bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monte-Carlo simulation of clinical and economic effectiveness of drugs (on example of antibiotics therapy of acute bronchitis with bronchospasm in children)
Authors: Zhukova Olga V. 
Published: September 2019

Introduction: The study objective was to determine which antibiotics are optimal in the treatment of children with complicated acute bronchitis with bronchospasm. For that, a Monte-Carlo simulation was conducted.
Materials and methods: The retrospective study was performed on the antibiotic therapy data from 1604 medical records of inpatients from Nizhny Novgorod (Russian Federation) medical centers admitted with acute bronchitis with bronchospasm. The treatment programs involved cephalosporins, inhibitor-protected penicillins, and macrolides. The starter drug was selected empirically considering the possible etiology and sensitivity of the presumed pathogen to the antimicrobial agents. The input data for the model (Monte-Carlo simulation) were the costs of antibiotic therapy and the probability of the clinical outcome (recovery, or the absence of effect). The probabilities of the clinical outcome were described with β-distribution, while the costs distribution was described using gamma-distribution.
Results and discussion: Most positive clinical outcomes were observed with the use of macrolides, which also provided the lowest CER (cost-efficiency ratio), and are, therefore, optimal pharmacoeconomically. During the trial, the confidence intervals were evaluated for the clinical efficiency (95% CI of the β-distribution curve). The least interval of probable clinical efficiency for the investigated nosology was found for macrolides, which indicates their high clinical efficiency.
Conclusion: Monte-Carlo method visualizes the results of clinical-economical evaluation of any medical technology in one disease compared to another. That is of value for the clinical pharmacologists and health professionals selecting the drugs for healthcare facilities.
Pharmacological correction of morphofunctional retinal injury using 11-amino acid fragment of darbepoetin in the experiment
Authors: Gubareva Victoria O. , Pazhinsky Anton L. , Lugovskoy Sergey S. , Dubovtsova Elizaveta Yu. , Vain Daria S. , Pobeda Anna S. , Pasenov Konstantin N. 
Published: September 2019

Introduction: The retinoprotective effect of the 11-amino acid fragment of darbepoetin PRK-002 on the models of hypertensive retinal angiopathy and hypertensive neuroretinopathy in Wistar rats was investigated in comparison with carbamylated darbepoetin and sulodexide.
Materials and methods: The protective effects of the pharmacological agents were assessed using the following criteria: a semi-quantitative assessment of changes in the eye fundus when performing ophthalmoscopy, the retinal blood flow, the b/a coefficient, eNOs expression in retinal vessels, specific number of neuronal nuclei in the inner nuclear layer, and p53 expression in the retina.
Results and discussion: A pronounced protective effect, exceeding sulodexide at a dose of 150 LRU/kg and carbamylated darbepoetin at a dose of 300 μg/kg when correcting retinal angiopathy was observed in PRK-002 at a dose of 4 µg/kg, which expressed in adjustment of the retinal vessels’ calibers, removing retinal arterio-venous crossings, reaching the target levels of the retinal microcirculation, the b/a coefficient, and the restoration of eNOs expression in the endothelium of retinal vessels. PRK-002 at a dose of 4 µg/kg has a pronounced neuroprotective effect comparable to carbamylated darbepoetin at a dose of 300 µg/kg in correction of hypertensive neuroretinopathy, which expressed in the normalization of the fundus image, reaching the b/a target values, the specific number of neuronal nuclei in the inner nuclear layer, inhibition of p53 expression in the neurons of the inner nuclear and ganglionic layers.
Conclusion: The study revealed angio- and neuroprotective activity of the 11-amino acid fragment of darbepoetin PRK-002 in correction of retinal injury formed on the background of hypertension.
Complex assessment of blood pressure regulation system in hypertension patients
Authors: Samorodskaya Natalya A. , Polischuk Lily V. , Eliseeva Ludmila N. 
Published: September 2019

Introduction: There are almost no studies characterizing the integrative level of blood pressure (BP) regulation.
Materials and methods: 277 people of both genders aged 58.6±6.4 with stage II hypertension disease were randomized into six groups. The monotherapy of hypertension disease was conducted in five groups, using nebivolol, lisinopril, indapamide, amlodipine, and losartan. The sixth group had a combined therapy (lisinopril/indapamide). The therapy effectiveness was assessed at four levels of blood pressure regulation, using the following methods: 1) laser Doppler flowmetry, determination of the level of tumor necrosis factor-α and interleukin-10; 2) echocardiography and Doppler sonography, ultrasound examination of the renal blood flow, ECG, Holter monitoring of ECG; 3) an examination of the heart rate variability level and a quantitative assessment of beta-adrenoreception of erythrocyte cell membranes; 4) the regulatory and adaptive status was assessed, using the method of cardio-respiratory synchronism.
Results and discussion: A more significant BP decrease was revealed during a combination therapy (by 20.4% of the baseline daily value). At the integrative level, an index of the regulatory and adaptive status (iRAS) increased in the treatment with lisinopril/indapamide combination (by 40.5%), amlodipine (by 40.5%), losartan (by 35.3%), and lisinopril (by 30.2%). Nebivolol administration resulted in a 13.5% decrease in iRAS. Indapamide therapy had no significant effect on iRAS.
Conclusion: A comprehensive assessment of the blood pressure regulation system makes it possible to control the effectiveness of the therapy not only on a target organ or function, but also on the condition of the organism as an integral system.
Combined use of arginase II inhibitors and tadalafil for the correction of monocrotaline pulmonary hypertension
Authors: Koklin Ivan S. , Danilenko Lyudmila M. 
Published: September 2019

Introduction: The concept of the regulatory role of endothelium in the pathogenesis of pulmonary hypertension (PH) is fundamental. Research objective: To study the protective effects of the selective arginase II inhibitors L207-0525 and L327-0346 in combination with tadalafil in a monocrotaline model of pulmonary hypertension in rats.
Materials and methods: Monocrotaline-induced pulmonary hypertension was simulated in 10 animals by a subcutaneous injection of an alcohol-water solution of monocrotaline (MCT) in the dose of 60 mg/kg. Seven days after the injection of MCT, the administration of L207-0525 and L327-0346 in the doses of 1 mg/kg and 3 mg/kg was started. The compounds were administered intragastrically once a day for 21 days.
Results and discussion: It was found that L207-0525 and L327-0346 in the dose of 3 mg/kg and tadalafil in the dose of 1 mg/kg prevented the development of pulmonary hypertension, which was expressed in a statistically significant decrease in the coefficient of endothelial dysfunction (CED, prevention of an increase in systolic pressure in the right ventricle, as well as Fulton, RV/BW and WT indices. The greatest activity was shown by L207-0525 and L327-0346 in the dose of 3 mg/kg in combination with tadalafil in the dose of 0.1 mg/kg.
Conclusions: The received results suggest the dose-dependent protective activity of selective arginase II inhibitors L207-0525 and L327-0346 and the development of the additive effect of their combined use with low doses of PDE-5 inhibitor tadalafil in relation to the development of monocrotaline pulmonary hypertension
Treatment Options for Osteoarthritis
Authors: Snibbe Jason C , Gambardella Ralph A 
Published: September 2019

abstract
Osteoarthritis is the most common form of arthritis and can be a major source of disability. Many older patients continue to be active in sportsrelated activities. Therefore, treating an active patient with osteoarthritis is becoming more common. Physical therapy and weight loss continue to play a central role in the treatment of patients with osteoarthritis. Nonsteroidal anti-inflammatory drugs decrease inflammation and swelling, which makes physical therapy more effective. Intra-articular corticosteroids have been used for the treatment of osteoarthritis. However, no guidelines exist for the administration of corticosteroids and they can be associated with increased risk of tendon rupture and infection. Viscosupplementation has gained popularity in the treatment of osteoarthritis of the knee. Intra-articular injections of hyaluronic acid have been shown to decrease pain and improve functional outcomes.
TNF-α Contributes to Lymphoid Tissue Disorganization and Germinal Center B Cell Suppression during Intracellular Bacterial Infection
Authors: Popescu Maria , Cabrera-Martinez Berenice , Winslow Gary M. 
Published: September 2019

Abstract
Bacterial, parasitic, and viral infections are well-known causes of lymphoid tissue disorganization, although the factors, both host and/or pathogen derived, that mediate these changes are largely unknown. Ehrlichia muris infection in mice causes a loss of germinal center (GC) B cells that is accompanied by the generation of extrafollicular T-bet+ CD11c+ plasmablasts and IgM memory B cells. We addressed a possible role for TNF-α in this process because this cytokine has been shown to regulate GC development. Ablation of TNF-α during infection resulted in an 8-fold expansion of GL7+ CD38lo CD95+ GC B cells, and a 2.5- and 5-fold expansion of CD138+ plasmablasts and T-bet+ memory cells, respectively. These changes were accompanied by a reduction in splenomegaly, more organized T and B cell zones, and an improved response to Ag challenge. CXCL13, the ligand for CXCR5, was detected at 6-fold higher levels following infection but was much reduced following TNF-α ablation, suggesting that CXCL13 dysregulation also contributes to loss of lymphoid tissue organization. T follicular helper cells, which also underwent expansion in infected TNF-α­–deficient mice, may also have contributed to the expansion of T-bet+ B cells, as the latter are known to require T cell help. Our findings contrast with previously described roles for TNF-α in GCs and reveal how host–pathogen interactions can induce profound changes in cytokine and chemokine production that can alter lymphoid tissue organization, GC B cell development, and extrafollicular T-bet+ B cell generation.
Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial infarction
Authors: Pandey Chandra Prakash , Misra Ankita , Negi Mahendra Pal Singh , Kanuri Babu Nageswararao , Chhonker Yashpal Singh , Bhatta Rabi Shanker , Narain Varun Shanker , Dikshit Madhu 
Published: September 2019

Background & objectives:
Cytochrome P450, P2Y12, cyclooxygenase-1 (COX1) and glycoprotein V1 (GPVI) gene polymorphisms are known to affect patient responsiveness towards aspirin and clopidogrel dual antiplatelet therapy (DAPT). The present study was undertaken to identify aspirin and clopidogrel non-responsiveness and its association with genetic polymorphism in patients with myocardial infarction (MI).

Methods:
A total of 207 MI patients who were on DAPT, were included. The DAPT non-responsiveness was determined by light transmittance aggregometry using arachidonic acid and adenosine diphosphate and high platelet reactivity by collagen. Platelet activation biomarkers, thromboxane B2 (TxB2) and soluble CD40 ligand (sCD40L) were measured in plasma. Patient compliance was checked by estimating drug and its metabolite levels (aspirin and clopidogrel) in plasma using liquid chromatography-mass spectrometry/mass spectrometry. Genomic DNA was extracted, amplified by polymerase chain reaction and subsequently sequenced to identify CYP450, P2Y12, COX1 and GPVI gene polymorphisms.

Results:
Of the 207 patients, 32 were non-responders. The DAPT non-responsiveness was found in 15.5 per cent patients. The non-responsiveness showed a significant and an independent association with gender [odds ratio (OR)=0.18, 95% confidence interval (CI)=0.01-0.78, P=0.023], TxB2 (OR=1.00, 95% CI=1.00-1.01, P=0.013), CYP2C19*2 G>A (OR=3.33, 95% CI=1.04-10.69, P=0.044) and GPVI T>C (OR=0.23, 95% CI=0.08-0.67, P=0.007) after adjusting the demographic, clinical and genetic confounding factors when assessed between non-responder and responder compliant patients.

Interpretation & conclusions:
The study showed a significant association of genetic polymorphisms (CYP2C19*2 G>A and GPVI T>C) with DAPT non-responsiveness in MI patients. The findings of this study need further validation in a large cohort of patients with clinical follow up.
Benchmarking the predictive capability of hydrological models for river flow and flood peak predictions across over 1000 catchments in Great Britain
Authors: Lane Rosanna A. , Coxon Gemma , Freer Jim E. , Wagener Thorsten , Johnes Penny J. , Bloomfield John P. , Greene Sheila , Macleod Christopher J. A. , Reaney Sim M. 
Published: September 2019

Abstract. Benchmarking model performance across large samples of
catchments is useful to guide model selection and future model development.
Given uncertainties in the observational data we use to drive and evaluate
hydrological models, and uncertainties in the structure and parameterisation
of models we use to produce hydrological simulations and predictions, it is
essential that model evaluation is undertaken within an uncertainty analysis
framework. Here, we benchmark the capability of several lumped hydrological
models across Great Britain by focusing on daily flow and peak flow
simulation. Four hydrological model structures from the Framework for
Understanding Structural Errors (FUSE) were applied to over 1000 catchments
in England, Wales and Scotland. Model performance was then evaluated using
standard performance metrics for daily flows and novel performance metrics
for peak flows considering parameter uncertainty. Our results show that lumped hydrological models were able to produce
adequate simulations across most of Great Britain, with each model producing
simulations exceeding a 0.5 Nash–Sutcliffe efficiency for at least 80 % of
catchments. All four models showed a similar spatial pattern of performance,
producing better simulations in the wetter catchments to the west and poor
model performance in central Scotland and south-eastern England. Poor model performance
was often linked to the catchment water balance, with models unable to
capture the catchment hydrology where the water balance did not close.
Overall, performance was similar between model structures, but different
models performed better for different catchment characteristics and metrics,
as well as for assessing daily or peak flows, leading to the ensemble of
model structures outperforming any single structure, thus demonstrating the
value of using multi-model structures across a large sample of different
catchment behaviours. This research evaluates what conceptual lumped models can achieve as a
performance benchmark and provides interesting insights into where
and why these simple models may fail. The large number of river catchments
included in this study makes it an appropriate benchmark for any future
developments of a national model of Great Britain.
Does the weighting of climate simulations result in a better quantification of hydrological impacts?
Authors: Wang Hui-Min , Chen Jie , Xu Chong-Yu , Chen Hua , Guo Shenglian , Xie Ping , Li Xiangquan 
Published: September 2019

Abstract. With the increase in the number of available global climate models (GCMs), pragmatic questions come up in using them to quantify climate change impacts on hydrology: is it necessary to unequally weight GCM outputs in the impact studies, and if so, how should they be weighted? Some weighting
methods have been proposed based on the performances of GCM simulations with respect to reproducing the observed climate. However, the process from
climate variables to hydrological responses is nonlinear, and thus the
assigned weights based on performances of GCMs in climate simulations may
not be correctly translated to hydrological responses. Assigning weights to
GCM outputs based on their ability to represent hydrological simulations is
more straightforward. Accordingly, the present study assigns weights to GCM
simulations based on their ability to reproduce hydrological characteristics
and investigates their influences on the quantification of hydrological
impacts. Specifically, eight weighting schemes are used to determine the
weights of GCM simulations based on streamflow series simulated by a lumped
hydrological model using raw or bias-corrected GCM outputs. The impacts of
weighting GCM simulations are investigated in terms of reproducing the
observed hydrological regimes for the reference period (1970–1999) and
quantifying the uncertainty of hydrological changes for the future period (2070–2099). The results show that when using raw GCM outputs to simulate streamflows, streamflow-based weights have a better performance in
reproducing observed mean hydrograph than climate-variable-based weights.
However, when bias correction is applied to GCM simulations before driving
the hydrological model, the streamflow-based unequal weights do not bring
significant differences in the multi-model ensemble mean and uncertainty of
hydrological impacts, since bias-corrected climate simulations become rather
close to observations. Thus, it is likely that using bias correction and
equal weighting is viable and sufficient for hydrological impact studies.
O protagonismo indígena nas aulas de História: problemas e desafios no livro didático.
Authors: Rosa Francis Mary Soares Correia da 
Published: September 2019

Objetivamos nesse artigo um estudo ensaístico das possibilidades de implementação da lei 11.645/08 no que se refere à temática indígena nas aulas de história da educação básica, por meio de um estudo crítico ao livro didático de história e das categorias de análise presente na história indígena, a saber, resistência e do protagonismo. A escolha pelo conceito do protagonismo e resistência indígena como fio condutor surge diante de uma dupla necessidade enquanto professora, historiadora e filósofa: o primeiro passo é construir um viés crítico à imagem dos povos indígenas em um dos livros didáticos de história aprovados no último PNLD/História-2018, historicizando às categorias de análise costumeiramente apresentadas e, o segundo passo: estabelecer subsídios para se pensar criticamente a produção de um “vazio” discursivo no que se refere ao protagonismo e os movimentos de luta e resistência indígenas. Por meio de uma revisão bibliográfica crítica e relacional ao tema, optou-se por uma abordagem ensaística, porém fundamentada em uma revisão da literatura que aponta como principal suporte os estudos de Grupioni (2004), Munduruku (2009; 2012) e Santos e Felippe (2017), dentro outros. Espera-se contribuir para a ampliação sobre as discussões da implementação da lei 11.645/08 e o livro didático de história, assim como apontar subsídios para o ensino de história comprometido com essa demanda legal.
Quilombo, identidade e educação escolar: o ensino de História na escola David Miranda em Santana-Amapá
Authors: Custódio Elivaldo Serrão , Foster Eugénia da Luz Silva , Souza Silvaney Rubens Alves de 
Published: September 2019

O presente artigo objetiva discutir sobre quilombo, identidade e educação escolar: o ensino de história na escola David Miranda localizada no município de Santana, estado do Amapá. Trata-se de um estudo exploratório de abordagem qualitativa que utilizou da pesquisa bibliográfica, a análise documental, a observação direta e a entrevista como forma de investigação. O trabalho analisou um projeto pedagógico da referida escola chamado “Identidade Cultural”, cuja essência representa uma interessante experiência de ação pedagógica, onde saberes da comunidade local em conjunto com uma sensibilidade dos educadores, produziu um diálogo entre o passado e o presente que contribuiu para fortalecer a identidade de uma comunidade que anseia pelos seus direitos e busca resguardar a sua propriedade e sua memória cultural. Os resultados da pesquisa revelam que a experiência ocorrida na escola local demonstra que ainda há um longo caminho a ser trilhado na busca de uma educação quilombola efetiva no estado do Amapá, mas os agentes sociais que fazem a escola, estão se esforçando na árdua tarefa de construir uma educação adequada aos novos anseios da comunidade local.
Interbuilding pounding damage observed in the 2010 Darfield earthquake
Authors: Cole Gregory , Dhakal Rajesh , Carr Athol , Bull Des 
Published: September 2019

Five days after the Darfield earthquake, a street survey of buildings with pounding damage was performed in Christchurch Central Business District (CBD). Pounding damage did not occur very often, and the level of damage observed was generally low. Moderate to severe pounding damage was observed only in some unreinforced masonry buildings. Outside the CBD one collapsed storey can be attributed to pounding.
The majority of pounding damage occurred in vertical structural elements. Adjacent stepped façades were also found to be susceptible. The damage patterns associated with pounding could have led to building collapse in more severe/longer duration shaking or major aftershocks. Pounding damage remains a serious concern for future strong earthquakes in New Zealand.
What do we mean by the directions “cranial” and “caudal” on a vertebra?
Authors: Taylor Michael P , Wedel Matthew J 
Published: September 2019

In illustrating vertebrae, it is important to consistently depict their orientation, so we can objectively assess and compare the slope of the neural arch, neural canal, or articular surfaces. However, differing vertebral shapes across taxa and across regions of the spinal column make it difficult to maintain consistency, or even define what we mean by the directions “cranial” and “caudal”. Consequently, characters such as “Neural arch slopes cranially 30° relative to the vertical” are disputable rather than objective measurements. Cranial and caudal are defined as directed along the horizontal axis, but several different notions of “horizontal” are possible:
1. Long axis of centrum is horizontal. This is appealing for elongate vertebrae such as sauropod cervicals, but is not always well defined, and is difficult to determine for craniocaudally short vertebrae such as most caudals.
2. Articular surfaces of centrum are vertical. Difficult to determine when dealing with facets that are concave or (worse) convex; and ambiguous for “keystoned” vertebrae in which the facets are not parallel.
3. Neural canal is horizontal. Anatomically informative, but difficult to determine in vertebrae that have not been fully prepared or CT-scanned, and impossible to see in lateral view. Ambiguous for vertebrae where the dorsal and ventral margins of the canal are not straight or not parallel.
4. Similarity in articulation (“horizontal” is defined as a line joining the same point on two similarly oriented copies of the same vertebra when optimally articulated). This is less intuitive than definitions 1–3, but takes the entire vertebra into account.
We advocate explicitly stating a definition and using it consistently. In most cases, definition 3 (“Neural canal is horizontal”) best reflects anatomical and developmental realities, and it is therefore preferred. Low-tech techniques can be used to determine neural canal orientation with adequate precision for most purposes.