authors: Nakov Svetoslav , Sobakinskaya Ekaterina , Renger Thomas , Kraus Johannes
Published: November 2020

An adaptive finite element solver for the numerical calculation of the electrostatic coupling between molecules is developed and verified. The development is based on a derivation of a goal-oriented a posteriori error estimates for the electrostatic coupling. These estimates involve the consideration of the primal and adjoint problems for the electrostatic potential of the system. The accuracy of this solver is evaluated by numerical experiments on a series of problems with analytically known solutions. In addition, the solver is used to calculate electrostatic couplings between two chromophores, linked to polyproline helices of different lengths. All the numerical experiments are repeated by using the well known finite difference solvers MEAD and APBS, revealing the advantages of the present finite element solver
Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations
Authors: Wang Shan , Zhang Tian-Yi , Zhang Jian-Xin , Meng Huan , Chen Bi-Hong , Shu Wei
Published: November 2020

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of enamides and enolates with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.
La promesa unilateral y la responsabilidad civil
Authors: Huanco Piscoche Henry
Published: November 2020

La promesa unilateral es un instituto jurídico muy utilizado en la práctica diaria, principalmente para encontrar objetos extraviados, personas desaparecidas, recabar información sobre el paradero de algún delincuente o, en el ámbito comercial, en la emisión de pagarés; sin embargo, no ha sido debidamente analizada por la doctrina jurídica nacional, a diferencia de lo que sucede en la doctrina comparada. Por ello, en el presente artículo se desarrolla un minucioso análisis de sus antecedentes históricos, su regulación en los códigos civiles más influyentes, su tratamiento en los códigos civiles del Perú, las clases de “verdaderas” promesas unilaterales y la regulación de la responsabilidad civil derivada del incumplimiento de una promesa unilateral.
La función de juzgar. ¿Y quién juzga a quien juzga (...) y a quien juzga (...) y a quien juzga (...)?
Authors: Morales Bermúdez Escomel Ignacio
Published: November 2020

El presente trabajo busca tratar un tema siempre difícil como lo es el de la labor del juzgador en el Derecho. Resulta difícil determinar una forma de calificación capaz de señalar cuándo una decisión jurídica resulta o no apropiada. Uno podría llevar a cabo esta calificación apostando por ideales vinculados a la labor del juzgador; en este sentido, podríamos decir que aquél aplica las normas previamente establecidas sin descartar la posibilidad de generar interpretaciones de las mismas que contribuyan a crear nuevos criterios o nuevas reglas favorables a la sociedad. Si acaso no lo hiciese, entonces su labor estaría viciada. En este sentido, es objeto del presente trabajo preguntarse si acaso es posible que el juzgador se provea de mecanismos que le permitan mantener una actuación coherente y previsible, a fin de generar seguridad jurídica.
La Responsabilidad Civil en el Perú: avances, críticas y asuntos pendientes
Authors: Cieza Mora Jairo , Ortega Piana Marco Antonio , Montero Ordinola Gustavo Enrique
Published: November 2020

ADVOCATUS tuvo la oportunidad de entrevistar a tres abogados peruanos de gran trayectoria para que nos compartan sus reflexiones sobre la Responsabilidad Civil en nuestro marco normativo.