bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel targets to cure primary myelofibrosis from studies on Gata1low mice
Authors: Zingariello Maria , Martelli Fabrizio , Verachi Paola , Bardelli Claudio , Gobbo Francesca , Mazzarini Maria , Migliaccio Anna Rita 
Published: November 2019

AbstractIn 2002, we discovered that mice carrying the hypomorphic Gata1low mutation that reduces expression of the transcription factor GATA1 in megakaryocytes (Gata1low mice) develop myelofibrosis, a phenotype that recapitulates the features of primary myelofibrosis (PMF), the most severe of the Philadelphia‐negative myeloproliferative neoplasms (MPNs). At that time, this discovery had a great impact on the field because mutations driving the development of PMF had yet to be discovered. Later studies identified that PMF, as the others MPNs, is associated with mutations activating the thrombopoietin/JAK2 axis raising great hope that JAK inhibitors may be effective to treat the disease. Unfortunately, ruxolitinib, the JAK1/2 inhibitor approved by FDA and EMEA for PMF, ameliorates symptoms but does not improve the natural course of the disease, and the cure of PMF is still an unmet clinical need. Although GATA1 is not mutated in PMF, reduced GATA1 content in megakaryocytes as a consequence of ribosomal deficiency is a hallmark of myelofibrosis (both in humans and mouse models) and, in fact, a driving event in the disease. Conversely, mice carrying the hypomorphic Gata1low mutation express an activated TPO/JAK2 pathway and partially respond to JAK inhibitors in a fashion similar to PMF patients (reduction of spleen size but limited improvement of the natural history of the disease). These observations cross‐validated Gata1low mice as a bona fide animal model for PMF and prompted the use of this model to identify abnormalities that might be targeted to cure the disease. We will summarize here data generated in Gata1low mice indicating that the TGF‐β/P‐selectin axis is abnormal in PMF and represents a novel target for its treatment.
Physiologically Based Pharmacokinetic Approach Can Successfully Predict Pharmacokinetics of Citalopram in Different Patient Populations
Authors: Wu Xuemei , Zhang Hongfei , Miah Mohammad Kowser , Caritis Steve N. , Venkataramanan Raman 
Published: November 2019

AbstractA physiologically based pharmacokinetic model (PBPK) was built for citalopram using Simcyp‐based absorption, distribution, metabolism, and excretion simulator. Various physicochemical properties of citalopram were obtained from the published literature. The in vitro‐in vivo extrapolation method was used to predict clearance in humans from recombinant enzyme data. Tissue distribution was predicted using parameter estimation function to fit the developed model to the observed concentration‐versus‐time data using nonlinear mixed‐effects modeling approach. The model was verified by comparing the PBPK‐based predictions with the observed pharmacokinetic (PK) profiles of citalopram in 26 clinical studies across a dose range of 10 to 60 mg. The predicted PK parameters of citalopram after intravenous dosing were within the −10% to 22% of the corresponding PK parameters obtained from the studies with quantified data sets. Most of the predicted PK parameters of citalopram after single‐dose oral administration were within the 70%‐130% range of the corresponding PK parameters obtained from observed data from 8 studies. After multidose oral administration, percentage error of Cmax and AUC was between −21% and 25% and −31% and 21%, respectively. Most of the observed data were within the 5th and 95th percentile interval of the variability around the predicted plasma concentrations. With the established model, the PK profiles in geriatric populations, populations with cytochrome P450 (CYP) 2C19 and/or 2D6 extensive metabolizers or poor metabolizers were predicted, and the predictions were in good agreement with the observed data. The model developed is robust to represent the absorption and disposition of citalopram and can predict the impact of patient covariates, such as age and genetic polymorphism of CYP2C19 and CYP2D6, on exposure of citalopram.
Artificial intelligence in genetic services delivery: Utopia or apocalypse?
Authors: Kearney Elizabeth , Wojcik Antonina , Babu Deepti 
Published: November 2019

AbstractArtificial intelligence (AI) technologies have a long history, with increasing presence and potential in society and medicine. Much of the medical literature is highly optimistic about AI and machine learning, but fears also exist that healthcare professionals will be replaced by machines. AI remains mysterious for many practitioners, so this paper aims to unwind both hype and fear related to the technology for genetics professionals. After an historical introduction to AI in understandable and practical terms, we review its limitations. Building upon this foundation, we discuss current AI applications in medicine, including genomics and genetic counseling, offering grounded ideas about the impact and role of AI in genetic counseling and delivery of genetic services. Since AI is already being used in genomics today, now is the time to fundamentally understand what it is, how it is being used, what its limitations are, and how it will continue to be integrated into genetics as we look ahead.
TRAF family molecules in T cells: Multiple receptors and functions
Authors: Arkee Tina , Bishop Gail A. 
Published: November 2019

Abstract
The TNFR superfamily of receptors, the major focus of the recent TNFR Superfamily Conference held in June 2019, employ the TNFR-associated factor (TRAF) family of adaptor proteins in key aspects of their signaling pathways. Although many early studies investigated TRAF functions via exogenous overexpression in nonhematopoietic cell lines, it has subsequently become clear that whereas TRAFs share some overlap in function, each also plays unique biologic roles, that can be highly context dependent. This brief review summarizes the current state of knowledge of functions of each of the TRAF molecules that mediate important functions in T lymphocytes: TRAFs 1, 2, 3, 5, and 6. Due to our current appreciation of the contextual nature of TRAF function, our focus is upon findings made specifically in T lymphocytes. Key T cell functions for each TRAF are detailed, as well as future knowledge gaps of interest and importance.
Distinguishing human peripheral blood CD16+ myeloid cells based on phenotypic characteristics
Authors: Fromm Phillip D. , Silveira Pablo A. , Hsu Jennifer L. , Papadimitrious Michael S. , Lo Tsun-Ho , Ju Xinsheng , Kupresanin Fiona , Romano Adelina , Hsu Wei-Hsun , Bryant Christian E. , Kong Benjamin , Abadir Edward , Mekkawy Ahmed , M. McGuire Helen , Groth Barbara Fazekas de St. , Cunningham Ilona , Newman Elizabeth , Gibson John , Hogarth P. Mark , Hart Derek N. J. , Clark Georgina J. 
Published: November 2019

Abstract
Myeloid lineage cells present in human peripheral blood include dendritic cells (DC) and monocytes. The DC are identified phenotypically as HLA-DR+ cells that lack major cell surface lineage markers for T cells (CD3), B cells (CD19, CD20), NK cells (CD56), red blood cells (CD235a), hematopoietic stem cells (CD34), and Mo that express CD14. Both DC and Mo can be phenotypically divided into subsets. DC are divided into plasmacytoid DC, which are CD11c−, CD304+, CD85g+, and myeloid DC that are CD11c+. The CD11c+ DC are readily classified as CD1c+DC and CD141+ DC. Monocytes are broadly divided into the CD14+CD16− (classical) and CD14dimCD16+ subsets (nonclassical). A population of myeloid-derived cells that have DC characteristics, that is, HLA-DR+ and lacking lineage markers including CD14, but express CD16 are generally clustered with CD14dimCD16+ monocytes. We used high-dimensional clustering analyses of fluorescence and mass cytometry data, to delineate CD14+ monocytes, CD14dimCD16+ monocytes (CD16+Mo), and CD14− CD16+DC (CD16+DC). We sought to identify the functional and kinetic relationship of CD16+DC to CD16+Mo. We demonstrate that differentiation of CD16+DC and CD16+Mo during activation with IFNγ in vitro and as a result of an allo-hematopoietic cell transplant (HCT) in vivo resulted in distinct populations. Recovery of blood CD16+DC in both auto- and allo-(HCT) patients after myeloablative conditioning showed similar reconstitution and activation kinetics to CD16+Mo. Finally, we show that expression of the cell surface markers CD300c, CCR5, and CLEC5a can distinguish the cell populations phenotypically paving the way for functional differentiation as new reagents become available.
Electric field distribution study in inhomogeneous biological tissues
Authors: Sieni Elisabetta , Sgarbossa Paolo , Mognaschi Maria Evelina , Forzan Michele , Parupudi Tejasvi , Mittal Lakshya , Camarillo Ignacio G. , Sundararajan Raji 
Published: November 2019

AbstractMost solid tumors are inhomogeneous, because of the different types of cells present, different tissues and fat, etc, along with irregular vascularization, pH variation, and heterogeneous oxygen concentration. It is of interest to study the electric field distribution when electrochemotherapy is administered. The variations in the physical and hence the electrical properties, such as the resistance (or conductance), will vary, and parts of the tumor might not get the same electric field and hence will not have the required or the desired efficacy. In this study, the effect of tissue inhomogeneity is explored using potato and apple tissue samples. For this purpose, agar gel and other tissue mimic materials are used to create the inhomogeneity and pulsed to study the effect of electrical pulses. In addition, the electric field distribution is studied using a numerical model to evaluate the effect of tissue inhomogeneity in terms of electric field distribution when electroporation is applied to permeabilize cells, for enhanced drug uptake. The electric field is evaluated by means of finite element analysis and is compared with the distribution found in a phantom model. Good correlation is obtained between the experimental and simulation results. This research has the potential to study the real tumor inhomogeneity conditions.
Managing uncertain tasks in technology‐intensive project environments: A multi‐method study of task closure and capacity management decisions
Authors: Narayanan Sriram , Balasubramanian Sridhar , Swaminathan Jayashankar M. , Zhang Ying 
Published: November 2019

AbstractEngineers working on tasks in technology‐intensive project environments face substantial task resolution uncertainty. This can result in poor capacity utilization as they expend effort on tasks that are not successfully resolved. A deeper understanding of task‐related uncertainty can help the firm optimize effort allocation across tasks by implementing well‐designed task closure policies that facilitate superior capacity utilization and capacity planning. In this article, we characterize the empirical distribution of task uncertainty and demonstrate how the resolution process affects task outcomes in project environments. Using a combination of empirical estimation, and analytical and simulation modeling, we develop insights into task‐related decision‐making and engineer effort allocation. Using real‐world task resolution data from a software maintenance setting, we first model and estimate a beta‐geometric survival distribution which indicates that the likelihood of successful task resolution substantially reduces with the time a task remains in the system. Using analytical and simulation modeling, we then examine the implications of imposing task closure policies to improve engineer effort allocation and increase system productivity. We demonstrate that adopting well‐designed task closure policies can significantly improve engineer resource utilization in capacity‐constrained settings without a substantial negative impact on project outcomes. We discuss the implications of our research for theory and practice.
Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project
Authors: Goode Adam P. , Schwartz Todd A. , Kraus Virginia B. , Huebner Janet L. , George Steven Z. , Cleveland Rebecca J. , Gracely Richard , Jimenez Maria , DeFrate Louis E. , Chen Jun , Golightly Yvonne M. , Jordan Joanne M. 
Published: November 2019

ABSTRACTThe purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community‐based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006–2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N‐cadherin, Keratin‐19, Lumican, CXCL6, RANTES, IL‐17, IL‐6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure‐pain threshold. The coefficients of variation were used to evaluate inter‐ and intra‐assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score‐matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL‐6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin‐19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027‐1037, 2020
Association between sleep and severe periodontitis in a nationally representative adult US population
Authors: Alqaderi Hend , Goodson J. Max , Agaku Israel 
Published: November 2019

AbstractBackgroundPoor sleep behavior appears to have adverse effects on health by metabolic disruption and immunity suppression. Sleep disturbance is strongly associated with diabetes, cardiovascular diseases, and some cancers. This study aimed to evaluate the association between sleep duration and periodontal disease in a national US population study in a National Health and Nutrition Examination Survey (NHANES).MethodsThe data were collected from individuals aged ≥30 years and included 3,624 participants in the United States NHANES 2013 to 2014. A weighted multivariable logistic regression modeling quantified the association between sleep and severe periodontal disease. We tested for diabetes as an effect modifier, adjusting for potential confounders such as smoking status, sex, age, education level, and dental visit.ResultsIndividuals who sleep >7 hours/night with no trouble sleeping are 40% less likely to have severe periodontal disease (odds ratio [OR] = 0.6, P < 0.05), adjusting for age, sex, smoking status, FPL, education level, and dental visit. Additionally, diabetes was a significant positive effect modifier of the relationship between sleep and severe periodontal disease (OR = 4.8, P < 0.05).ConclusionsFindings of this cross‐sectional representative study of an adult US population revealed a statistically significant association between sleep duration and severe periodontitis. In this study, individuals who slept >7 hours/night were less likely to exhibit severe periodontal disease. It also seems that this relationship was stronger among individuals with diabetes compared with individuals without diabetes.
Identification of Lower Pleistocene widespread tephras associated with large caldera‐forming eruptions in the Tohoku area, north‐east Japan
Authors: Suzuki Takehiko , Maruyama Seiji , Danhara Tohru , Hirata Takafumi , Machida Hiroshi , Arai Fusao 
Published: November 2019

ABSTRACTTephra fingerprinting techniques contributing to volcanology and palaeoenvironmental studies have been developed using a combination of laser‐ablation inductively coupled‐plasma mass spectrometry (LA‐ICP‐MS) and scanning electron microscopy with energy‐dispersive X‐ray spectroscopy (SEM‐EDS). In particular, femtosecond LA‐ICP‐MS can determine major‐ and trace element abundances in individual glass shards. On the basis of the major oxide and trace element composition of the glass shards, using those methods, we re‐examined the identification of four lower Pleistocene tephras originating from north‐east Japan. All trace element abundances exhibited the typical pattern of tephras from the Hokkaido–Tohoku area, and major element concentrations were distinct. As a result, we re‐examined the correlation of the widespread Tmg‐R4 tephra (2.0 Ma), and newly defined the widespread Kd44‐Naka tephra (1.968–1.781 Ma), both originating from the Sengan geothermal region. Furthermore, we re‐examined identifications of Sr‐Asn‐Kd8 (1.219 Ma) and Sr‐Kc‐U8 (0.922–0.910 Ma) in central Japan, both derived from the Aizu volcanic region. The extensive distributions of the former two tephras suggest the occurrence of two large caldera‐forming eruptions (Volcanic Explosivity Index 7) during a short period. Also, the distributions and volumes of the latter two tephras are broader and larger than those previously assumed. The results provide insight into large volcanic eruption history and terrestrial and marine palaeoenvironmental history.
Model for assessing organic light‐emitting diode display lifetime across applications
Authors: Miller Michael E. , Gerhardt Jérémie , Yoo Hyunjin , Akhavan Tara 
Published: November 2019

AbstractA model for assessing organic light‐emitting diode (OLED) display lifetime is developed and discussed for estimating OLED display lifetime in various applications. The lifetime model extends existing stretched exponential models of luminance decay for OLED devices to permit this decay to be estimated as a function of time and current density. This extended model is illustrated within an application to assess the power consumption and luminance decay of diodes within an OLED display. Various metrics of display lifetime are discussed with the aim of developing methods to assess the perceived lifetime of an OLED display to global and local luminance decay mechanisms. Finally, these metrics are applied to illustrate the performance of the model for assessing the impact of an image processing algorithm on OLED display lifetime.
Gas chromatography vacuum ultraviolet spectroscopy: A review
Authors: Lelevic Aleksandra , Souchon Vincent , Moreaud Maxime , Lorentz Chantal , Geantet Christophe 
Published: November 2019

AbstractAccelerated technological progress and increased complexity of interrogated matrices imposes a demand for fast, powerful, and resolutive analysis techniques. Gas chromatography has been for a long time a ‘go‐to’ technique for the analysis of mixtures of volatile and semi‐volatile compounds. Coupling of the several dimensions of gas chromatography separation has allowed to access a realm of improved separations in the terms of increased separation power and detection sensitivity. Especially comprehensive separations offer an insight into detailed sample composition for complex samples. Combining these advanced separation techniques with an informative detection system such as vacuum ultraviolet spectroscopy is therefore of great interest. Almost all molecules absorb the vacuum ultraviolet radiation and have distinct spectral features with compound classes exhibiting spectral signature similarities. Spectral information can be ‘filtered’ to extract the response in the most informative spectral ranges. Developed algorithms allow spectral mixture estimation of coeluting species. Vacuum ultraviolet detector follows Beer–Lambert law, with the possibility of calibrationless quantitation. The purpose of this article is to provide an overview of the features and specificities of gas chromatography–vacuum ultraviolet spectroscopy coupling which has gained interest since the recent introduction of a commercial vacuum ultraviolet detector. Potentials and limitations, relevant theoretical considerations, recent advances and applications are explored.
A low‐cost underwater particle tracking velocimetry system for measuring in situ particle flux and sedimentation rate in low‐turbulence environments
Authors: Simoncelli Stefano , Kirillin Georgiy , Tolomeev Aleksandr P. , Grossart Hans‐Peter 
Published: November 2019

AbstractWe describe a low‐cost three‐dimensional underwater particle tracking velocimetry system to directly measure particle settling rate and flux in low‐turbulence aquatic environments. The system consists of two waterproof cameras that acquire stereoscopic videos of sinking particles at 48 frames s−1 over a tunable sampling volume of about 45 × 25 × 24 cm. A dedicated software package has been developed to allow evaluation of particle velocities, concentration and flux, but also of morphometric parameters such as particle area, sinking angle, shape irregularity, and density. Our method offers several advantages over traditional approaches, like sediment trap or expensive in situ camera systems: (1) it does not require beforehand particle collection and handling; (2) it is not subjected to sediment trap biases from turbulence, horizontal advection, or presence of swimmers, that may alter particulate load and flux; (3) the camera system enables faster data processing and flux computation at higher spatial resolution; (4) apart from the particle settling rates, the particle size distribution, and morphology is determined. We tested the camera system in Lake Stechlin (Germany) in low turbulence and mean flow, and analyzed the morphological properties and settling rates of particles to determine their sinking behavior. The particle flux assessed from conventional sediment trap measurements agreed well with that determined by our system. By this, the low‐cost approach demonstrated its reliability in low turbulence environments and a strong potential to provide new insights into particulate carbon transport in aquatic systems. Extension of the method to more turbulent and advective conditions is also discussed.
Fast Ring‐Opening Polymerization of 1,2‐Disubstituted Epoxides Initiated by a CoIII‐Salen Complex
Authors: Liu Ye , Yu Hui Ying , Lu Xiao Bing 
Published: November 2019

AbstractPolyethers are an important class of polymers that find numerous applications. Ring‐opening polymerization of various 1,2‐disubstituted epoxides initiating a commercial, and well‐defined CoIII‐Salen complex is investigated in this paper. Remarkable reactivity (0.01% CoIII loadings, TOF up to 19200 h−1) is discovered in this transformation. High molecular weight polymers (up to 80 kg mol−1) are produced. In particular, polyether from ring‐opening polymerization of 1,4‐dihydronaphthalene oxide exhibits a glass transition temperatures (Tg) of up to 108 °C. By investigating the relationship between polymerization reactivity and counter ion in the CoIII complex, as well as the properties of the resultant polyethers, a cationic mechanism through an oxonium species is proposed.