bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved glycaemic control and lower hypoglycaemia risk with reduced prior oral antidiabetes drug therapy in patients with type 2 diabetes treated with insulin glargine 300 U/mL
Authors: Dailey George , Reid Timothy , White John , Chao Jason , Zhou Fang L. , Paranjape Sachin , Berhanu Paulos 
Published: September 2018

SummaryAimsData from the EDITION 3 randomized study and the Clinformatics claims database were analysed to determine whether insulin glargine 300 U/mL (Gla‐300) could provide insulin‐naive patients with type 2 diabetes (T2D) on oral antidiabetes drugs (OADs) with reductions in prior OAD therapy without compromising glycaemic control, and while preserving its known low incidence of hypoglycaemia compared with insulin glargine 100 U/mL (Gla‐100).MethodsPatient‐level data from EDITION 3 and de‐identified data from the Clinformatics real‐world claims database were analysed.ResultsAt baseline, 70% of patients in EDITION 3 were on a background of ≥2 OADs. Among the 435 and 437 patients who initiated basal insulin with Gla‐300 and Gla‐100, respectively, at Month 6, 336 (77%) and 338 (77%) were using ≤1 OAD. Adding Gla‐300 or Gla‐100 similarly allowed for a reduction in background OAD medication in the Clinformatics dataset (N = 6430), such that, at 6 months postbasal insulin initiation, 14% of patients were no longer taking any OADs. In the analysis of the EDITION 3 study, reduction in OAD burden did not compromise glycaemic benefit, and the low incidence of hypoglycaemia associated with Gla‐300 compared with Gla‐100 was also preserved. Documented symptomatic hypoglycaemia (blood glucose ≤70 mg/dL) occurred in 30.5% vs 41.0% of patients treated with Gla‐300 and Gla‐100, respectively (P = 0.0442).ConclusionPatients with T2D who initiate basal insulin with Gla‐300 could potentially reduce their prior OAD use without compromising glycaemic control and with less hypoglycaemia than with Gla‐100.
The tyrosine kinase inhibitor dasatinib reduces the growth of intracellular Mycobacterium tuberculosis despite impairing T‐cell function
Authors: Wehrstedt Stephanie , Kubis Jan , Zimmermann Andreas , Bruns Heiko , Mayer Daniel , Grieshober Mark , Stenger Steffen 
Published: September 2018

AbstractTyrosine kinases are checkpoints for multiple cellular pathways and dysregulation induces malignancies, most notably chronic myeloid leukemia (CML). Inhibition of Abl‐tyrosine kinases has evolved as a new concept for the treatment of CML and other malignant diseases. Due to the multiple immune‐modulatory pathways controlled by tyrosine kinases, treatment with tyrosine kinase inhibitors (TKIs) will not only affect the biology of malignant cells but also modulate physiological immune functions. To understand the effects of TKIs on host defense against intracellular bacteria, we investigated the immunological impact of the dual Abl/Src TKI dasatinib on the cellular immune response to Mycobacterium tuberculosis (Mtb). Our results demonstrate that dasatinib impaired proliferation, cytokine release (IFN‐γ, TNF‐α, GM‐CSF), expression of granulysin and degranulation of cytotoxic effector molecules of human Mtb‐specific T‐lymphocytes by inhibition of lymphocyte‐specific protein tyrosine kinase (Lck) phosphorylation. Despite this profound inhibition of T‐cell function, dasatinib suppressed growth of virulent Mtb in human macrophages co‐cultured with autologous Mtb‐specific T‐cells (49±15%). Functional analysis suggested that growth inhibition is due to dasatinib‐triggered lysosomal acidification in Mtb‐infected macrophages. These results highlight the significance of innate immune responses, i.e. acidification of lysosomes, which control the multiplication of intracellular bacteria despite the lack of efficient T‐cell support.
New advances in microfluidic flow cytometry
Authors: Gong Yanli , Fan Na , Yang Xu , Peng Bei , Jiang Hai 
Published: September 2018

AbstractIn recent years, researchers are paying the increasing attention to the development of portable microfluidic diagnostic devices including microfluidic flow cytometry for the point‐of‐care testing. Microfluidic flow cytometry, where microfluidics and flow cytometry work together to realize novel functionalities on the microchip, provides a powerful tool for measuring the multiple characteristics of biological samples. The development of a portable, low‐cost, and compact flow cytometer can benefit the health care in underserved areas such as Africa or Asia. In this article, we review recent advancements of microfluidics including sample pumping, focusing and sorting, novel detection approaches, and data analysis in the field of flow cytometry. The challenge of microfluidic flow cytometry is also examined briefly.
Clonal architecture in patients with myelodysplastic syndromes and double or minor complex abnormalities: Detailed analysis of clonal composition, involved abnormalities, and prognostic significance
Authors: Schanz Julie , Solé Francesc , Mallo Mar , Luño Elisa , Cervera Jose , Granada Isabel , Hildebrandt Barbara , Slovak Marylin L. , Ohyashiki Kazuma , Fonatsch Christa , Pfeilstöcker Michael , Nösslinger Thomas , Valent Peter , Giagounidis Aristoteles , Aul Carlo , Lübbert Michael , Stauder Reinhard , Krieger Otto , Le Beau Michelle M. , Bennett John M. , Greenberg Peter , Germing Ulrich , Haase Detlef 
Published: September 2018

AbstractThe study analyzes the clonal architecture and the abnormalities involved in a series of 191 patients with myelodysplastic syndromes (MDS) and 2‐3 clonal abnormalities. All patients were extracted from an international database. The patients were classified into six clonal subtypes (2A‐3C) based on the number of abnormalities and the presentation of unrelated clones (UC) and/or a clonal evolution. UC were detected in 23/191 patients (12%). The composition of UC showed great variability. The only recurrent combination of abnormalities was del(5q) and + 8 in 8 of 23 patients (35%). In patients with clonal evolution, the clone size of the primary and secondary clone varied: Patients with −7 and + 8 in the primary clone showed a larger primary and a smaller secondary clone (−7: median 74% vs 10%; +8 73% vs 18%) while patients with del(5q) in the primary clone showed a smaller primary and a larger secondary clone (33% vs 61%). Univariate and multivariate analyses showed no significant differences regarding overall or AML‐free survival between the clonal subtypes. Only the subtype 3C (3 abnormalities and clonal evolution) was an independent risk factor for developing AML (Hazard Ratio 5.5 as compared to subtype 2A, P < .05). Finally, our study confirms that the number of abnormalities clearly defines a significant risk factor for overall‐ as well as AML‐free survival. Importantly, in patients with more than one clone, the calculation of the number of abnormalities in the entire sample instead of the number of abnormalities per clone allows a higher prognostic accuracy.
Diagenetic characteristics and reservoir quality in tight gas sandstones: A case study of the Shanxi Formation in the north‐eastern Ordos Basin, China
Authors: Shao Xinhe , Pang Xiongqi , Jiang Fujie , Li Longlong , Huyan Yuying , Zheng Dingye 
Published: September 2018

Reservoir quality is critical in tight gas exploration. A systematic study of the petrological, petrophysical, and diagenetic characteristics of the Shanxi Formation sandstones in the north‐eastern Ordos Basin (China) was undertaken to characterize the pore system of these tight sandstones and recognize the distribution of reservoirs favourable for hydrocarbon accumulation. The results suggest that the Shanxi Formation sandstone has low compositional and moderate textural maturity, with its porosity ranging from 0.7% to 11.8% (average 5.97%) and permeability ranging from 0.001 to 2.77 mD (average 0.36 mD). In addition, thin section and SEM observations suggest that the sandstone is dominated by secondary dissolution pores, primary intergranular pores as well as microfractures, and has undergone compaction, cementation, and dissolution. Diagenetic minerals, such as carbonate cements, authigenic quartz, clay minerals, and dissolved feldspar, are identified. Fluid inclusions are observed in healed microfractures of quartz grains and in quartz overgrowths, while the homogenization temperatures of fluid inclusions in healed microfractures and in quartz overgrowth are in the ranges of 92.8–179.1°C (average 134.8°C) and 104.7–169.1°C (average 145.7°C), respectively. Authigenic kaolinite is sourced from the process of K‐feldspar dissolution, authigenic illite is sourced from transformation of smectite and kaolinite, while sources for quartz cements include mineral alteration and pressure dissolution. Selective dissolution of K‐feldspar in the presence of carbonate minerals is observed in the Shanxi Formation tight sandstones due to the different equilibrium constants of carbonate minerals and K‐feldspar leaching, resulting in dissolution pores associated with K‐feldspar. Reservoir quality in the Shanxi Formation tight sandstones is greatly influenced by diagenesis, as compaction and cementation are responsible for the loss of porosity while dissolution accounts for the enhancement of secondary porosity.
Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input‐deprived axonal activities in sensory deprived mouse models
Authors: Osanai Yasuyuki , Shimizu Takeshi , Mori Takuma , Hatanaka Nobuhiko , Kimori Yoshitaka , Kobayashi Kenta , Koyama Shinsuke , Yoshimura Yumiko , Nambu Atsushi , Ikenaka Kazuhiro 
Published: September 2018

AbstractOligodendrocytes myelinate neuronal axons to increase conduction velocity in the vertebrate central nervous system (CNS). Recent studies revealed that myelin formed on highly active axons is more stable compared to activity‐silenced axons, and length of the myelin sheath is longer in active axons as well in the zebrafish larva. However, it is unclear whether oligodendrocytes preferentially myelinate active axons compared to sensory input‐deprived axons in the adult mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer myelin sheaths on active axons and shorter sheaths on input‐deprived axons after long‐term sensory deprivation. To address these questions, we applied simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models of long‐term monocular eyelid suturing and unilateral whisker removal. We found that individual oligodendrocytes evenly myelinated normal and input‐deprived axons in the adult mouse CNS, and myelin sheath length on normal axons and input‐deprived axons formed by a single oligodendrocyte were comparable. Importantly, the average length of the myelin sheath formed by individual oligodendrocytes did change depending on relative abundance of normal against sensory‐input deprived axons, indicating an abundance of deprived axons near an oligodendrocyte impacts on myelination program by a single oligodendrocyte.
Education, and the balance between dynamic and stationary functional connectivity jointly support executive functions in relapsing–remitting multiple sclerosis
Authors: Lin Sue‐Jin , Vavasour Irene , Kosaka Brenda , Li David K. B. , Traboulsee Anthony , MacKay Alex , McKeown Martin J. 
Published: September 2018

AbstractGraphical network characteristics and nonstationary functional connectivity features, both derived from resting‐state functional magnetic resonance imaging (rsfMRI) data, have been associated with cognitive performance in healthy subjects. How these features jointly relate to cognition in diseased states has not been investigated. In this study, 46 relapsing–remitting multiple sclerosis subjects underwent rsfMRI scans and a focused cognitive battery. With a sliding window approach, we examined six dynamic network features that indicated how connectivity changed over time as well as six measures derived from graph theory to reflect static network characteristics. Multiset canonical correlation analysis (MCCA) was then carried out to investigate the relations between dynamic network features, stationary network characteristics, cognitive testing, demographic, disease severity, and mood. Multiple sclerosis (MS) subjects demonstrated weaker connectivity strength, decreased network density, reduced global changes, but increased changes in interhemispheric connectivity compared to controls. The MCCA model determined that executive functions and processing speed ability measured by Wechsler Adult Intelligence Scale IV (WAIS‐IV) Working Memory Index, WAIS‐IV Processing Speed Index, and the Verbal Fluency Test were positively correlated with education, dynamic connectivity, and static connectivity strength; while poor task switching was correlated with disease severity, psychiatric comorbidities such as depression, anxiety, and fatigue, and static network density. Taken together, our results suggest that better executive functioning in MS requires maintenance of a continued coordination between stationary and dynamic functional connectivity as well as the support of education, and dynamic functional connectivity may provide an additional cognitive biomarker of disease severity in the MS population.
Neural substrates of word category information as the basis of syntactic processing
Authors: Chen Luyao , Wu Junjie , Fu Yongben , Kang Huntae , Feng Liping 
Published: September 2018

AbstractThe ability to use word category information (WCI) for syntactic structure building has been hypothesized to be the essence of human language faculty. The neural substrate of the ability of using the WCI for the complex syntactic hierarchical structure processing, however, is yet unknown. Therefore, we directly conducted an fMRI experiment by using a pseudo‐Chinese artificial language with syntactic structures containing a center‐embedded relative clause. Thirty non‐Chinese native (Korean) speakers were randomly divided into two groups: one acquired WCI and WCI‐based syntactic rules (the WCI group) before the scanning session, and the other did not (the non‐WCI group). Both groups were required to judge the grammaticality of the testing sentences, with critical long‐distance dependencies between two elements (the main verb and the relativizer). Behaviorally, the WCI group's accuracy was significantly higher and its reaction time was shorter. The scanning results showed that the left superior temporal gyrus (STG) and Broca's area were more strongly activated for the WCI group, and the dynamic causal modeling analyses revealed a distinct effective connectivity pattern for this group. Therefore, the present research, for the first time, reveals that the activation of and the functional connectivity between Broca's area and the left STG play a critical role in the ability of the rule‐based use of the WCI which is crucial for complex hierarchical structure building, and might be substantially corresponding to the “labeling competence” within the linguistic framework.
The role of diversity in data‐driven analysis of multi‐subject fMRI data: Comparison of approaches based on independence and sparsity using global performance metrics
Authors: Long Qunfang , Bhinge Suchita , Levin‐Schwartz Yuri , Boukouvalas Zois , Calhoun Vince D. , Adalı Tülay 
Published: September 2018

AbstractData‐driven methods have been widely used in functional magnetic resonance imaging (fMRI) data analysis. They extract latent factors, generally, through the use of a simple generative model. Independent component analysis (ICA) and dictionary learning (DL) are two popular data‐driven methods that are based on two different forms of diversity—statistical properties of the data—statistical independence for ICA and sparsity for DL. Despite their popularity, the comparative advantage of emphasizing one property over another in the decomposition of fMRI data is not well understood. Such a comparison is made harder due to the differences in the modeling assumptions between ICA and DL, as well as within different ICA algorithms where each algorithm exploits a different form of diversity. In this paper, we propose the use of objective global measures, such as time course frequency power ratio, network connection summary, and graph theoretical metrics, to gain insight into the role that different types of diversity have on the analysis of fMRI data. Four ICA algorithms that account for different types of diversity and one DL algorithm are studied. We apply these algorithms to real fMRI data collected from patients with schizophrenia and healthy controls. Our results suggest that no one particular method has the best performance using all metrics, implying that the optimal method will change depending on the goal of the analysis. However, we note that in none of the scenarios we test the highly popular Infomax provides the best performance, demonstrating the cost of exploiting limited form of diversity.
The neurophysiological basis of developmental changes during sequential cognitive flexibility between adolescents and adults
Authors: Giller Franziska , Zhang Rui , Roessner Veit , Beste Christian 
Published: September 2018

AbstractCognitive flexibility is a major facet of executive functions and often refers to sequential task control; that is, it is very likely that one may re‐encounter a task that has previously been abandoned to carry out a different task. In the context of sequential cognitive flexibility, the “backward inhibition (BI) effect” has been studied quite extensively. Here we ask whether there are age‐related differences between adolescents and adults to overcome BI and what system‐neurophysiological mechanisms underlie these modulations. This was examined using a system neurophysiological study procedure combining event‐related potentials data with source localization and EEG signal decomposition methods. We show that sequential cognitive flexibility, and the ability overcome backward inhibition, is inferior in adolescents compared with adults. Accounting for intra‐individual variability in the neurophysiological data, this data suggest that two partly inter‐related processes underlie the differences between adolescents than adults to overcome backward inhibition: One process refers to the suppression of the inhibitory effect of the n‐1 trial on the n‐2 trial during perceptual categorization of incoming information that is associated with right inferior frontal regions. The other process refers to immature response selection and conflict monitoring mechanisms associated with regions in the medial frontal cortex.
How much does birth weight matter for child health in developing countries? Estimates from siblings and twins
Authors: McGovern Mark E. 
Published: September 2018

AbstractAbout 200 million children globally are not meeting their growth potential, and as a result will suffer the consequences in terms of future outcomes. I examine the effects of birth weight on child health and growth using information from 66 countries. I account for missing data and measurement error using instrumental variables and adopt an identification strategy based on siblings and twins. I find a consistent effect of birth weight on mortality risk, stunting, wasting, and coughing, with some evidence for fever, diarrhoea, and anaemia. Bounds analysis indicates that coefficients may be substantially underestimated due to mortality selection. Improving the pre‐natal environment is likely to be important for helping children reach their full potential.
The effect of weight on labor market outcomes: An application of genetic instrumental variables
Authors: Böckerman Petri , Cawley John , Viinikainen Jutta , Lehtimäki Terho , Rovio Suvi , Seppälä Ilkka , Pehkonen Jaakko , Raitakari Olli 
Published: September 2018

AbstractThis paper contributes to the literature on the labor market consequences of obesity by using a novel instrument: genetic risk score, which reflects the predisposition to higher body mass index (BMI) across many genetic loci. We estimate instrumental variable models of the effect of BMI on labor market outcomes using Finnish data that have many strengths, for example, BMI that is measured rather than self‐reported, and data on earnings and social income transfers that are from administrative tax records and are thus free of the problems associated with nonresponse, reporting error or top coding. The empirical results are sensitive to whether we use a narrower or broader genetic risk score, and to model specification. For example, models using the narrower genetic risk score as an instrument imply that a one‐unit increase in BMI is associated with 6.9% lower wages, 1.8% fewer years employed, and a 3 percentage point higher probability of receiving any social income transfers. However, when we use a newer, broader genetic risk score, we cannot reject the null hypothesis of no effect. Future research using genetic risk scores should examine the sensitivity of their results to the risk score used.
Tillage‐induced surface roughness and topographic conditions for rill initiation in Angereb watershed, Ethiopia
Authors: Gessesse Gizaw Desta 
Published: September 2018

AbstractRill erosion makes up one source of sediment detachment and transport on agricultural fields in the Ethiopia highlands. It is so important to understand the conditions for rill initiation and demarcating rill prone areas for management planning. In this paper, we estimated rill incision considering tillage‐induced surface roughness, upslope contributing area, and slope gradient. Field experiments were installed on two fresh‐tilled smallholder agricultural plots of 3.2 m wide and 14.4 m long in the Angereb watershed of the upper Lake Tana subbasin in Ethiopia. The plots mainly represent clay and sandy clay loam soils. Time series digital elevation models generated by digital photogrammetry were used to derive topographic and surface roughness variables corresponding to 46, 116, 174, and 410‐mm cumulative rainfall. A non‐linear regression model was fitted on the slope gradient, upslope contributing area, and surface random roughness of individual rills to predict threshold area for rill initiation. Subsequent rainfall events have resulted in rough surfaces later. The change in random roughness in each rainfall event compared with the first stage amounts to 1.81, 1.62, 1.68, and 1.74 cm on clay soil and −0.05, 0.86, 1.55, and 2.06 cm on sandy clay loam soil. Prediction of the threshold area for rill initiation has improved when considering random roughness and its temporal changes. The average prediction parameter of the unit contributing area was 0.03 ± 0.05 and 0.04 ± 0.04, and of the random roughness was −0.08 ± 0.13 and −0.13 ± 0.05 on clay and sandy clay loam soils, respectively. The prediction resulted in a threshold area between 0.20 and 0.47 (average of 0.36 ± 0.11) on clay soil and 0.28 and 0.39 (average of 0.34 ± 0.05) on sandy clay loam soil. The significant variation of threshold area (p < 0.05) over the subsequent rainfall events ensures the role of incorporating surface roughness in predicting rill initiation. The result demonstrates the need to consider the variable threshold area over rainfall periods for rill incision modelling and indirectly improves the slope–length factor of erosion models.