bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 Positivity Predicts Unresponsiveness to EGFR-Targeted Treatment in Metastatic Colorectal Cancer
Authors: Sartore-Bianchi Andrea , Amatu Alessio , Porcu Luca , Ghezzi Silvia , Lonardi Sara , Leone Francesco , Bergamo Francesca , Fenocchio Elisabetta , Martinelli Erika , Borelli Beatrice , Tosi Federica , Racca Patrizia , Valtorta Emanuele , Bonoldi Emanuela , Martino Cosimo , Vaghi Caterina , Marrapese Giovanna , Ciardiello Fortunato , Zagonel Vittorina , Bardelli Alberto , Trusolino Livio , Torri Valter , Marsoni Silvia , Siena Salvatore 
Published: April 2019

AbstractBackgroundHER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HER2 blockade. Preclinical findings show that it also might impair response to anti-epidermal growth factor receptor (EGFR) treatment.Subjects and MethodsPatients with KRAS exon 2 wild-type metastatic CRC underwent molecular screening of HER2 positivity by HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization). A sample of consecutive HER2-negative patients was selected as control. A regression modeling strategy was applied to identify predictors explaining the bulk of HER2 positivity and the association with response to previous anti-EGFR treatment.ResultsFrom August 2012 to April 2018, a total of 100 HER2-positive metastatic CRC tumors were detected out of 1,485 KRAS exon 2 wild-type screened patients (6.7%). HER2-positive patients show more frequently lung metastases (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.15–3.61; p = .014) and higher tumor burden (OR, 1.48; 95% CI, 1.10–2.01; p = .011), and tumors were more likely to be left sided (OR, 0.50; 95% CI, 0.22–1.11; p = .088). HER2-positive patients who received treatment with anti-EGFR agents (n = 79) showed poorer outcome (objective response rate, 31.2% vs. 46.9%, p = .031; progression-free survival, 5.7 months vs. 7 months, p = .087).ConclusionTesting for HER2 should be offered to all patients with metastatic CRC because the occurrence of this biomarker is unlikely to be predicted based on main clinicopathological features. Patients with HER2-amplified metastatic CRC are less likely to respond to anti-EGFR therapy.Implications for PracticePatients with HER2-amplified/overexpressed metastatic colorectal cancer (mCRC) harbor a driver actionable molecular alteration that has been shown in preclinical models to hamper efficacy of the anti-epidermal growth factor receptor (EGFR) targeted therapies. The present study confirmed that this molecular feature was associated with worse objective tumor response and shorter progression-free survival in response to previous anti-EGFR therapies. Moreover, it was found that the occurrence of this biomarker is unlikely to be predicted based on main clinicopathological features. Therefore, HER2 status assessment should be included in the molecular diagnostic workup of all mCRC for speedy referral to clinical trials encompassing HER2-targeted double blockade independently of previous anti-EGFR treatment.
Some challenges of treaty regulation of international relations in the field of environmental protection
Authors: Ilyinskaya O. I. 
Published: April 2019

International agreements and treaties in the field of environmental protection concluded in the 19th — first half of the 20th century, were, as a rule, the result of forced compromises, they were intended to solve urgent problems that had appeared or, at least, drew attention to limited areas (for example, the threat to a certain species, pollution of a marine area). In such cases, a convention was adopted to protect an endangered species or to limit emissions into the sea. As a result of this fragmented approach to environmental protection, an impressive but very heterogeneous system of conventions has emerged. Understanding of the unity of ecosystems implemented in the development of principles enshrined in the Stockholm Declaration of 1972 and the Rio Declaration of 1992 took place largely due to the rapid progress of science and technology. As a result, there has been a transition from “spontaneous” formation of international environmental standards to their consolidation around special principles of international environmental law. Also, a notable feature of many international treaties in the field of environmental protection — their “framework” character — is further analyzed. The adoption of framework agreements leads to the formation of complex sets of conventional documents consisting of several different, but in a certain way related to each other agreements. Considering the question of the effectiveness of such a legal instrument as a framework agreement, the author concludes that the origins of the problem of insufficient effectiveness of agreements in the field of environmental protection lie in the foundations of the existing economic system.
Evaluation of public effectiveness of the strategy for development of speed urban transport
Authors: Fedorova Mariya V. 
Published: April 2019

Abstract. Assessment of public efficiency of rapid urban transport development strategy is the final stage in the formation of a strategy for the development of rapid transport.
The rapid urban transport development strategy is distinguished by the following main characteristics:

significant initial investment, which in some cases is considered as an objective obstacle to adoption and implementation of the strategy;
long timeframes for implementation of the strategy;
timing of the achievement of the goals;
use of financial resources.

These characteristics enhance the current cost of the project. The process of measuring the results a new transport project implementation is complicated, because a significant part of the results is of external character and is not subject to cost measuring.
The peculiarities listed above prove the relevance of determination of public efficiency rapid urban transport development strategy. Considering the specifics of the object of the research, the comparison of costs and results of innovative transport product implementation should be carried out within assessment of its public efficiency.
The aim of this work is to develop a system of indicators for assessment of public efficiency of rapid urban transport development strategy; study of existing public efficiency assessment methods, search for their advantages and disadvantages, and research into maglev technology advantages.
The system of indicators proposed to assess public efficiency of rapid urban transport development strategy, considers all advantages of maglev technology and prioritises it in selecting rapid urban transport.
Study of hearing results of ossiculoplasty in patients with safe chronic suppurative otitis media
Authors: Kelkar Prasad A. , Hirekerur Jyoti V. 
Published: April 2019

<p class="abstract"><strong>Background:</strong> Ossicular discontinuity can occur as a result of erosion by chronic otitis media or due to trauma. Reconstruction of the ossicular chain aims to surgically optimize the middle ear transformer mechanism. The goal of this study was to devise a protocol to manage the ossicular discontinuity, provide good hearing to the patients and to demonstrate that use of ossicle for ossicular reconstruction is a safe, physiological, practical, successful and cost effective method.</p><p class="abstract"><strong>Methods:</strong> The present study is retrospective study of 50 patients who underwent ossiculoplasty in our institute over the period of 2 years. Most patients presented to us with a history of chronic intermittent ear discharge and decreased hearing. Detailed clinical examination included general examination and local examination of ear, nose and throat. Examination of ear included otoscopy, tuning fork tests, and examination under microscope. </p><p class="abstract"><strong>Results:</strong> The average pre-operative air-bone gap in patients with ossicular disruption was 34.95 dB and after ossiculoplasty was 12.93 dB. The mean air-bone closure after surgery was 27.88 dB. In most cases the post-operative air bone closure was within the range of 20 dB. The hearing results in ossiculoplasty are dependent on various factors but middle ear status in one of the most important factor in deciding the final outcome.</p><p class="abstract"><strong>Conclusions:</strong> The ossiculoplasty using autograft has stood the test of time and the results are superior to that of prosthesis. They have less rate of complications, are economic and easily available. The expertise to sculpt the ossicle can be easily developed with practice.</p><p> </p>
A lei 10.639/03 como instrumento político-pedagógico na perspectiva do combate ao racismo na educação básica
Authors: Nunes Antonio de Assis Cruz , Silva Andréa Luisa Frazão , Rocha Luis Félix De Barros Vieira , Dos Santos Clenia De Jesus Pereira 
Published: April 2019

O presente artigo trata da obrigatoriedade de implementação da Lei nº 10.639/2003 no âmbito da Educação Básica, assim como apontar perspectivas das/os professoras/es utilizarem em de sala de aula. O estudo faz, primeiramente, uma breve trajetória histórica de algumas ações dos movimentos sociais negros no Brasil até a aprovação da Lei 10.63 de 2003. A discussão ancorou-se, basicamente, por meios da referida Lei e seus congêneres, como: a Resolução Nº 01/2003, O Parecer Nº 03/2004, O Plano Nacional de Implementação das Diretrizes Curriculares Nacionais para Educação das Relações Etinico-Raciais e para o Ensino de História e Cultura Afrobrasileira e Africana e autores que tratam sobre a temática das relações étnico-raciais, tais como Santos (2005), Siss (2003), Rocha (2011), dentre outros. A pesquisa concluiu que a Lei 10.639/03 pode se constituir como um forte instrumento político e pedagógico para o combate do preconceito e discriminação racial no contexto da Educação Básica, especificamente no Ensino Fundamental .
PROBLEMS OF USING MOLECULAR-GENETIC METHODS FOR THE STUDY OF FISH FEEDING
Authors: Dzyuba E. V. , Kondratov I. G. , Kirilchik S. V. , Khanaev I. V. , Denikina N. N. , Nebesnykh I. A. , Bogdanov B. E. , Polynov V. A. , Kulakova N. V. 
Published: April 2019

The aim of the study was an approbation of molecular-genetic methods for an analysis of contents of fish stomachs of Abyssocottus korotneffi Berg, 1906, as an example.Methods. Sampling carried out at the board of the research vessel «G.Yu. Vereshchagin» in August 2017 in the northern basin of Lake Baikal. To study a fish feeding, testing of a DNA extraction methods and PCR conditions was performed. A fragments of the CO1 gene were amplified from total DNA isolated from the contents of the fish stomachs. The composition of food was studied based on the analysis of nucleotide sequences cloned into the plasmid pJET vector.Results. One species of amphipods closest to Odontogammarus calculator Dybowsky, 1874 was detected in fish food. In addition, sequences of cottoid fish were found in the studied samples. To date, information about a presence of fish in the food spectrum of this species was absent.Conclusions. The main problem of using molecular-genetic methods in studies of fish food spectrum is not enough number of data of voucher sequences of the CO1 gene of Baikal organisms in the genetic databases. Despite on advantages of analysis of the CO1 gene in studies of fish food feeding, this approach does not allow to distinguish between organisms of the same species.
GEOECOLOGICAL DIAGNOSTICS OF THE REGIONS IN THE CENTRALBLACK SOIL REGION
Authors: Kurolap S. A. , Yakovenko N. V. , Fedotov V. I. , Mikhno V. B. , Kostyleva L. N. 
Published: April 2019

Aim.The aim is geoecological diagnostics of regions of the Central Black Soil Region on the basis of which the areas with different degree of tension of a technogenic and medicoecological situation have been revealed. Material and methods of research. System, comparative-geographical, geoinformation, historical, statistical methods of research, as well as software packages MS Excel and Statistica have been used. The database has been formed in retrospect for the period 2006-2015. About 50 public health criteria and about 200 potential risk factors have been analyzed. 9 key (indicator) criteria have been selected.Results.The authors propose an algorithm to perform geoecological diagnostics of the large region. The correlations between integral estimation criteria of levels of technogenic loadings and parameters of public health have been calculated. The positive correlations of weak and medium degree indicate the presence of stable trends: the increase in the levels of technogenic loads on the environment of the regions is an unfavorable "response" on the part of the population (the growth of environmentally caused pathology and, first of all, malignant neoplasms, as well as congenital anomalies in children). It is established that among the regions of the Central Black Soil Region this pattern is more pronounced for the area of the Belgorod region, where the environmental situation is much more contrasting, and the level of technogenic impact in the urban agglomeration zone is higher than, for example, in the Voronezh region.Conclusion.In this scientific paper, the authors have solved the actual practice-oriented problem in the field of geoecological researches, namely, they have developed the method of geoecodiagnostics of a large region, which allows to quickly and reliably determine the degree of technogenic load on the area. The analysis of the obtained data allowed us to reveal the regularities of the formation of the geoecological situation in the area of the Central Black Soil Region, to formulate the main directions of environmental policy and to predict the dynamics of the geoecological situation development.
DIFFERENTIATION OF STRUCTURE LANDSCAPE AND ENVIRONMENTAL INDICATORS
Authors: Medvedev I. F. , Gubarev D. I. , Derevyagin S. S. , Nesvetaev M. Yu. , Verin A. Yu. , Mishchenko N. V. 
Published: April 2019

Aim.To identify the degree of influence of the morphological heterogeneity of the territory on the ecological state of the agricultural landscape.MethodsThe study was conducted on an area of 608.5 hectares and a horizontal dissection factor of 8.36 km/km2. For the observations, distributed test pads measuring 10 m2 were used. On each type of facies, test sites were laid on arable land in triplicate. We used standard research methods using GIS. Existing thematic terrain maps were digitized and a digital elevation model based on a topographic survey of the terrain was created. Calculations and visualization of data are made using and based on the ArcGIS and Microsoft Excel software.Results.The degree of influence of the types of facies of the landscape area on individual criteria and indicators of arable land productivity (microclimatic indicators, water properties of the soil, elements of fertility) has been established. Spatial ecologically justified differentiation of types of tracts into facies types has been carried out.Main conclusions.The slopes of the northern exposure (I-IVn) have the highest ecological stability. They lead in the content of productive moisture, mobile phosphorus and potassium. The facies of the slopes of the southern exposure (I-IVs) lead by insolation, the content of humus and nitrate nitrogen. The content of heavy metals in the soils and wheat yield is higher on the southern slopes and second-order watersheds (IVn). The maximum productivity of 2.9 t/ha was obtained on the watershed type of facies (V). A close relationship was established (r = -0.72) between productivity and pH of soil, medium – with mobile forms of phosphorus (r = 0.59) and potassium (r = 0.84).
Três movimentos metodológicos para o estudo da Biblioteca Pessoal Alda Lodi
Authors: Amorim Brian Diniz , Gomes Maria Laura Magalhães 
Published: April 2019

O artigo apresenta três movimentos metodológicos empreendidos em uma pesquisa realizada tomando como fonte e objeto a biblioteca da professora Alda Lodi. O texto é centrado na apresentação e discussão das escolhas metodológicas realizadas nos três movimentos empreendidos: o primeiro, a constituição do corpus de pesquisa através de uma catalogação dos livros da biblioteca; o segundo, uma investigação dos autores mais citados nos livros da biblioteca mediante o mapeamento das referências bibliográficas; o terceiro, a escolha de dois livros para uma análise mais aprofundada e a investigação das marcas de leitor presentes nesses livros. Destacam-se as implicações das escolhas para a pesquisa, assim como defende-se a adoção de procedimentos metodológicos adequados e posteriores ao conhecimento dos objetos de pesquisa. Por fim, ressalta-se a possibilidade do uso das marcas de leitor na compreensão dos usos do texto pelo professor-leitor.
TEACHING SUPERVISION OF MADRASAH HEADMASTER BASED ON PESANTREN CULTURE
Authors: Nadhirin Nadhirin 
Published: April 2019

<p><em>T</em><em>o realize the learning, it takes teaching supervision activities. The target of supervision is the teaching staff. The purpose of this paper is to find out (1) how the teaching supervision activities in madrasah is (2) how the techniques and approaches of supervision is (3) how the supervision of teaching in the madrasah is based on pesantren culture. The research method is library research with the technique of collecting the source of supervision theory of teaching through literature study and analysis technique with deductive-inductive thinking pattern. The results showed that (1) supervision of teaching in madarash is a function of leadership communication with pesantren culture so the relationship between teachers with the headmaster or between teachers and students is to follow the pattern of relationship between kyai and santri (2) supervision approaches with a limited personal relationship approach and in an informal setting are much more effective because supervisory activities between teacher and headmaster are not open (3) teaching supervision uses cultural organization group of religion technique (4) teaching supervision uses situational integrated approach.</em></p>
Optimization of Vaccine Virus Accumulation in the Development of Smallpox Drugs Based on Cell Cultures
Authors: Ovchinnikov A. V. , Borisevich G. V. , Terent’ev A. I. , Pashchenko Yu. I. , Krotkov V. T. , Marchenko V. N. , Borisevich S. V. , Kuznetsov S. L. 
Published: April 2019

Objective. Optimization of vaccine virus cultivation in the suspended cell culture BHK-21 for infectious activity increment of virus-containing suspension as the base material for smallpox vaccine preparations. Materials and methods. We used suspended culture line of the cells BHK-21 of 72-hour age and nutrient medium of the MEM type in accordance with the guidelines on preparation in our studies. For challenging of the cells, vaccine virus (strain B-51) was used. The virus was adapted through three consequent passages on horion-allantois shell of developing chicken embryos of commercial dermovaccine series 449а at the premises of the Federal State Budgetary Institution “the 48th Central Research Institute” of the Ministry of Defense of the Russian Federation. Information on its genetic features is absent. Cultivation and precipitation of infected cells BHK-21 was carried out in bioreactor with priming volume of 1 liter at (36.5±0.5) °C and aeration with air mixture with varying content of CO2. Results and conclusions. Gas massexchange intensity was enhanced alongside simultaneous maintaining of sparing hydrodynamic conditions for mixing suspended cell cultures in bioreactor. Two-fold increase (up to (4.48±0.63)·109 cell/l) in suspended BHK-21 cell culture concentration at the end of reproduction cycle was achieved. Concentration of the vaccine virus was 3–5 times raised, from (8.1±0.3) lg PFU (plaque forming unit)/ml up to the level of infectious activity – (8.8±0.3) lg PFU/ml. Specific multiplicity of cell infection in recalculation per a cell was 1–5 PFU/cell and by virus yield – 20–100 PFU/cell. Enhanced infectious activity of the virus in concentrated suspension of infected BHK-21 cells substantiates the perspectives of the proposed method for improvement of vaccine virus accumulation phase in the development of anti-smallpox preparations based on cell cultures.
Psychometric Properties of Patient-Reported Outcome Measures for Periacetabular Osteotomy
Authors: Wasko Marcin K. , Yanik Elizabeth L. , Pascual-Garrido Cecilia , Clohisy John C. 
Published: April 2019

Background:
Appropriate patient-reported outcome measures are paramount to determine the clinical relevance of change experienced by patients after a surgical procedure. The purpose of this study was to evaluate the psychometric properties of 3 patient-reported outcome measures (Hip disability and Osteoarthritis Outcome Score [HOOS], modified Harris hip score, and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in a large population of patients treated with periacetabular osteotomy for symptomatic developmental dysplasia of the hip.

Methods:
Patients who underwent a periacetabular osteotomy for acetabular dysplasia between October 2011 and October 2016 completed multiple questionnaires preoperatively and at the 1-year follow-up. Internal consistency for subscores was evaluated with the Cronbach alpha. Validity was assessed against the Short Form-12. Interpretability included the calculation of the distribution of scores, floor and ceiling effects, and the minimal clinically important difference. Responsiveness was assessed by correlating the score changes with the Global Perceived Effect score.

Results:
Of 294 patients, 246 (84%) were female. The median age was 21 years (interquartile range, 17 to 29 years). All WOMAC and HOOS subscores demonstrated adequate internal consistency, and none of the modified Harris hip score components did. All scores except the WOMAC stiffness score exhibited adequate validity and interpretability, with no floor and ceiling effects over 15%. For the HOOS subscores, the minimal clinically important difference was 10.3 for pain, 10.2 for symptoms, 12.6 for sports and recreation, 11.2 for quality of life, and 10.8 for activities of daily living. The minimal clinically important difference for the modified Harris hip score was 7.4. For the WOMAC subscores, the minimal clinically important difference was 10.8 for pain, 12.9 for stiffness, 10.8 for physical, and 10.4 for total. All scores demonstrated adequate responsiveness.

Conclusions:
The HOOS, WOMAC, and modified Harris hip score have adequate psychometric properties for use in patients undergoing periacetabular osteotomy, with minor shortcomings. Among the scores analyzed, the HOOS appears to be the most appropriate measure of patient-reported outcome in patients undergoing periacetabular osteotomy.

Clinical Relevance:
By establishing the psychometric properties of patient-reported outcome measures for periacetabular osteotomy, this study enables a more informed choice of measures for clinical practice and research. The estimated minimal clinically important difference values will facilitate understanding the importance of change in patient-reported outcomes after a surgical procedure in a clinical setting and sample size calculation for further studies.