bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous exposure and hotspots for malaria vectors at three study sites in Uganda
Authors: Kang Su Yun , Battle Katherine E. , Gibson Harry S. , Cooper Laura V. , Maxwell Kilama , Kamya Moses , Lindsay Steven W. , Dorsey Grant , Greenhouse Bryan , Rodriguez-Barraquer Isabel , Reiner Robert C. Jr. , Smith David L. , Bisanzio Donal
Published: July 2018

Background: Heterogeneity in malaria transmission has household, temporal, and spatial components. These factors are relevant for improving the efficiency of malaria control by targeting heterogeneity. To quantify variation, we analyzed mosquito counts from entomological surveillance conducted at three study sites in Uganda that varied in malaria transmission intensity.

Methods: Using a Bayesian zero-inflated negative binomial model, validated via a comprehensive simulation study, we quantified household differences in malaria vector density and examined its spatial distribution. We introduced a novel approach for identifying changes in malaria hotspots over time by computing the Getis-Ord statistic on ratios of household biting propensities for different scenarios. We also explored the association of household biting propensities with housing and environmental covariates.

Results: In each site, there was evidence for hot and cold spots, spatial patterns associated with urbanicity, elevation, or other environmental covariates. We found some differences in the hotspots in rainy vs. dry seasons or before vs. after the application of control interventions. Housing quality explained a portion of the variation among households in mosquito counts.

Conclusion: This work provided an improved understanding of heterogeneity in malaria vector density at the three study sites in Uganda and offered a valuable opportunity for assessing whether interventions could be spatially targeted to be aimed at hotspots of malaria risk. Indoor residual spraying was shown to be a successful measure of vector control interventions in Tororo, Uganda.  Cement walls, brick floors, closed eaves, screened airbricks, and tiled roofs were features of a house that had shown protective effects towards malaria risk. Improvements in house quality should be recommended as a supplementary measure for malaria control.
THE VASCULAR COMPONENT IN VASCULAR PLEXUSES OF THE BRAIN VENTRICLES
Authors: Гасанова Илаха , Gasanova I. , Куница Виктор , Kunitsa V. , Гасанли Заргул , Gasanli Z. , Мясникова Ольга , Myasnikova O. , Аллахвердиев Эльнур , Allakhverdiyev E.
Published: July 2018

Vascular plexus of the ventricles of the brain play an important role in the formation of liquor, involved in the exchange, trophic, protective, homeostatic function of the brain. The role of the vascular component of the choroid plexus is not fully understood. The authors studied age-related changes in the vascular component of ventricular plexus in rats. The revealed involutional changes may be the cause of some brain diseases, accompanied by a disorder of the synthesis of cerebrospinal fluid
Advertising in Health Insurance Markets
Authors: Shapiro Bradley T.
Published: July 2018

The effects of television advertising in the market for health insurance are of distinct interest to both firms and regulators. Regulators are concerned about firms potentially using ads to “cream skim,” or attract an advantageous risk pool, as well as the potential for firms to use misinformation to take advantage of the elderly. Firms are interested in using advertising to acquire potentially highly profitable seniors. Meanwhile, health insurance is a useful setting to study the mechanisms through which advertising could work. Using the discontinuity in advertising exposure created by the borders of television markets, this study estimates the effects of advertising on consumer choice in health insurance. Television advertising has a small effect on brand enrollments, making advertising a relatively expensive means of acquiring customers. Heterogeneous effects point to advertising being more effective in less healthy counties, which runs opposite to the concern of cream skimming. Leveraging the unilateral cessation of advertising by United-Healthcare, evidence is provided that the small advertising effect is not explained by a prisoner’s dilemma equilibrium. An analysis of longer-run effects of advertising shows that advertising effects are short lived, further decreasing the potential of advertising to create long-run value to the firm.
Social Learning and the Design of New Experience Goods
Authors: Feldman Pnina , Papanastasiou Yiangos , Segev Ella
Published: July 2018

Consumers often consult the reviews of their peers before deciding whether to purchase a new experience good; however, their initial quality expectations are typically set by the product’s observable attributes. This paper focuses on the implications of social learning for a monopolist firm’s choice of product design. In our model, the firm’s design choice determines the product’s ex ante expected quality, and designs associated with (stochastically) higher quality incur higher costs of production. Consumers are forward-looking social learners, and may choose to strategically delay their purchase in anticipation of product reviews. In this setting, we find that the firm’s optimal policy differs significantly depending on the level of the ex ante quality uncertainty surrounding the product. In comparison to the case where there is no social learning, we show that (i) when the uncertainty is relatively low, the firm opts for a product of inferior design accompanied by a lower price, while (ii) when the uncertainty is high, the firm chooses a product of superior design accompanied by a higher price; interestingly, we find that the product’s expected quality decreases either in the absolute sense (in the former case), or relative to the product’s price (in the latter case). We further establish that, contrary to conventional knowledge, social learning can have an ex ante negative impact on the firm’s profit, in particular when the consumers are sufficiently forward-looking. Conversely, we find that the presence of social learning tends to be beneficial for the consumers only provided they are sufficiently forward-looking.

This paper was accepted by Serguei Netessine, operations management.
Modinha: Um estudo etimológico sobre o termo
Authors: Monteiro José Fernando Saroba
Published: July 2018

Procuramos aqui descrever a etimologia do termo modinha, que designa um gênero que está nas raízes da música popular tanto do Brasil quanto de Portugal. Surgida da moda portuguesa, que migrou dos meios rurais para os grandes centros urbanos e colônias do Império Português, entre os séculos XVII e XVIII, a modinha tem suas origens etimológicas em períodos ainda mais antigos, remontando a presença romana na Península Ibérica, onde através da sobrevivência de vocábulos da língua latina, se originou a palavra “moda”, ganhando depois seu diminutivo e o indicativo de sua presença e permanência na América portuguesa, passando a ser chamada de “modinha brasileira”.
Apontamentos sobre Bernardo Élis biógrafo (1973-1980)
Authors: Assumpção Albertina Vicentini , De Paula Gabriel
Published: July 2018

O artigo objetiva apresentar, suscintamente, algumas modalidades de escrita de Bernardo Élis no exercício de biógrafo de vultos goianos, especialmente a sua biografia do General Xavier Curado. Insiste nos tons e na patrimonialização cedidos aos biografados e na autolegitimação do biógrafo. Uma questão central na obra de Bernardo Élis é o desejo de inclusão da região goiana no contexto nacional. A literatura de Élis busca reduzir a distância entre o litoral e o sertão. Suas obras caminham no sentido de pensar o Brasil de forma mais ampla, escapando do monopólio narrativo do centro-sul.
Transgredindo as margens e forjando histórias: a imprensa negra na fronteira Brasil-Uruguai no Pós-Abolição
Authors: Silva Fernanda Oliveira da
Published: July 2018

Neste artigo analiso a imprensa negra da região de fronteira Brasil-Uruguai, mais especificamente das cidades de Melo e Pelotas: A Alvorada (Pelotas, 1907-1965), Acción (Melo, 1934-1952) e Orientacion (Melo, 1941-1945). A experiência destes periódicos é o fio condutor, cujo foco está em Acción, criado como porta voz do Centro Uruguay, clube negro criado em Melo em 1923. Dentre as conclusões explicito que por meio da tribuna pública, imprensa, foram transgredidas as margens, tanto uma referência aos trânsitos em uma região de fronteira, quanto às vivências da racialização, e forjada uma história para a nação uruguaia que se conectava com o Brasil, denunciava a racialização reinante e inseria a população negra dentre os atores daquela história já plenamente conhecida pelos pagos uruguaios.
Histórias em negrito: uma entrevista com a Dra. Martha Rosa Figueira Queiroz
Authors: Pinto Ana Flávia Magalhães , Ramos Ana Flávia Cernic
Published: July 2018

Entrevista com Martha Rosa Figueira Queiroz.
Good quality digital literacy: Making online life safer for pupils
Authors: Feuchtwang Anna
Published: July 2018

Good quality RSE should promote digital literacy to help children navigate the risks they encounter online but also help them understand how their choices can have a lasting impact on others, Anna Feuchtwang explains
Celebrating 70 years of nursing in an evolving NHS
Authors: Mortimore Gerri
Published: July 2018

Gerri Mortimore, Lecturer at the University of Derby, discusses the changing role of nurses in the NHS since its creation in 1948
Decision making in early-stage colorectal cancer treatments: a literature review
Authors: Westwood Clare , McSherry Robert , Lee Tom , Bettany-Saltikov Josette
Published: July 2018

Background:

The introduction of the National Bowel Cancer Screening Programme has led to an increase in colorectal cancer diagnosed at an early stage. Advances in the options for treatmentof early-stage disease may have similar survival benefits but different risks and side effects. The decision on treatment for early stage bowel cancers can therefore be described as preference sensitive.

Method:

A literature review was conducted of 12 studies and reviews published 2007–2017, focusing on patient involvement in decisions on treatment following a diagnosis of colorectal cancer. The review covered both patient and clinician perspectives.

Results:

The review highlighted key themes that influence how far patients are involved in decisions regarding treatment. These themes include: patient understanding of the preference-sensitive nature of the decision, time pressures and perceived inapplicability of involving patients.

Conclusion:

Further studies are necessary to understand the experiences of patients and clinicians making treatment decisions in the context of early colorectal cancer, including polyp cancers. There is a lack of studies specifically addressing clinician experiences in this area.
Prevention of pressure ulcers in community care settings
Authors: Nazarko Linda
Published: July 2018

Linda Nazarko looks at how to identify and manage these increasingly common sores
Providing a ‘secure hub’
Authors: Bergin Joelle
Published: July 2018

What should practitioners begin to think about when a two-year-old in their care is diagnosed with a muscular degenerative condition? Joelle Bergin suggests a practical approach that supports the child, family and staff.
Come into my parlour
Authors: Chapman Ailsa
Published: July 2018

Ailsa Chapman reflects on how the warm weather has had a positive impact on learning, providing inspiration for creative activities such as making ice cream parlours using tuff trays.
Lines in the sand
Authors: Harries Judith
Published: July 2018

Now is a fantastic time for children to create artwork inspired by the seaside. Judith Harries suggests resources and ideas that will set children on an imaginative quest to model their favourite seaside objects.
Germinação de sementes armazenadas de Belamcanda chinensis (L.) DC
Authors: Silva Girlânio Holanda , Baldini Lenise Santos , Tomaz Camila Aquino , Rossi Rubiana Falopa , Nakagawa João
Published: July 2018

The leopard lily (Belamcanda chinensis) is an exotic ornamental Iridaceae in Brazil and cultivated as a medicinal plant in its countries of origin (China and Japan). It is propagated by rhizomes and seeds; however, the viability of these seeds after storage remains unknown. The aim of this study was to evaluate the germinability of stored B. chinensis seeds. Seeds harvested between March and April 2010, 2011, 2012 and 2013 were separated by year and stored in paper bags in a room without relative humidity and temperature control. Seeds from these four years were analyzed for moisture content, 100-seed weight and germination index. The freshly harvested seeds (2013) and those stored for one year (2012) exhibited 72% and 41% germination, respectively, and 80% and 47% primary root emission at the end of 20 weeks. However, seeds stored for two and three years (2010 and 2011) didnot germinate. B. chinensis seeds remained viable for up to one year of storage.
Plotting the map projection graticule involving discontinuities based on combined sampling
Authors: Bayer Tomáš
Published: July 2018

This article presents  new algorithm for interval plotting the projection graticule on the interval $\varOmega=\varOmega_{\varphi}\times\varOmega_{\lambda}$ based on the combined sampling technique. The proposed method synthesizes uniform and adaptive sampling approaches and treats discontinuities of the coordinate functions $F,G$. A full set of the projection constant values represented by the projection pole $K=[\varphi_{k},\lambda_{k}]$, two standard parallels $\varphi_{1},\varphi_{2}$ and the central meridian shift $\lambda_{0}^{\prime}$ are supported. In accordance with the discontinuity direction it utilizes a subdivision of the given latitude/longitude intervals $\varOmega_{\varphi}=[\underline{\varphi},\overline{\varphi}]$, $\varOmega_{\lambda}=[\underline{\lambda},\overline{\lambda}]$ to the set of disjoint subintervals $\varOmega_{k,\varphi}^{g},$$\varOmega_{k,\lambda}^{g}$ forming tiles without internal singularities, containing only "good" data; their parameters can be easily adjusted. Each graticule tile borders generated over $\varOmega_{k}^{g}=\varOmega_{k,\varphi}^{g}\times\varOmega_{k,\lambda}^{g}$ run along singularities. For combined sampling with the given threshold $\overline{\alpha}$ between adjacent segments of the polygonal approximation the recursive approach has been used; meridian/parallel offsets are $\Delta\varphi,\Delta\lambda$. Finally, several tests of the proposed algorithms are involved.
Geodetic work at the archaeological site Tell el-Retaba
Authors: Stopková Eva
Published: July 2018

The paper summarizes the geodetic contribution for the Slovak team within the joint Polish-Slovak archaeological mission at Tell el-Retaba in Egypt. Surveying work at archaeological excavations is usually influenced by somewhat specific subject of study and extreme conditions, especially at the missions in the developing countries. The case study describes spatial data development according to the archaeological conventions in order to document spatial relationships between the objects in excavated trenches. The long-term sustainability of surveying work at the site has been ensured by detailed metadata recording. Except the trench mapping, Digital Elevation Model has been calculated for the study area and for the north-eastern part of the site, with promising preliminary results for further detection and modelling of archaeological structures. In general, topographic mapping together with modern technologies like Photogrammetry, Satellite Imagery, and Remote Sensing provide valuable data sources for spatial and statistical modelling of the sites; and the results offer a different perspective for the archaeological research.
Feedbacks in Non-equilibrium Oxidative Plasma Reacting with Polyethylene
Authors: Kadnikov D. V. , Ovtsyn A. A. , Shibaev S. A. , Smirnov S. A.
Published: July 2018

The experimental results on studies of loading effect at the action of a glow DC discharge in oxygen and air on polyethylene film are presented. At the increase in a polymer amount under a treatment the specific rates of etching and CO2, CO, H2O, H2 product formation rates are decreased. The gas temperature is changed slightly. The reduced electric field strength is increased in oxygen plasma and decreased in air plasma.
Utilisation of the High Speed Camera for the Pin-hole Discharge Diagnostics
Authors: Kozakova Z. , Krcma F. , Drimalkova L. , Hlochova L.
Published: July 2018

The high speed camera was utilised for plasma diagnostics of the DC pin-hole discharge in electrolyte solutions. Two discharge modes were determined. Plasma channels were observed either in the bubble or outside the bubble in the bulk solution, which confirms both thermal and electron theory of the discharge ignition in liquid. In the diaphragm discharge, plasma streamers were better visible on the cathode side of the dielectric barrier because they formed significantly longer channels.
Plasma Assisted Generation of Micro- and Nanoparticles
Authors: Veklich A. , Lebid A. , Tmenova T. , Boretskij V. , Cressault Y. , Valensi F. , Lopatko K. , Aftandilyants Y.
Published: July 2018

In this research, the peculiarities of micro- and nanoparticles generation are considered. Two techniques of micro- and nanoparticles' formation using electric arc and underwater discharge plasma sources are proposed. Molybdenum oxide crystals were deposited on side surface of the bottom electrode (anode) of the free-burning discharge between metallic molybdenum electrodes. Friable layer of MoO3, which consists of variously oriented transparent prisms and platelets (up to few hundreds of $mu;m in size), was formed by vapor deposition around the electrode. In the second technique, plasma of the underwater electric spark discharges between metal granules was used to obtain stable colloidal solutions with nanoparticles of 20-100 nm sizes.
Properties of Vacuum Arc Influenced by Electrode Diameter and Material in TMF Contact Based on Forced Current Zero
Authors: Huo W. , Wu J. , Deng Y. , Jin X. , Zhu L.
Published: July 2018

With the increase in electrical equipment in More/All Electric Aircraft, 270 V dc power supply systems will be needed. One method for DC interruption is forced current zero (FCZ). Based on FCZ technology with transverse-magnetic-field (TMF) contact, the spiral-type contacts are designed. Experiments with different currents are carried out with contact diameters being 30 mm, 40 mm, and 50 mm, and arcing surface materials Cu-W80 alloy and Cu-Cr50 alloy respectively. It is indicated by the experimental results that breaking capacity of vacuum interrupter and vacuum arc appearance are closely related to the electrode diameter and material. For the same size of electrode diameter, the breaking capacity in Cu-Cr50 is better than that in Cu-W80. With increasing electrode diameter, arc column expansion velocity and diameter increase gradually. Breaking capacity is increasing with larger contact diameter.
Optical Diagnostics of Switching Arcs Near Current-zero: Speckle Imaging and Interferometry
Authors: Stoller P. C. , Carstensen J. , Galletti B. , Doiron C. B. , Sokolov A.
Published: July 2018

Optical diagnostics can be used to obtain spatially resolved measurements of the density, temperature, conductivity, and electron density of circuit breaker arcs embedded in transonic flows; these can be used to validate the results of simulations, the accuracy of which can currently be assessed in only a limited way. We compare speckle imaging and an interferometric approach. Both use a pulsed nanosecond laser. The speckle imaging setup does not require a reference beam, but only yields information about the gradient of the refractive index. Its accuracy is sensitive to the alignment of the optical components. Interferometry directly yields high resolution images of the index of refraction, from which the density can be calculated using the Gladstone-Dale relation. By using two laser beams, interferometry provides spatially resolved information about the electron density. Such measurements are a significant step towards more accurate CFD models.
Influencing Factors on the Dielectric Breakdown Strength in F-gas Free High-voltage Switchgear
Authors: Gossmann S. , Lutz B. , Nikolic P. G.
Published: July 2018

After being in the focus of sciences' and industry's research and development activities for many years, the investigation of possible SF6 gas-alternatives has been even more intensified after the revision of the European regulation on fluorinated gases in 2014. In this contribution the influencing factors on the dielectric breakdown of clean air are investigated for weak inhomogeneous field and gas pressures up to 10 bar. Modelling approaches and experimental data are compared.
Analysis of Radiation Discretization for Modelling a Spark Gap for Surge Currents
Authors: Sander C. , Schmutz J.-E. , Kurrat M.
Published: July 2018

In this paper we address a method for spectrally resolved radiation modelling in thermal plasmas encountered in surge protective devices based on spark gaps. Compared to most switching applications, power input and plasma pressure are much higher which leads to an optically thick plasma with line broadening and enhanced wall ablation. In this situation it is possible to capture the full effect of spectrally resolved radiation on plasma dynamics by performing line-by-line calculations with downsampled absorption spectra. We show that it is possible to achieve radiation convergence with 1000 lines. Approaches for a further reduction of calculation times using band-averaged models and $\kappa$-group models are discussed. The κ-group model is based upon a grouping of the absorption coefficients into subgroups with different ranges of κ before averaging. The spectral calculation results are compared to the approximative methods and significant differences for Rosseland means are observed.
Optimal Band Selection for the Calculation of Planck Mean Absorption Coefficients
Authors: Gnybida M. , Rümpler Ch. , Narayanan V. R. T.
Published: July 2018

Radiative heat transfer is a major heat loss mechanism in thermal plasmas generated during arc flashes/faults in switchgear applications or during high current interruption in low voltage circuit breakers. A common way to calculate the radiation balance is by means of approximate non-gray radiation models like P1 or discrete ordinates (DOM), where the frequency dependent absorption and emission are described in a number of frequency intervals (bands) using a constant absorption coefficient in each band. Current work is focused on finding the optimal number of bands as well as band interval boundaries that provide a reasonable level of accuracy in comparison to a full spectral solution. An optimization procedure has been applied to different SF6 and copper vapor gas mixtures for an assumed temperature profile. Radiation model results using optimized band averaged absorption coefficients as well as spectral values are provided and discussed for the exemplary temperature profile.
Chemical and Electron Interaction Properties of Potential Gaseous Insulation and Arc-quenching Media
Authors: Zhu L. , Tanand D. , Zhao S. , Xiao D.
Published: July 2018

The global warming effects of sulphur hexafluoride (SF6) lead researchers to look for new environmentally-friendly gas media in high-voltage electrical apparatus. The present paper discusses basic chemical and electron interaction properties that brings high insulation strength and good arc interruption capability for a gas. The conclusion shows that gaseous compounds composed of elements in the upright area of periodic table of elements generally have stronger electronegative ability and good electrical properties. And double bond or triple bond in gas molecule can effectively improve the dielectric strength. For gas mixtures, good cooperation of gases will generate synergetic effect, which makes its dielectric strength higher than the weighted average value of each gas. Some aspects in searching for new arc interruption media are also discussed.
Implosive Thermal Plasma Source for Energy Conversion
Authors: Sonsky J , Tesar V. , Gruber J. , Maslani A.
Published: July 2018

Laboratory scale thermal plasma source for magnetohydrodynamic or magnetocumulative generator was developed. The thermal plasma is created from combustible stochiometric mixture of hydrogen and oxygen by spherical implosion of convergent detonation wave. Resulting high velocity plasma is observed by capturing emitted light by hi-speed camera to determine plasma velocity and also spectroscopically in order to estimate of plasma temperatures. Construction of the implosion plasma source is discussed.
Evolution of the Cathode Spot Distribution in an Axial Magnetic Field Controlled Vacuum Arc at Long Contact Gap
Authors: Tezenas du Montcel B. , Chapelle P. , Jardy A. , Creusot C.
Published: July 2018

The distribution of cathode spots in a CuCr25 vacuum arc controlled by an axial magnetic field and ignited on the lateral surface of the cathode is investigated for long gap distances, from the processing of high-speed video images. The processing method includes also estimating the current carried by a single spot and reconstructing the distribution of the current density at the cathode. Various distributions depending partly on the arc current are described.
TSH-secreting pituitary adenoma: late diagnosis and effectiveness of therapy
Authors: Petrik Galina G. , Kosmacheva Elena D. , Polyakova Ulya I. , Butaeva Svetlana V. , Rozhinskaya Ludmila Ya. , Belaya Zhanna E.
Published: July 2018

The modern therapeutic and diagnostic algorithms allow timely detection of pituitary disorder to prescribe adequate treatment. Meanwhile, when interpreting the thyroid status, physicians need to take into account the extremely rare but the actually existing possibility of central thyrotoxicosis. The worldwide practice shows that diagnosis of this condition is rather challenging.
We report a clinical case of a TSH-secreting pituitary adenoma in a 47-year-old female who received a long-term thyrostatic therapy for thyrotoxicosis. The patient was diagnosed with Graves’ disease; however, thyrotoxicosis was actually caused by TSH-oma. The key laboratory signs of central thyrotoxicosis included the combination of episodes of normal or elevated TSH level with the high or normal free T4 level. MRI showed a pituitary macroadenoma. The clinical manifestations of thyrotoxicosis made it possible to rule out the thyroid hormone resistance syndrome. The attempted therapy with octreotide eliminated the clinical and laboratory signs of thyrotoxicosis, so the conservative method was selected as first-line therapy. The features of clinical and laboratory signs, as well as the principles of differential diagnosis and modern methods for treating TSH-secreting pituitary adenomas are discussed.
IDIOPATHIC INFANTILE HYPERCALCEMIA . DESCRIPTION OF CLINICAL CASES AND REVIEW.
Authors: Tikhonovich Yulia V. , Kolodkina Anna A. , Kulikova Kristina S. , Golubkina Yulia Yu. , Kalinchenko Natalia Yu. , Savelieva Larisa V. , Kostik Mikhail M. , Rozhinskaya Ludmila Y. , Tiulpakov Anatoly N.
Published: July 2018

Vitamin D plays a central role in calcium homeostasis. Impaired degradation  of 1,25-dihydroxyvitamin D due to loss-of-function mutations in CYP24A1 leads to significant hypercalcemia, hypercalciuria,  suppressed level of parathyroid hormone (PTH),  nephrocalcinosis and nephrolithiasis.  This condition has been called Idiopathic infantile hypercalcemia.
Treatment includes low calcium diet, rehydration, furosemid,  avoidance of vitamin D supplements  and sun protection.   In severe  cases   glucocorticoids, ketoconazole,  bisphosphonates  and  hemodiafiltration may be used.
Early diagnosis of the disease allows to develop an individual plan for managing these patients to prevent the formation of kidney disease, to conduct a genetic family counseling.
Here, we describe the cohort of  patients (3  children, 2 adults)  with significant hypercalcemia due to  homo- and compound heterozygous mutations in CYP24A1, describe  the main clinical and laboratory characteristics, diagnosis, principles and foundations of the management of patients with this pathology.
Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases
Authors: Tyurenkov Ivan N. , Bakulin Dmitry A. , Kurkin Denis V. , Volotova Elena V.
Published: July 2018

Type 2 diabetes mellitus (DMT2) is a disease significantly increasing the risk of neurodegenerative disorders and stroke. The keen interest in anti-diabetic medications, which can reduce the risk of cardiovascular and neurodegenerative disorders, is caused by the substantial rise in the number of patients with DMT2 as a result of population aging.
According to the clinical trial data, incretin mimetics significantly reduce the glycosylated hemoglobin level, while moderately reducing blood pressure and adipose tissue mass in DMT2patients. When added to the conventional hypoglycemic therapy, analogues of glucagon-like peptide-1 (GLP-1) significantly decrease the risk of cardiovascular complications in DMT2 patients. The positive effect of these medications in patients with neurodegenerative diseases, both the independent and T2DM-associated ones, has been observed. Today, there are ongoing clinical trials of the effect of GLP-1 analogues in patients with Parkinson’s and Alzheimer’s disease.
The available data show that incretin mimetics exhibit neuroprotective properties due to GLP-1 receptors on neurons, microglial and endothelial cells. These receptors were found to be able to trigger the major intracellular signaling pathways that maintain cellular function and inhibit apoptosis under pathological conditions.
In this review, we summarize the results of studies focused on neuroprotective properties of drugs with the incretin-mimetic mechanism of action. The findings on their effect on a number of pathological processes in patients with neurodegenerative diseases and cerebrovascular disturbance are reported. The ability of incretin mimetics to reduce microglial activation, secretion of proinflammatory cytokines and pathological protein aggregation, as well as inhibit neuronal apoptosis, improve mitochondrial functional state, enhance expression of trophic factors and stimulate neurogenesis, is demonstrated.
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a case report
Authors: Khramova Elena B. , Khorosheva Elena Yu. , Perfilova Olga V.
Published: July 2018

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) is an autosomal recessive mitochondrial fatty acid beta-oxidation disorder with variable presentation including lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), hepatic steatosis, and hypocarnitinemia. In this report, we describe a 9-month-old male patient who suffered from recurrent hypoglycemia with hypoglycemic convulsions, vomiting, and neurological regression since the age of 4 months. The patient presented with hypotonia, motor delay, hepatomegaly, protein-energy malnutrition (BMI SDS — 2.8). Biochemical tests demonstrated hypoglycemia (2.5 mmol/l), elevated lactate, creatine phosphokinase, and aminotransferases. There were also increased concentrations of long-chain acylcarnitine and 3-hydroxyacylcarnitine as well as a dramatic decrease in the carnitine level. Digestive tract malformations, endocrinopathies, and degenerative diseases of the nervous system were excluded hydroxyacyl-CoA dehydrogenase (HADHA) gene)testing revealed a homozygous mutation p.Glu474Gln. This confirmed the diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Diet correction by adding medium chain triglycerides, compensation of carnitine deficiency, and symptomatic therapy made it possible to avoid fatal metabolic crises and manage neurological regression. Early detection, diagnosis, and treatment of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency may improve clinical outcomes.
The rare form of congenital adrenal hyperplasia caused by an autosomal dominant form of STAR deficiency
Authors: Kalinchenko Natalia Y. , Chistousova Galina V. , Petrov Vasily M. , Vasiliev Evgeny V. , Tiulpakov Anatoly N.
Published: July 2018

The steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function due to autosomal-recessive mutations in the STAR gene leads to lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids, which causes adrenal insufficiency, primary ovarian failure in 46XX patients, or 46XY disorder of sex development (DSD). However, there were a few reports of 46 XY DSD patients with LCAH caused by a heterozygous mutation in the STAR gene. Here, we describe another rare case of LCAH in a 46XY patient with DSD and primary adrenal insufficiency due to an autosomal-dominant mutation in the STAR gene.
Molecular genetic factors in the development of papillary thyroid cancer in the Kazakh population
Authors: Espenbetova Mayra Zhaksimanovna , Glushkova Natalya Egorovna , Krykpayeva Ainur Serikovna
Published: July 2018

Introduction. In the last decade several population studies on the association of the genes NKX2-1 and FOXE1 with sporadic papillary thyroid cancer were conducted. In the Kazakh population of similar work to date were not conducted. The aim of this study was to study the genetic association of the FOXE1 (rs9655313) and NKX2-1 (rs944289) oncomarkers with papillary thyroid cancer in the Kazakh population.
Materials and methods. We conducted a case-control study that allows us to retrospectively evaluate the association of NKX2-1 and FOXE1 genes and papillary thyroid cancer.
Results. The frequency distribution of FOXE1 rs965513 polymorphism in the group of papillary thyroid cancer and the control group detected by healthy individuals was significantly different (χ2 = 100.09, D.f. = 2, p = 0.000). In the group of cases, the AA genotype (17.5%) was in three times more often compared with the control group (5.1%). The GG variant had a lower frequency in the group of persons of papillary thyroid cancer (37.9%) against the control group (61.4%), the odds ratio (OR) in the FOXE1 rs965513 group was 2.367. The distribution of the NKX2-1 (rs944289) polymorphism frequencies in the compared groups of values were significantly different (χ2 = 100.09, D.f. = 2, p = 0.000). In the group of cases, the genotype of TT (30.5%) against the control group (20.7%) was 1.5 times more common. The SS variant had a lower frequency of occurrence in the group of persons of papillary thyroid cancer (19.8%) against the control group (28.9%), OR in NKX2-1 (rs944289) group was 1.46.
Conclusion. Carrying out screening for carriers of FOXE1 rs965513 and NKX2-1 (rs944289) can become an effective means of early diagnosis with a high frequency of its spread and associations with cases of papillary thyroid cancer in the Kazakh population.
Glucokinase activators — a promising class of antidiabetic drugs
Authors: Spasov Alexander A. , Kosolapov Vadim A. , Babkov Denis A. , Mayka Olga Yu.
Published: July 2018

Type 2 diabetes mellitus is an urgent problem of the modern healthcare. Despite a wide choice of oral hypoglycemic drugs, today there is a great need to create and introduce into clinical practice new, effective, and safe drugs for the treatment of diabetes. One of the promising targets for the creation of new antidiabetics is a glucokinase. It has an exceptionally high influence on glucose homeostasis, serving as a glucose “sensor” in pancreatic β-cells and controlling the rate of glycogen synthesis in the liver. In the present work, the molecular-genetic structure of the enzyme, as well as its interrelation with the organs and tissues of the organism, is presented. The modern ideas about activators of glucokinase as a promising class of antidiabetic drugs are outlined, their hypoglycemic and general antidiabetic effects proved in preclinical and clinical studies are considered. The most advanced activators of glucokinase, undergoing clinical trials, are indicated.
Influence of female hormones on the P-glycoprotein functioning
Authors: Shchulkin Alexey V. , Chernykh Ivan V. , Mylnikov Pavel Yu. , Utkin Dmitry O. , Yakusheva Elena N.
Published: July 2018

The P-glycoprotein (Pgp, ABCB1-protein) is a transport protein localized in the membrane of hepatocytes, small and large intestine enterocytes, renal tubular epitheliocytes, endothelial cells of histohematic barriers, and tumor cells.
Aim — to study the effect of estradiol and progesterone physiological concentrations on the Pgp functional activity on the whole body.
Material and methods. The work was performed on 17 adult female chinchilla rabbits. The first group of rabbits underwent a “false operation” (n=5); the second group (n=6) underwent ovariectomy. The third group (n=6) was ovariectomized and received estradiol (0.5 mg/rabbit) for 14 days (starting on the 14th postoperative day), followed by combined administration of estradiol (0.5 mg/rabbit) and progesterone (5 mg/rabbit) for 14 days. The Pgp functional activity was determined in rabbits of all groups using HPLC analysis of fexofenadine pharmacokinetics on day 7 before the study onset and on day 14, 28, and 42 after the operation. Accumulation of fexofenadine in rabbits indicates Pgp inhibition, and a decrease in its content means Pgp induction.
Results. Ovariectomy led to a decrease in the Pgp functional activity. The estradiol introduction for 14 days after ovariectomy did not significantly affect the transport protein functional activity. Combined administration of estradiol and progesterone for 14 days resulted in an increase in the Pgp activity, compared to that in the ovariectomy series and baseline values.
Conclusions. The dependence of the transport protein activity on the dynamics of physiological estradiol and progesterone concentrations suggests that the effectiveness of pharmacotherapy with Pgp substrates may depend on the menstrual cycle phase, and drug dose correction may be used to increase the pharmacotherapy effectiveness.
Atypical parathyroid adenoma with clinically aggressive course of hyperparathyroidism: clinical case report
Authors: Mokrysheva Natalia G. , Eremkina Anna K. , Slashchuk Konstantin U. , Bespalov Alexey I. , Voronkova Iya А. , Rumyantsev Pavel O. , Degtyarev Mikhail V. , Kuznetzov Nikolay S. , Latkina Nonna V.
Published: July 2018

Primary hyperparathyroidism is common clinical endocrine disorder with a prevalence between 1–2%. Solitary parathyroid adenomas account from 80 to 85% of cases of PHPT, hyperplasia and multiple adenomas is up to 15%, parathyroid carcinoma is a very rare cause of PHPT, accounting for about a 1% of cases. Clinically aggressive and atypical adenomas should be separately noted because of severe clinical course and life-threatening hypercalcemia, high morbidity and mortality, unknown malignant potential. No definite criteria are considered to be present to distinguish preoperatively atypical adenoma from parathyroid typical adenoma or carcinoma. The clinical course of the disease remains the only tool that allows to suspect an aggressive tumor on the preoperative stage. We present the clinical case of a 61-year-old female patient with a clinically “aggressive” course of PHPT and severe metabolic disturbances of bone tissue due to the atypical adenoma of the parathyroid gland.
Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology
Authors: Rumyantsev Pavel O. , Yazykova Diana R. , Slashchuk Konstantin Y. , Degtyarev Mikhail V. , Yasyuchenya Valentina S. , Serzhenko Sergey S. , Sheremeta Marina S. , Dedov Ivan I.
Published: July 2018

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumours, up to 40% of which occur in the setting of a hereditary syndrome. The incidence is 2 to 8 per million persons per year. The peak incidence occurs in the third to fifth decades of life. According to the most recent classification, chromaffin tumours refer to malignant neoplasms. The incidence of metastasis in pheochromocytomas is 10%; in paragangliomas it is 25%. Clinical manifestations of PPGLs are caused by the excess of catecholamines. More than 20 hereditary gene mutations are known to result in PPGLs development. According to the molecular and cellular pathophysiology, all currently known mutations can be divided into 2 groups: the first group – SDHх, SDHAF2 (the assembly factor of SDH, FH, MDH2) – disrupts the Krebs cycle and mitochondrial energy transport chain; the second group – RET, NF1, TMEM127, MAX – leads to mutations in receptor protein kinases (tyrosine kinase), activating intracellular signal pathways (PI3K-AKT-mTOR and MYC), which are responsible for cell growth, growth regulation and cell differentiation. As a result, HIF transcription factors are stabilized (oxidative stress), and DNA methylation is changed, which leads to severe disturbances in gene expression and to malignant transformations of cells. There are three main biochemical phenotypes of PPGLs: noradrenergic, adrenergic and dopaminergic. According to the tumor type, the patient’s age and family history, complementary genetic testing and molecular visualization are recommended. In clinical practice, the biochemical tumor phenotype, its stage, family history and especially the genetic tumor “passport” allow to choose the best molecular visualization method (SPECT-CT/PET-CT) to personalize treatment and prognosis.
Unverricht-Lundborg disease in an adult female patient: a clinical case
Authors: Karlov V. A. , Zhidkova I. A. , Mishina E. Yu. , Vlasov P. N. , Margosyuk N. V. , Tingaeva L. P. , Perepelova E. M. , Perepelov V. A. , Gladov B. P. , Trukhanov S. A.
Published: July 2018

We have considered it appropriate to publish this case due to the rarity of progressive myoclonus epilepsy; diagnostic difficulties, particularly in the early stages of the disease (the female patient has been long followed up for diagnosed juvenile myoclonic epilepsy); the relative role of a genetic study because it has not brought results in this case, and,  finally, a problem with therapy, and a significant contribution to the  achievement of certain success of currently available antiepileptic drugs, levetiracetam in particular.
Juvenile myoclonic epilepsy: neurophysiological aspects
Authors: Shilkina O. S. , Shnaider N. A. , Dmitrenko D. V. , Kim K. T.
Published: July 2018

The review presents an update on the electroencephalographic characteristics and neurophysiology of juvenile myoclonic epilepsy (JME) in Russia and foreign countries.

Materials and methods.The authors have performed a literary search for the full-text publications on JME electroencephalography and neurophysiology worldwide and in the Russian Federation, which are available in Russian and foreign databases.

Results and discussion. Analysis of the literature suggests that JME patients have some electroencephalographic pattern features that include the atypical morphology of spike-and-slow-wave  complexes, as well as amplitude asymmetry, focal discharges, focal  onset of paroxysms, focal paroxysmal shift, and generalized paroxysmal fast rhythm.The analysis of the literature also indicates that primary care neurologists, clinical neurophysiologists, and epileptologists should be informed about the electroencephalographic characteristics of JME to timely diagnose the disease and to rule out the use of inadequate therapy.
Magnetic resonance spectroscopy of the brain in the diagnosis of temporal lobe epilepsy
Authors: Solomatova E. S. , Shnaider N. A. , Molgachev A. A. , Dmitrenko D. V. , Strotskaya I. G.
Published: July 2018

The temporal lobe is the most epileptogenic region of the brain. 90% of patients with temporal ictal epileptomorphic EEG activity have a variable long history of seizures. Magnetic resonance spectroscopy  (MRS) may be useful in identifying an epileptogenic focus in patients  with epilepsy without apparent structural pathology at neuroimaging.

Objective: to systematize the results of early studies on this issue.

Materials and methods.An electronic search was carried out in two English-language (Medline, PubMed) and one Russian-language (eLIBRARY.RU) databases. The search queries found  18,019 citations, by which 12 full-text articles were selected.

Results and discussion.The main criteria for the diagnosis of temporal lobe epilepsy by MRS is to lower the level of N-acetylaspartate (NAA), the ratio of NAA to creatinine + choline  (NAA/(Cr + Cho) in the brain region where there is neuronal death  or damage, as well as a change in the level of myo-inositol, the  elevated level of which indicates the presence of an epileptogenic  focus, while the decreased one shows the spread of pathological activity to the adjacent tissues.

Conclusion.This review will contribute to a better diagnosis of temporal lobe epilepsy, as well as to the intravital noninvasive detection of metabolic changes in the brain long before the development of structural pathology.
A clinical case of SYNGAP1-associated encephalopathy in a girl with epilepsy, intellectual disability, and autism
Authors: Savelieva N. N. , Yakunina A. V. , Poverennova I. E.
Published: July 2018

This paper describes a female patient aged 3 years 6 months with SYNGAP1-associated encephalopathy manifesting with symptomatic epilepsy, intellectual disability, and autism. There were difficulties in  differential diagnosis, since in addition to SYNGAP1 mutation (c2214_2217deltgag), heterozygous BCKDHB gene mutation  (chr6: 80910740G>a, rs3834233) and microduplication of a segment of chromosome 22 were found de novo. The features of the course and  treatment of epilepsy in SYNGAP1 are discussed. A combination of  valproic acid and oxcarbazepine was the most effective treatment for epilepsy.
Model Grey (1,1) dan Grey-Markov pada Peramalan Realisasi Penerimaan Negara
Authors: Ahdika Atina
Published: July 2018

Setiap Negara memerlukan sumber penerimaan untuk mewujudkan pembangunan nasional dan membiayai segala keperluannya. Di Indonesia, terdapat tiga sumber utama penerimaan Negara; penerimaan pajak, penerimaan bukan pajak, serta penerimaan hibah baik dari dalam maupun luar negeri. Untuk mengantisipasi berbagai keperluan serta mengoptimalkan penggunaan penerimaan Negara, maka perlu adanya proyeksi realisasi penerimaan Negara dari ketiga sumber tersebut. Proyeksi tersebut dapat dilakukan dengan menggunakan model deret waktu klasik baik model deterministik maupun model stokastik. Namun demikian, pada model deret waktu klasik terdapat beberapa asumsi yang harus dipenuhi seperti pola data atau jumlah minimal data. Sebagai alternatif, pada penelitian ini akan dilakukan peramalan dengan menggunakan model Grey (1,1) dan Grey-Markov; perpaduan antara model Grey dengan analisis Rantai Markov. Model ini memiliki keunggulan dibandingkan model deret waktu klasik, yaitu tidak perlu adanya asumsi mengenai pola data serta peramalan dapat dilakukan meskipun data yang dimiliki cukup kecil (minimal 4 data). Hasil analisis menunjukkan bahwa model Grey-Markov secara umum memberikan akurasi peramalan yang lebih baik dibandingkan dengan model Grey (1,1).

[Every state requires a source of revenue to realize its national development and fund its needs. In Indonesia, there are three main sources of state revenues; tax, non-tax, and grant revenues both from within and outside the country. To anticipate various purposes and optimize the use of state revenues, it is necessary to project the realization of the revenues from these three sources. The projection can be done using a classical time series model in both deterministic and stochastic models. However, in the classical time series model there are several assumptions that must be met such as data patterns or minimal amount of data. Alternatively, in this study the data will be forecasted using Grey (1,1) model and Grey-Markov model; a combination of the Grey model with Markov Chain analysis. This models have advantages over the classical time series models, ie no need for assumption about data pattern and forecasting can be done even though there are small size data (at least 4 data). The results of the analysis show that generally Grey-Markov model provides better forecasting accuracy compared with Grey (1,1) model.]