bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid clinical mutational testing ofKRAS,BRAFandEGFR: a prospective comparative analysis of the Idylla technique with high-throughput next-generation sequencing
Authors: Van Haele Matthias , Vander Borght Sara , Ceulemans An , Wieërs Michiel , Metsu Sofie , Sagaert Xavier , Weynand Birgit 
Published: July 2019

AimsPrecision medicine therapy is remodelling the diagnostic landscape of cancer. The success of these new therapies is often based on the presence or absence of a specific mutation in a tumour. The Idylla platform is designed to determine the mutational status of a tumour as quickly and accurately as possible, as a rapid, accurate diagnosis is of the utmost importance for the treatment of patients. This is the first complete prospective study to investigate the robustness of the Idylla platform forEGFR,KRASandBRAFmutations in non-small cell lung cancer, metastatic colorectal cancer and metastatic melanoma, respectively.MethodsWe compared prospectively the Idylla platform with the results we obtained from parallel high-throughput next-generation sequencing, which is the current gold standard for mutational testing. Furthermore, we evaluated the benefits and disadvantages of the Idylla platform in clinical practice. Additionally, we reviewed all the published Idylla performance articles.ResultsThere was an overall agreement of 100%, 94% and 94% between the next-generation panel and the IdyllaBRAF,KRASandEGFRmutation test. Two interesting discordant findings among 48 cases were observed and will be discussed together with the advantages and shortcoming of both techniques.ConclusionOur observations demonstrate that the Idylla cartridge for theEGFR,KRASandBRAFmutations is highly accurate, rapid and has a limited hands-on time compared with next-generation sequencing.
Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia
Authors: Fernandez Hubert H. , Stamler David , Davis Mat D. , Factor Stewart A. , Hauser Robert A. , Jimenez-Shahed Joohi , Ondo William G. , Jarskog L. Fredrik , Woods Scott W. , Bega Danny , LeDoux Mark S. , Shprecher David R. , Anderson Karen E. 
Published: July 2019

ObjectiveTo evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD).MethodPatients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as ‘Much Improved’ or ‘Very Much Improved’ on the Clinical Global Impression of Change.ResultsA total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was –4.9 (0.4) at Week 54 (n = 146), – 6.3 (0.7) at Week 80 (n = 66) and –5.1 (2.0) at Week 106 (n = 8).ConclusionsOverall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD.Trial registration numberNCT02198794.
Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial
Authors: Jia Jingya , Hu Jing , Huo Xiaoxu , Miao Rujuan , Zhang Yanping , Ma Fei 
Published: July 2019

ObjectiveOur study aimed to assess the effect of a 12-month vitamin D supplementation on cognitive function and amyloid beta (Aβ)-related biomarkers in subjects with Alzheimer’s disease (AD).Methods This was a randomised, double-blind, placebo-controlled trial. 210 AD patients were randomly divided into intervention and control groups. Participants received 12-month 800 IU/day of vitamin D or starch granules as placebo. Tests of cognitive performance and Aβ-related biomarkers were measured at baseline, 6 months and 12 months.Results Repeated-measures analysis of variance showed significant improvements in plasma Aβ42, APP, BACE1, APPmRNA, BACE1mRNA (p<0.001) levels and information, arithmetic, digit span, vocabulary, block design and picture arrange scores (p<0.05) in the intervention group over the control group. According to mixed-model analysis, vitamin D group had significant increase in full scale IQ during follow-up period (p<0.001).ConclusionsDaily oral vitamin D supplementation (800 IU/day) for 12 months may improve cognitive function and decrease Aβ-related biomarkers in elderly patients with AD. Larger scale longer term randomised trials of vitamin D are needed.Trial registration numberChiCTR-IIR-16009549.
First Passage Time Distribution for Spiking Neuron with Delayed Excitatory Feedback
Authors: Shchur Olha , Vidybida Alexander 
Published: July 2019

A class of spiking neuronal models with threshold 2 is considered. It is defined by a set of conditions typical for basic threshold-type models, such as the leaky integrate-and-fire (LIF) or the binding neuron model, and also for some artificial neurons. A neuron is stimulated with a Poisson stream of excitatory impulses. Each output impulse is conveyed through the feedback line to the neuron input after finite delay [Formula: see text]. This impulse is identical to those delivered from the input stream. We have obtained a general relation allowing calculating exactly the probability density function (PDF) [Formula: see text] for distribution of the first passage time of crossing the threshold, which is the distribution of output interspike intervals (ISI) values for this neuron. The calculation is based on known PDF [Formula: see text] for that same neuron without feedback, intensity of the input stream [Formula: see text] and properties of the feedback line. Also, we derive exact relation for calculating the moments of [Formula: see text] based on known moments of [Formula: see text].The obtained general expression for [Formula: see text] is checked numerically using Monte Carlo simulation for the case of LIF model. The course of [Formula: see text] has a [Formula: see text]-function-type peculiarity. This fact contributes to the discussion about the possibility to model neuronal activity with Poisson process, supporting the “no” answer.
Chronic exercise training prevents coronary artery stiffening in aortic-banded miniswine: role of perivascular adipose-derived advanced glycation end products
Authors: Ouyang An , Olver T. Dylan , Emter Craig A. , Fleenor Bradley S. 
Published: July 2019

Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness, yet the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. We hypothesized that both chronic continuous and interval exercise training would prevent coronary PVAT-mediated AGE secretion and arterial stiffness. Yucatan miniature swine were divided into four groups: control-sedentary (CON), aortic banded sedentary-heart failure (HF), aortic banded HF-continuous exercise trained (HF+CONT), and aortic banded HF-interval exercise trained (HF+IT). The left circumflex and right coronary arteries underwent ex vivo mechanical testing, and arterial AGE, elastin, and collagen were assessed. Coronary elastin elastic modulus (EEM) and elastin protein were lower and AGE was increased with HF compared with CON, which was prevented by both HF+CONT and HF+IT. Mouse aortic segments treated with swine coronary PVAT conditioned medium had lower EEM and elastin content and greater AGE secretion and arterial AGE accumulation in HF compared with CON, which was prevented by both HF+CONT and HF+IT. Aminoguanidine (AMG), an AGE inhibitor, prevented the reduction in EEM, arterial elastin content, and AGE accumulation in mouse aortic segments treated with PVAT conditioned medium in the HF group. Our data demonstrate efficacy for chronic continuous and interval exercise to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a preclinical miniswine model of pressure overload-induced HF. NEW & NOTEWORTHY Our findings show that chronic continuous and interval exercise training regimens prevent coronary artery stiffness associated with inhibition of perivascular adipose tissue-derived advanced glycation end products in a translational pressure overload-induced heart failure model potentially providing an effective therapeutic option for heart failure patients.
Interleukin-1 receptor accessory proteins are required for normal homeostatic responses to sleep deprivation
Authors: Nguyen Joseph , Gibbons Cody M. , Dykstra-Aiello Cheryl , Ellingsen Riley , Koh Khia Min Sabrina , Taishi Ping , Krueger James M. 
Published: July 2019

Interleukin-1β (IL1) is a sleep regulatory substance. The IL1/IL1 type 1 receptor complex requires a receptor accessory protein (AcP) to signal. There are three isoforms of AcP. In the current experiments, mice lacking a neuron-specific isoform, called AcPb knockout (AcPb KO), or mice lacking AcP + AcPb isoforms (AcP KO) or wild-type (WT) mice were used. Spontaneous sleep and sleep responses to sleep deprivation (SD) between zeitgeber time (ZT) 20–ZT4 and ZT8–ZT16 were characterized. Furthermore, somatosensory cortical protein extracts were examined for phosphorylated (p) proto-oncogene tyrosine-protein kinase sarcoma (Src) and p38MAPK levels at ZT4 and ZT16 and after SD. Spontaneous sleep was similar in the three strains, except rapid eye movement sleep (REMS) duration between ZT12–ZT16 was greater in AcP KO than WT mice. After SD at ZT4, only WT mice had non-REMS (NREMS) rebounds. All mouse strains lacked an NREMS rebound after SD at ZT16. All strains after both SD periods had REMS rebounds. AcPb KO mice, but not AcP KO mice, had greater EEG delta wave (0.5–4 Hz) power during NREMS than WT mice. p-Src was very low at ZT16 but high at ZT4, whereas p-p38MAPK was low at ZT4 and high at ZT16. p-p38MAPK levels were not sensitive to SD. In contrast, p-Src levels were less after SD at the P = 0.08 level of significance in the strains lacking AcPb. We conclude that AcPb is required for NREMS responses to sleep loss, but not for SD-induced EEG delta wave or REMS responses. NEW & NOTEWORTHY Interleukin-1β (IL1), a well-characterized sleep regulatory substance, requires an IL1 receptor accessory protein (AcP); one of its isoforms is neuron-specific (called AcPb). We showed that in mice, AcPb is required for nonrapid eye movement sleep responses following 8 h of sleep loss ending 4 h after daybreak but did not affect rapid eye movement sleep rebound. Sleep loss reduced phosphorylation of proto-oncogene tyrosine-protein kinase sarcoma but not of the less sensitive p38MAPK, downstream IL1 signaling molecules.
ЯКІСТЬ ПИТНОЇ ВОДИ ЯК ОДНА З ДЕТЕРМІНАНТ ГРОМАДСЬКОГО ЗДОРОВ’Я В ЗАХІДНОМУ РЕГІОНІ УКРАЇНИ
Authors: Lototska I. V. , Kondratjuk V. A. , Kucher S. V. 
Published: July 2019

Відомо, що здоров'я людини значною мірою залежить від якості води, яку вона споживає.
Мета: провести аналіз деяких показників захворюваності населення західних областей України, які розташовані в басейні р. Дністер.
Матеріали і методи. При проведенні дослідження використано дані Державного комітету статистики України за 2015 р., застосовано статистичний метод.
Результати. У результаті проведеного аналізу було встановлено, що загальна захворюваність найбільша в Івано-Франківській області. Захворюваність на інфекційні та паразитарні хвороби переважає в Чернівецькій області. Кількість новоутворень найбільше реєструють в Львівській області. Найпоширенішими для населення західних областей є хвороби крові, кровотворних органів та окремі порушення із залученням імунного механізму. Щодо уперше зареєстрованих випадків хвороб органів травлення, то вони є характерними для Івано-Франківської, Хмельницької та Львівської областей.
Висновки. У Західному регіоні України на першому місці за кількістю уперше зареєстрованих випадків за­хво­рювань населення за класами хвороб є Івано-Франківська область, у якій чотири з п’яти класів захворювань значно перевищують середні по Україні показники. Причиною цього може бути низька якість питної води. Адже це єдина область в Західному регіоні України, в якій більшість населення споживає воду з поверхневих джерел, на якість якої можуть впливати промислові підприємства хімічної, енергетичної, нафтогазовидобувної, деревообробної та інших галузей.
FERNANDO PESSOA LEITOR DE PASCAL E O PROJETO DO LIVRO DO DESASSOSSEGO
Authors: Ribeiro Nuno , Souza Cláudia 
Published: July 2019

O presente artigo visa explorar as relações entre Pascal e Pessoa tendo por base o impacto da obra do autor francês tanto na estruturação quanto nas temáticas presentes ao longo do projeto do Livro do Desassossego. Com efeito, na Biblioteca Particular de Pessoa encontramos livros de e sobre Pascal que se encontram sublinhados e anotados pelo autor português e nos possibilitam certificar o interesse de Pessoa pelo pensamento pascaliano. Para além disso, o espólio de Pessoa oferece-nos um conjunto de fragmentos que nos permitem elucidar até que ponto a leitura da obra de Pascal viria a ser importante para a elaboração dos fragmentos do Livro do Desassossego. Assim, tendo por base a análise da presença do nome e do pensamento de Pascal em fragmentos do espólio de Pessoa, o presente artigo explicita qual o papel da leitura pessoana de Pascal na elaboração do projeto do Livro do Desassossego
Wie Samaria so auch Jerusalem
Authors: Weingart Kristin 
Published: July 2019

AbstractBy naming Micah and citing Mi 3:12 the book of Jeremiah (Jer 26:18) provides an explicit example of the reception of older prophetic texts and traditions in later compositions. In addition, Jer 26:18f. also offer a historical setting for Micah’s activity—the time of Hezekiah and most probably the events of 701 BCE. The paper argues that the literary history of the book of Micah substantiates the assumption of an early Micah composition originating from the late 8th century BCE and discusses the extent, structure, and pragmatics of the composition which comprises Mi *1:5-3:12. Focussing on the situation of the eminent Assyrian threat, Micah uses the the fate of Samaria as a rhetorical device in order to persuade his Judean addressees of his message. In doing so, Micah not only displays a familiarity with North Israelite prophetic traditions, the composition also adopts compositional elements and rhetorical strategies found in Hosea and Amos.
The Effect of Ageing on Optimal Integration of Conflicting and Non-Conflicting Visual–Haptic Stimuli
Authors: Couth Samuel , Poole Daniel , Gowen Emma , Champion Rebecca A. , Warren Paul A. , Poliakoff Ellen 
Published: July 2019

Abstract
Multisensory integration typically follows the predictions of a statistically optimal model whereby the contribution of each sensory modality is weighted according to its reliability. Previous research has shown that multisensory integration is affected by ageing, however it is less certain whether older adults follow this statistically optimal model. Additionally, previous studies often present multisensory cues which are conflicting in size, shape or location, yet naturally occurring multisensory cues are usually non-conflicting. Therefore, the mechanisms of integration in older adults might differ depending on whether the multisensory cues are consistent or conflicting. In the current experiment, young () and older () adults were asked to make judgements regarding the height of wooden blocks using visual, haptic or combined visual–haptic information. Dual modality visual–haptic blocks could be presented as equal or conflicting in size. Young and older adults’ size discrimination thresholds (i.e., precision) were not significantly different for visual, haptic or visual–haptic cues. In addition, both young and older adults’ discrimination thresholds and points of subjective equality did not follow model predictions of optimal integration, for both conflicting and non-conflicting cues. Instead, there was considerable between subject variability as to how visual and haptic cues were processed when presented simultaneously. This finding has implications for the development of multisensory therapeutic aids and interventions to assist older adults with everyday activities, where these should be tailored to the needs of each individual.
Effect of Tropical Nonconvective Condensation on Uncertainty in Modeled Projections of Rainfall
Authors: Stephens Benjamin A. , Jackson Charles S. , Wagman Benjamin M. 
Published: July 2019

Abstract
We find that part of the uncertainty in the amplitude and pattern of the modeled precipitation response to CO2 forcing traces to tropical condensation not directly involved with parameterized convection. The fraction of tropical rainfall associated with large-scale condensation can vary from a few percent to well over half depending on model details and parameter settings. In turn, because of the coupling between condensation and tropical circulation, the different ways model assumptions affect the large-scale rainfall fraction also affect the patterns of the response within individual models. In two single-model ensembles based on the National Center for Atmospheric Research (NCAR) Community Atmosphere Model (CAM), versions 3.1 and 5.3, we find strong correlations between the fraction of tropical large-scale rain and both climatological rainfall and circulation and the response to CO2 forcing. While the effects of an increasing tropical large-scale rain fraction are opposite in some ways in the two ensembles—for example, the Hadley circulation weakens with the large-scale rainfall fraction in the CAM3.1 ensemble while strengthening in the CAM5.3 ensemble—we can nonetheless understand these different effects in terms of the relationship between latent heating and circulation, and we propose explanations for each ensemble. We compare these results with data from phase 5 of the Coupled Model Intercomparison Project (CMIP5), for which some of the same patterns hold. Given the importance of this partitioning, there is a need for constraining this source of uncertainty using observations. However, since a “large-scale rainfall fraction” is a modeling construct, it is not clear how observations may be used to test various modeling assumptions determining this fraction.
Clarifying the Baroclinic Contribution to the Great Plains Low-Level Jet Frequency Maximum
Authors: Gebauer Joshua G. , Shapiro Alan 
Published: July 2019

Abstract
The frequency and intensity of the Great Plains nocturnal low-level jet (LLJ) are enhanced by baroclinicity over the sloped terrain of the region. A classical description of baroclinic-induced diurnal wind oscillations over the Great Plains considers differential heating of the slope with respect to air at the same elevation far removed from the slope, but with buoyancy constant along the slope (Holton mechanism). Baroclinicity can also occur due to differential heating of the slope itself, which creates a gradient in buoyancy along the slope. The relative prevalence of the two types of baroclinicity in this region has received scant attention in the literature. The present study uses 19 years of data from the Oklahoma Mesonet to evaluate the characteristics of along-slope buoyancy gradients over the region. A mean negative afternoon along-slope buoyancy gradient (east–west gradient) is found over Oklahoma. The sign of this afternoon buoyancy gradient is favorable for LLJ formation, as it results in the strongest southerly geostrophic wind near the ground around sunset, which is conducive to nocturnal jet formation via the inertial oscillation mechanism. The negative afternoon buoyancy gradient is at least partially created by an east–west gradient in diurnal heating and is stronger and more consistent in the summer months, which is when LLJs are most frequent. The contribution of the along-slope buoyancy gradient to the low-level geostrophic wind was found to be as important as the contribution of the Holton mechanism. Overall, these results indicate that along-slope buoyancy gradients should be accounted for in studies of LLJ dynamics over the Great Plains.
Validation of Snow Multibands in the Comma Head of an Extratropical Cyclone Using a 40-Member Ensemble
Authors: Connelly Ryan , Colle Brian A. 
Published: July 2019

Abstract
This paper investigates the ability of the Weather Research and Forecasting (WRF) Model in simulating multiple small-scale precipitation bands (multibands) within the extratropical cyclone comma head using four winter storm cases from 2014 to 2017. Using the model output, some physical processes are explored to investigate band prediction. A 40-member WRF ensemble was constructed down to 2-km grid spacing over the Northeast United States using different physics, stochastic physics perturbations, different initial/boundary conditions from the first five perturbed members of the Global Forecast System (GFS) Ensemble Reforecast (GEFSR), and a stochastic kinetic energy backscatter scheme (SKEBS). It was found that 2-km grid spacing is adequate to resolve most snowbands. A feature-based verification is applied to hourly WRF reflectivity fields from each ensemble member and the WSR-88D radar reflectivity at 2-km height above sea level. The Method for Object-Based Diagnostic Evaluation (MODE) tool is used for identifying multibands, which are defined as two or more bands that are 5–20 km in width and that also exhibit a &gt;2:1 aspect ratio. The WRF underpredicts the number of multibands and has a slight eastward position bias. There is no significant difference in frontogenetical forcing, vertical stability, moisture, and vertical shear between the banded versus nonbanded members. Underpredicted band members tend to have slightly stronger frontogenesis than observed, which may be consolidating the bands, but overall there is no clear linkage in ambient condition errors and band errors, thus leaving the source for the band underprediction motivation for future work.