bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental implant in a multiple myeloma patient undergoing bisphosphonate therapy: A case report
Authors: Bayani Mojtaba , Anooshirvani Ali Arash , Keivan Mohammad , Mohammad‐Rabei Elham
Published: April 2019

Dental implant placement in patients with multiple myeloma undergoing bisphosphonates therapy could be accomplished; however, it can turn into a successful treatment for edentulous area and functionally stabilized for many years. But a meticulous case selection, proper medical consultation with physician, minimally invasive surgery, and other cautions must be considered.
A rare case of follicular lymphoma transformed to a high‐grade B‐cell lymphoma in orbit
Authors: Vaddepally Raju K. , Hejab Amal , Dabak Vrushali , Menon Madhu
Published: April 2019

Key Clinical Message

Transformation of lymphoma is an infrequent phenomenon, and involvement of the eye as such is even uncommon. Histological transformation in patients with follicular lymphoma who were previously treated with immune‐chemotherapy carry a poor outcome. Here, we illustrate such a case with aggressive histological transformation from a low‐grade lymphoma.
Particular etiology in a case of peripheral tetraparesis
Authors: Gheorghe Gabriela S. , Hodorogea Andreea S. , Gheorghe Andrei C. D. , Zaharia Ondin I. R. , Neacsu Ovidiu , Nanea Ioan Tiberiu , Ciobanu Ana
Published: April 2019

Key Clinical Message

Lead intoxication is a rare but potentially fatal disease without appropriate intervention. The diagnosis is often difficult because of various organs involvement. We report the case of nonprofessional lead intoxication manifested by tetraparesis, severe anemia, and hemolysis in a patient having also unknown beta thalassemia minor.
Tracking of Particles in Froth Using Neutron Imaging
Authors: Heitkam Sascha , Lappan Tobias , Eckert Sven , Trtik Pavel , Eckert Kerstin
Published: April 2019

The movement of hydrophobic particles in a rising froth column is investigated. Gadolinium particles are hydrophobized and floated by means of small air bubbles. The generated froth is investigated by neutron imaging. Particles are identified by correlating the resulting radiographs with an artificial template of a typical particle and subsequent scanning for local maxima. The movement of the particles in the froth was analyzed for different froth stabilities, which resulted from various concentrations of the frother sodium oleate. Decreasing froth stability leads to lower superficial vertical particle velocity and to higher horizontal diffusion of particles due to bubble rupture.
Radioaktive Isotope des Wasserstoffs, Kohlenstoffs und Iods
Authors: Derdau Volker
Published: April 2019

Zusammenfassung und Ausblick

Radioaktiv markierte Wirkstoffe können auf unterschiedlichen Wegen hergestellt werden. Durch gezielte Versuche mit den markierten Substanzen lassen sich wichtige Hinweise über das Wirkungs‐ und Nebenwirkungsspektrum neu entwickelter Wirkstoffe gewinnen. Weiterhin werden nichtradioaktive Fluoreszenz‐ beziehungsweise Phosphoreszenzmarker weiterentwickelt. Diese sind vor allem in Screening‐Experimenten von Vorteil, verändern jedoch durch ihr Chromophor die Struktur der zu untersuchenden Substanz. In naher Zukunft wird man jedoch nicht auf den Einsatz radioaktiver „Sender“ verzichten können.
Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging
Authors: Konishi Takao , Sunaga Daisuke , Funayama Naohiro , Yamamoto Tadashi , Murakami Hironori , Hotta Daisuke , Nojima Masanori , Tanaka Shinya
Published: April 2019

Background

The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described.

Hypothesis

EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI.

Methods

Data on coronary artery plaques from 121 patients who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no‐EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI.

Results

We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low‐density lipoprotein cholesterol concentration, triglyceride concentration, and high‐density lipoprotein cholesterol concentration). OFDI data from 60 patients were analyzed in this study. The EPA group had significantly lower mean lipid index (818 ± 806 vs 1574 ± 891) and macrophage grade (13.5 ± 5.9 vs 19.3 ± 7.4) but higher mean minimum fibrous cap thickness (109.2 ± 55.7 vs 81.6 ± 36.4 μm) than the no‐EPA group (P = 0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P = 0.043 and 0.024, respectively).

Conclusion

This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.
Generation of ERK‐Independent Human and Non‐Human Primate Pluripotent Stem Cells
Authors: De Los Angeles Alejandro
Published: April 2019

The production of human organs inside human‐animal interspecies chimeras might one day comprise a viable strategy for generating patient‐specific organs, but such experiments will require human chimera‐competent pluripotent stem (PS) cells. The stabilization of PS cell self‐renewal in serum‐free medium and ERK blockade might be critical for capturing primate chimera‐competent pluripotency. It has recently been shown that shielding primate cells from the activation of ERK, WNT, and PKC signaling is crucial for deriving African green monkey ERK‐independent PS cells. Here, I show that this principle is generalizable to human cells. In this chapter, methods are provided to reset conventional human PS cells to ERK‐independence using histone deacetylase inhibitors and PGCX media comprised of N2B27 medium supplemented with LIF, PD0325901, Go6983, CHIR99021, and XAV939. The novel stem cells exhibit higher levels of KLF4 and manifest increased mitochondrial membrane depolarization. However, the author observed that not all PS cell lines are amenable to small molecule‐mediated resetting. The ERK‐independent PS cells described herein will provide a useful resource for testing interspecies organogenesis strategies. © 2019 by John Wiley & Sons, Inc.
Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout
Authors: Hill‐McManus Daniel , Marshall Scott , Soto Elena , Hughes Dyfrig A.
Published: April 2019

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality‐adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues. Compounds with reduced clearance or increased potency were more forgiving to missed doses, however, even following relatively large changes in these properties the predicted maximum reimbursement prices represented an increase of only 19% above febuxostat 80 mg. Linked pharmacometric and pharmacoeconomic modeling methods have the potential to inform early drug development by providing an indication of pricing options that may permit reimbursement.
Liver Microphysiological Systems for Predicting and Evaluating Drug Effects
Authors: Ribeiro Alexandre J. S. , Yang Xinning , Patel Vikram , Madabushi Rajnikanth , Strauss David G.
Published: April 2019

Liver plays a major role in drug metabolism and is one of the main sites of drug adverse effects. Microphysiological systems (MPS), also known as organs‐on‐a‐chip, are a class of microfluidic platforms that recreate properties of tissue microenvironments. Among different properties, the liver microenvironment is three‐dimensional, fluid flows around its cells, and different cell types regulate its function. Liver MPS aim to recreate these properties and enable drug testing and measurement of functional endpoints. Tests with these systems have demonstrated their potential for predicting clinical drug effects. Properties of liver MPS that improve the physiology of cell culture are reviewed, specifically focusing on the importance of recreating a physiological microenvironment to evaluate and model drug effects. Advances in modeling hepatic function by leveraging MPS are addressed, noting the need for standardization in the use, quality control, and interpretation of data from these systems.
Using a Benefit–Risk Analysis Approach to Capture Regulatory Decision Making: Melanoma
Authors: Raju G. K. , Gurumurthi Karthik , Domike Reuben , Theoret Marc R. , Pazdur Richard , Woodcock Janet
Published: April 2019

Drug regulators seek to make decisions regarding drug approvals based on analysis of the relevant benefits and risks. In this work, 25 US Food and Drug Administration (FDA) decisions on melanoma drugs were identified and analyzed based on clinical trial results published between 1999 and 2017. In each case, the benefits and risks of the new drug in each clinical trial relative to a comparator (typically the control arm of the same clinical trial) were quantified. The benefits and risks were analyzed using a common scale to allow for direct comparison. A sensitivity analysis was conducted using vemurafenib to explore the magnitude of uncertainty in the quantitative assessments. The associated FDA decision outcomes of the new drugs were consistent with the benefits and risks quantified in this work.
Extended artificial immune system–based optimized access control for big data on a cloud environment
Authors: Muneeshwari P. , Athisha G.
Published: April 2019

Integrating parallel computing and distributed computing together can be obtained by cloud computing (CC). One of the major problems faced by public CC is security regarding data access control. CC permits people to share data, documents, videos, and other types of data. Generally, the cloud data are considered as big data, because the volume of the data is huge and it has a greater number of varieties. In recent days, attribute‐based data sharing applied only for selected data is a crucial problem. One of the existing approaches encrypts data using various kinds of keys based on several types of cryptosystems. However, those kinds of methods have some weaknesses such as inability to handle the attributes effectively, storage of more unwanted copies of the same data, and policy changes. It needs a high amount of computational cost and reduces the efficiency of memory utilization and the computational speed. This paper motivated to design and implement an efficient approach for optimized access control (OAC) for data stored in the cloud to overcome these kinds of issues. The efficiency of the proposed method is proved through a simulation‐based experiment in Cloud Simulator.
Investigation of the distortion factor for Bussgang noise cancellation iterative receivers
Authors: Bibi Nargis , Muhammad Nazeer , Cheetham Barry
Published: April 2019

Orthogonal frequency‐division multiplexing (OFDM) is considered an efficient modulation approach in the field of wireless systems. However, the significant high peak to average power ratios (PAPR) are one of the prominant shortcomings of the OFDM systems leading to severe signal distortions and acute power inefficiency. Iterative receivers, which use Bussgang algorithm approach along with clipping at the transmitter, have been presented in the literature. This methodology is majorly receiver based in order to compensate the effects of the clipping noise that was added at the transmitter. These receivers are used to analyse the distortions of clipping noise directly subtracting from the signals that are received in order to get the original signal. We demonstrate in this study a detailed and technical investigation of the Bussgang noise cancellation (BNC) receiver along with some significant results. Simulation results are presented to show that the BNC iterative receiver does not estimate the accurate clipping noise, and the performance may be improved if at the receiver end, it is somehow capable to analyze the precise clipping noise for each OFDM signal.
The role of sensory innervation in cornea‐lens regeneration
Authors: Perry Kimberly J. , Hamilton Paul W. , Sonam Surabhi , Singh Ratnakar , Henry Jonathan J.
Published: April 2019

Background

Numerous sensory nerves in the cornea contribute to normal tissue homeostasis. Interestingly, cells within the basal corneal epithelium can regenerate new lenses in the frog, Xenopus. In this study, we investigated whether cornea sensory nerves or their neuropeptides are important for supporting cornea‐lens regeneration.

Results

Attempts to sever the trigeminal nerve trunk, which provides sensory nerve branches to the cornea, did not inhibit lens regeneration. However, using this approach we found that it was not possible to completely disrupt sensory innervation, as these nerves are able to quickly regenerate back to the cornea. On the other hand, attenuation of neuropeptide levels with capsaicin was found to significantly inhibit lens regeneration, as visualized by a reduction of Substance P. These treatments also led to a reduction of cornea sensory innervation. Interestingly, inhibition of the Substance P‐preferred receptor NK‐1 with Spantide II did not affect lens‐regeneration rates.

Conclusions

This study provides evidence that cornea nerves support cornea‐lens regeneration, which could occur through the release of various neurotrophic factors. Substance P, however, does not appear to be the critical component of this signaling pathway. Further studies are needed to investigate what role other known neurotrophic factors may play in this process.
North‐facing slopes and elevation shape asymmetric genetic structure in the range‐restricted salamander Plethodon shenandoah
Authors: Mulder Kevin P. , Cortes‐Rodriguez Nandadevi , Campbell Grant Evan H. , Brand Adrianne , Fleischer Robert C.
Published: April 2019

Species with narrow environmental tolerances are often distributed within fragmented patches of suitable habitat, and dispersal among these subpopulations can be difficult to directly observe. Genetic data can help quantify gene flow between localities, which is especially important for vulnerable species with a disjunct range. The Shenandoah salamander (Plethodon shenandoah) is a federally endangered species known only from three mountaintops in Virginia, USA. To reconstruct the evolutionary history and population connectivity of this species, we generated both mitochondrial and nuclear data using sequence capture from individuals collected across all three mountaintops. Applying population and landscape genetic methods, we found strong population structure that was independent of geographic distance. Both the nuclear markers and mitochondrial genomes indicated a deep split between the most southern population and the genetically similar central and northern populations. Although there was some mitochondrial haplotype‐splitting between the central and northern populations, there was admixture in nuclear markers. This is indicative of either a recent split or current male‐biased dispersal among mountain isolates. Models of landscape resistance found that dispersal across north‐facing slopes at mid‐elevation levels best explain the observed genetic structure among populations. These unexpected results highlight the importance of incorporating landscape features in understanding and predicting the movement and fragmentation of this range‐restricted salamander species across space.
Breeding latitude predicts timing but not rate of spring migration in a widespread migratory bird in South America
Authors: Jahn Alex E. , Cereghetti Joaquín , Cueto Víctor R. , Hallworth Michael T. , Levey Douglas J. , Marini Miguel Â. , Masson Diego , Pizo Marco A. , Sarasola José Hernán , Tuero Diego T.
Published: April 2019

Identifying the processes that determine avian migratory strategies in different environmental contexts is imperative to understanding the constraints to survival and reproduction faced by migratory birds across the planet.

We compared the spring migration strategies of Fork‐tailed Flycatchers (Tyrannus s. savana) that breed at south‐temperate latitudes (i.e., austral migrants) vs. tropical latitudes (i.e., intratropical migrants) in South America. We hypothesized that austral migrant flycatchers are more time‐selected than intratropical migrants during spring migration. As such, we predicted that austral migrants, which migrate further than intratropical migrants, will migrate at a faster rate and that the rate of migration for austral migrants will be positively correlated with the onset of spring migration.

We attached light‐level geolocators to Fork‐tailed Flycatchers at two tropical breeding sites in Brazil and at two south‐temperate breeding sites in Argentina and tracked their movements until the following breeding season.

Of 286 geolocators that were deployed, 37 were recovered ~1 year later, of which 28 provided useable data. Rate of spring migration did not differ significantly between the two groups, and only at one site was there a significantly positive relationship between date of initiation of spring migration and arrival date.

This represents the first comparison of individual migratory strategies among conspecific passerines breeding at tropical vs. temperate latitudes and suggests that austral migrant Fork‐tailed Flycatchers in South America are not more time‐selected on spring migration than intratropical migrant conspecifics. Low sample sizes could have diminished our power to detect differences (e.g., between sexes), such that further research into the mechanisms underpinning migratory strategies in this poorly understood system is necessary.
Genetic turnovers and northern survival during the last glacial maximum in European brown bears
Authors: Ersmark Erik , Baryshnikov Gennady , Higham Thomas , Argant Alain , Castaños Pedro , Döppes Doris , Gasparik Mihaly , Germonpré Mietje , Lidén Kerstin , Lipecki Grzegorz , Marciszak Adrian , Miller Rebecca , Moreno‐García Marta , Pacher Martina , Robu Marius , Rodriguez‐Varela Ricardo , Rojo Guerra Manuel , Sabol Martin , Spassov Nikolai , Storå Jan , Valdiosera Christina , Villaluenga Aritza , Stewart John R. , Dalén Love
Published: April 2019

The current phylogeographic pattern of European brown bears (Ursus arctos) has commonly been explained by postglacial recolonization out of geographically distinct refugia in southern Europe, a pattern well in accordance with the expansion/contraction model. Studies of ancient DNA from brown bear remains have questioned this pattern, but have failed to explain the glacial distribution of mitochondrial brown bear clades and their subsequent expansion across the European continent. We here present 136 new mitochondrial sequences generated from 346 remains from Europe, ranging in age between the Late Pleistocene and historical times. The genetic data show a high Late Pleistocene diversity across the continent and challenge the strict confinement of bears to traditional southern refugia during the last glacial maximum (LGM). The mitochondrial data further suggest a genetic turnover just before this time, as well as a steep demographic decline starting in the mid‐Holocene. Levels of stable nitrogen isotopes from the remains confirm a previously proposed shift toward increasing herbivory around the LGM in Europe. Overall, these results suggest that in addition to climate, anthropogenic impact and inter‐specific competition may have had more important effects on the brown bear's ecology, demography, and genetic structure than previously thought.
Long‐term population dynamics of dreissenid mussels (Dreissena polymorpha and D. rostriformis): a cross‐system analysis
Authors: Strayer David L. , Adamovich Boris V. , Adrian Rita , Aldridge David C. , Balogh Csilla , Burlakova Lyubov E. , Fried‐Petersen Hannah B. , G.‐Tóth László , Hetherington Amy L. , Jones Thomas S. , Karatayev Alexander Y. , Madill Jacqueline B. , Makarevich Oleg A. , Marsden J. Ellen , Martel André L. , Minchin Dan , Nalepa Thomas F. , Noordhuis Ruurd , Robinson Timothy J. , Rudstam Lars G. , Schwalb Astrid N. , Smith David R. , Steinman Alan D. , Jeschke Jonathan M.
Published: April 2019

Dreissenid mussels (including the zebra mussel Dreissena polymorpha and the quagga mussel D. rostriformis) are among the world's most notorious invasive species, with large and widespread ecological and economic effects. However, their long‐term population dynamics are poorly known, even though these dynamics are critical to determining impacts and effective management. We gathered and analyzed 67 long‐term (>10 yr) data sets on dreissenid populations from lakes and rivers across Europe and North America. We addressed five questions: (1) How do Dreissena populations change through time? (2) Specifically, do Dreissena populations decline substantially after an initial outbreak phase? (3) Do different measures of population performance (biomass or density of settled animals, veliger density, recruitment of young) follow the same patterns through time? (4) How do the numbers or biomass of zebra mussels or of both species combined change after the quagga mussel arrives? (5) How does body size change over time? We also considered whether current data on long‐term dynamics of Dreissena populations are adequate for science and management. Individual Dreissena populations showed a wide range of temporal dynamics, but we could detect only two general patterns that applied across many populations: (1) Populations of both species increased rapidly in the first 1–2 yr after appearance, and (2) quagga mussels appeared later than zebra mussels and usually quickly caused large declines in zebra mussel populations. We found little evidence that combined Dreissena populations declined over the long term. Different measures of population performance were not congruent; the temporal dynamics of one life stage or population attribute cannot generally be accurately inferred from the dynamics of another. We found no consistent patterns in the long‐term dynamics of body size. The long‐term dynamics of Dreissena populations probably are driven by the ecological characteristics (e.g., predation, nutrient inputs, water temperature) and their temporal changes at individual sites rather than following a generalized time course that applies across many sites. Existing long‐term data sets on dreissenid populations, although clearly valuable, are inadequate to meet research and management needs. Data sets could be improved by standardizing sampling designs and methods, routinely collecting more variables, and increasing support.
Mathematical modeling and sensitivity analysis of xylene removal in a scoria‐compost biofilter
Authors: Heidari Mohsen , Rahimi Amir , Amin Mohammad M. , Bina Bijan , Sami Samaneh , Nourmoradi Heshmatollah , Mohammadi‐moghadam Fazel , Norouzi Samira
Published: April 2019

Mathematical modeling of biofiltration systems improves our understanding and design of such complex systems. This study focused on the theoretical and technical aspects of the modeling of xylene biofiltration in the absence and presence of a nonionic surfactant. In this regard, a mathematical model was developed based on mass balance principles in gas and biofilm phases. The developed model was calibrated and validated using the experimental data obtained from a lab‐scale scoria‐compost biofilter, which operated for 151 days in the absence and presence of Tween‐20, a nonionic surfactant. First, the model was calibrated using the experimental data obtained at empty bed retention time (EBRT) of 90 s and then validated with the data obtained at two other EBRTs. The biofilter provided maximum elimination capacities (ECmax) of 97.5 and 93.6 g m−3 hr−1, respectively, in the absence and presence of the surfactant at EBRT of 90 s. The corresponding predicted ECmax values were 99.9 and 95.7 g m−3 hr−1, respectively. Both model output and experimental data revealed that the nonionic surfactant improved the performance of the biofilter at moderate inlet loading rates. Various statistical measures, including fractional bias, average absolute relative error, and coefficient of determination (R2), showed good agreement between experimental data and estimated model predictions. Sensitivity analysis of the model showed that the specific surface area and bioreactor length affected strongly the results of the model. In general, the results of this study would in turn form the design basis for engineering purposes.
Evaluation of elastic property changes in Karamay oil sand reservoir during thermal stimulation
Authors: Pang Huiwen , Jin Yan , Gao Yanfang
Published: April 2019

To obtain a good evaluation of oil sand reservoir deformation and its induced ground subsidence during thermal simulation, elastic property changes with reservoir temperature are desired. The Karamay oil sand was viewed as a composite geomaterial consisting of bitumen as matrix and grains as inclusion. The elastic properties of bitumen were expressed as a function of temperature and time, and the Eshelby, Mori–Tanaka, and differential methods were used to write the elastic properties of oil sand as a function of temperature and time. An equivalent static time was proposed to eliminate the effect of time. A temperature transform was established according to experimental data. The relation of elastic properties and temperature was applied on a field practice of steam circulation. The elastic properties in any reservoir position were given at varying circulation time and concluded that the elastic modulus drops from 663 to 360 MPa, and the Poisson ratio increases from 0.3 to 0.415 during circulation. The elastic deformation mechanisms for Karamay sand‐in‐bitumen and Canadian bitumen‐in‐sand oil sands were analyzed according to experimental data. Three possible deformation modes for sand‐in‐bitumen oil sands were exhibited, considering whether the intergranular bitumen is squeezed out and the grains are crushed.
Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes
Authors: Ganster Christina , Müller‐Thomas Catharina , Haferlach Claudia , Strupp Corinna , Ogata Kiyoyuki , Germing Ulrich , Hildebrandt Barbara , Mallo Mar , Lübbert Michael , Müller Christel , Solé Francesc , Götze Katharina S. , Vandenberghe Peter , Göhring Gudrun , Steinmetz Tilman , Kröger Nicolaus , Platzbecker Uwe , Söling Ulrike , Raynaud Sophie , Shirneshan Katayoon , Schanz Julie , Haase Detlef
Published: April 2019

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.
IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?
Authors: Kanagalingam Tharsan , Solomon Lauren , Vijeyakumaran Meerah , Palikhe Nami Shrestha , Vliagoftis Harissios , Cameron Lisa
Published: April 2019

Background

Glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine expression and induce apoptosis. Asthma severity is associated with type 2 inflammation, circulating Th2 cells and higher GC requirements.

Objective

The aim of this study was to assess whether ex vivo production of interleukin 2 (IL‐2), a T‐cell survival factor, associated with clinical features of asthma severity, the proportion of blood Th2 cells and Th2 cell responses to GC.

Methods

Peripheral blood from asthma patients (n = 18) was obtained and the proportion of Th2 cells determined by flow cytometry. Peripheral blood cells were activated with mitogen (24 hours) and supernatant levels of IL‐2 and IL‐13 measured by enzyme‐linked immunosorbent assay. In vitro differentiated Th2 cells were treated with dexamethasone (DEX) and IL‐2 and assessed for apoptosis by flow cytometry (annexin V). Level of messenger RNA (mRNA) for antiapoptotic (BCL‐2) and proapoptotic (BIM) genes, IL‐13, GC receptor (GR) and FKBP5 were determined by quantitative real‐time polymerase chain reaction. GR binding was assessed by chromatin immunoprecipitation.

Results

IL‐2 produced by activated peripheral blood cells correlated negatively with lung function and positively with a daily dose of inhaled GC. When patients were stratified based on IL‐2 level, high IL‐2 producers made more IL‐13 and had a higher proportion of circulating Th2 cells. In vitro, increasing the level of IL‐2 in the culture media was associated with resistance to DEX‐induced apoptosis, with more BCL‐2/less BIM mRNA. Th2 cells cultured in high IL‐2 had more IL‐13, less GR mRNA, showed reduced binding of the GR to FKBP5, a known GC‐induced gene, and required higher concentrations of DEX for cytokine suppression.

Conclusions and Clinical Relevance

IL‐2 downregulates Th2 cell responses to GC, supporting both their survival and pro‐inflammatory capacity. These results suggest that a patient's potential to produce IL‐2 may be a determinant in asthma severity.
Loss of the Vitamin D Receptor in Human Breast Cancer Cells Promotes Epithelial to Mesenchymal Cell Transition and Skeletal Colonization
Authors: Horas Konstantin , Zheng Yu , Fong-Yee Colette , Macfarlane Eugenie , Manibo Jeline , Chen Yunzhao , Qiao Jeremy , Gao Mingxuan , Haydar Nancy , McDonald Michelle M , Croucher Peter I , Zhou Hong , Seibel Markus J
Published: April 2019

Expression of the vitamin D receptor (VDR) is thought to be associated with neoplastic progression. However, the role of the VDR in breast cancer metastasis to bone and the molecular mechanisms underlying this process are unknown. Employing a rodent model (female Balb/c nu/nu mice) of systemic metastasis, we here demonstrate that knockdown of the VDR strongly increases the metastatic potential of MDA-MB-231 human breast cancer cells to bone, resulting in significantly greater skeletal tumor burden. Ablation of VDR expression promotes cancer cell mobility (migration) and invasiveness, thereby facilitating skeletal colonization. Mechanistically, these changes in tumor cell behavior are attributable to shifts in the expression of proteins involved in cell adhesion, proliferation, and cytoskeletal organization, patterns characteristic for epithelial-to-mesenchymal cell transition (EMT). In keeping with these experimental findings, analyses of human breast cancer specimens corroborated the association between VDR expression, EMT-typical changes in protein expression patterns, and clinical prognosis. Loss of the VDR in human breast cancer cells marks a critical point in oncogenesis by inducing EMT, promoting the dissemination of cancer cells, and facilitating the formation of tumor colonies in bone. © 2019 American Society for Bone and Mineral Research.
Potential Technologies Review: A hybrid information retrieval framework to accelerate demand‐pull innovation in biomedical engineering
Authors: Schmitz Tom , Bukowski Mark , Koschmieder Steffen , Schmitz‐Rode Thomas , Farkas Robert
Published: April 2019

Launching biomedical innovations based on clinical demands instead of translating basic research findings to practice reduces the risk that the results will not fit the clinical routine. To realize this type of innovation, a meta‐analysis of the body of research is necessary to reveal demand‐matching concepts. However, both the data deluge and the narrow time constraints for innovation make it impossible to perform such reviews manually. Thus, this paper proposes a specifically adapted “Potential Technologies Review” approach focusing on automated text mining and information retrieval techniques. The novel framework combines features from both systematic and scoping reviews. It aims at high coverage and reproducibility while mapping technologies—even with a fuzzy initial scope. To achieve these goals for search and triage, a set of closely interrelated methods has been developed: (a) automated query optimization, (b) screening prioritization, and (c) recall estimation. To determine appropriate parameters, a variety of published literature corpora were used and compared with an evaluation on a real‐world dataset. Our results show that it is feasible to automate the identification of relevant works using this newly introduced framework. It achieved a workload reduction of up to 91% “Work‐saved‐over Sampling (WSS)” with a 76% overall recall compared with manually screening search results. Reducing the workload is a prerequisite for a rapid Potential Technologies Review when conducting demand‐pull innovations. Moreover, it facilitates the updating and closer monitoring of latest findings. Studying the robustness of the framework and expanding it to patent documents are future tasks.
Identification of novel mutations in preaxial polydactyly patients through whole‐exome sequencing
Authors: Wang Tao , Xuan Zhaopeng , Dou Yichen , Liu Yang , Fu Yanyan , Ren Jingyan , Lu Laijin
Published: April 2019

Background

Polydactyly is one of the most common hereditary limb malformation characterized by additional digits in hands and/or feet. With extra fingers/toes, which could be very problematic, polydactyly patients are usually treated in early childhood by removing of extra digits with surgery. Genetically, polydactyly is caused by mutations of genes that involve in digit formation.

Methods

In the current report, we performed genetic analysis for polydactyly using DNA samples from a cohort of 20 Chinese patients. All patients show preaxial polydactyly in one of their hands.

Results

With whole‐exome sequencing (WES), we have identified two novel heterozygous mutations c.G2844A in GLI3 gene (OMIM 165240) and c.1409_1410del in EVC gene (OMIM 604831). Compound heterozygous mutations that affect KIAA0586 gene (OMIM 610178) are also detected. Proteins encoded by the genes have important roles in primary cilia and regulate sonic hedgehog signaling pathway.

Conclusion

Our study highlights the important roles of primary cilia in limb development, and helps to further understand the molecular mechanisms for polydactyly formation.
The Year Ahead
Authors: Dickson Glen
Published: April 2019

What can we expect from the display industry in 2019? Top market analysts offer their insights and highlight a few key trends worth following.
A First Look at Display Week 2019
Authors: Donelan Jenny
Published: April 2019

What can you expect from Display Week, the Society for Information Display's annual conference? Now in its 56th year, it offers many of the signature features that the display community has come to expect, as well as new presentation tracks, new programs, and new opportunities to network. Here's a sneak peek at the event.
Some properties of transportation network cooperative games
Authors: Gnecco Giorgio , Hadas Yuval , Sanguineti Marcello
Published: April 2019

A basic question in network analysis concerns the quantification of the importance of each node in terms of network connectivity. To this end, a possible approach consists in using cooperative game theory tools to define a measure of node centrality. In this paper, given a transportation network, a cooperative game model with transferable utility (TU game) is considered. The nodes of the network represent the players in such a game, and the Shapley values of the nodes are used to measure centrality. The model, called Transportation Network cooperative (TNc) game, integrates within the utility function of the TU game the network topology and the demand. Properties of TNc games and their associated utility functions are investigated. Numerical results are reported, to get insights into the obtained properties.
Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations
Authors: Khani Francesca , Wobker Sara E , Hicks Jessica L , Robinson Brian D , Barbieri Christopher E , De Marzo Angelo M , Epstein Jonathan I , Pritchard Colin C , Lotan Tamara L
Published: April 2019

Intraductal carcinoma of the prostate (IDC‐P) most often appears associated with high‐grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC‐P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low‐grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC‐P (iIDC‐P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC‐P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC‐P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC‐P alterations were similar to those previously described in high‐grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC‐P (BRCA2, CHEK2, CDK12) and other known PCa‐associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC‐P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC‐P and the low‐grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC‐P in four. Despite a CNA profile similar to conventional PCa, iIDC‐P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC‐P is not likely a precursor to the associated low‐grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Limitations for health research with restricted data collection from UK primary care
Authors: Strongman Helen , Williams Rachael , Meeraus Wilhelmine , Murray‐Thomas Tarita , Campbell Jennifer , Carty Lucy , Dedman Daniel , Gallagher Arlene M. , Oyinlola Jessie , Kousoulis Antonis , Valentine Janet
Published: April 2019

Purpose

UK primary care provides a rich data source for research. The impact of proposed data collection restrictions is unknown. This study aimed to assess the impact of restricting the scope of electronic health record (EHR) data collection on the ability to conduct research. The study estimated the consequences of restricted data collection on published Clinical Practice Research Datalink studies from high impact journals or referenced in clinical guidelines.

Methods

A structured form was used to systematically analyse the extent to which individual studies would have been possible using a database with data collection restrictions in place: (1) retrospective collection of specified diseases only; (2) retrospective collection restricted to a 6‐ or 12‐year period; (3) prospective and retrospective collection restricted to non‐sensitive data. Outcomes were categorised as unfeasible (not reproducible without major bias); compromised (feasible with design modification); or unaffected.

Results

Overall, 91% studies were compromised with all restrictions in place; 56% studies were unfeasible even with design modification. With restrictions on diseases alone, 74% studies were compromised; 51% were unfeasible. Restricting collection to 6/12 years had a major impact, with 67 and 22% of studies compromised, respectively. Restricting collection of sensitive data had a lesser but marked impact with 10% studies compromised.

Conclusion

EHR data collection restrictions can profoundly reduce the capacity for public health research that underpins evidence‐based medicine and clinical guidance. National initiatives seeking to collect EHRs should consider the implications of restricting data collection on the ability to address vital public health questions.
An Anisotropic Elastoviscoplasticity Model of Thermomechanical Responses of Shocked β‐HMX and α‐RDX Single Crystals
Authors: Wang XinJie , Wu YanQing , Huang FengLei , Hu WeiJia , Liu YuCun
Published: April 2019

An anisotropic elastoviscoplasticity constitutive model for β‐cyclotetramethylene tetranitramine (β‐HMX) and α‐cyclotrimethylene trinitramine single crystals (α‐RDX) is developed to analyze the thermomechanical responses under shock loading. The model considers nonlinear, pressure and temperature dependent elasticity, and dislocation‐based plasticity which incorporate regenerative multiplication and heterogeneous nucleation mechanisms. The proposed model is calibrated against experimental wave profiles of (011), (010), (100),
,
and
orientations of HMX single crystals and (210), (100),
,
and (111) orientations of RDX single crystals. The model can well capture elastoplastic double wave structure, stress relaxation after the Hugoniot elastic limit as well as the arrival of plastic wave. Moreover, pressure, accumulated shear strain, and temperature contours of both HMX and RDX show obvious anisotropy and non‐uniform spatial distribution, which is explained by analyzing dislocation activity with corresponding resolved shear stress on slip systems. Results provide insights into understanding ignition mechanisms and predicting ignition sensitivity of explosive single crystals as well as polymer bonded explosives at the mesoscale.
Translation‐coupled protein folding assay using a protease to monitor the folding status
Authors: Niwa Tatsuya , Uemura Eri , Matsuno Yuki , Taguchi Hideki
Published: April 2019

Protein folding is an essential prerequisite for proteins to execute nearly all cellular functions. There is a growing demand for a simple and robust method to investigate protein folding on a large‐scale under the same conditions. We previously developed a global folding assay system, in which proteins translated using an Escherichia coli‐based cell‐free translation system are centrifuged to quantitate the supernatant fractions. Although the assay is based on the assumption that the supernatants contain the folded native states, the supernatants also include nonnative unstructured proteins. In general, proteases recognize and degrade unstructured proteins, and thus we used a protease to digest the unstructured regions to monitor the folding status. The addition of Lon protease during the translation of proteins unmasked subfractions, not only in the soluble fractions but also in the aggregation‐prone fractions. We translated ∼90 E. coli proteins in the protease‐inclusion assay, in the absence and presence of chaperones. The folding assay, which sheds light on the molecular mechanisms underlying the aggregate formation and the chaperone effects, can be applied to a large‐scale analysis.
M‐Branes: Lessons from M2's and Hopes for M5's
Authors: Lambert Neil
Published: April 2019

In this talk we will review the construction of M2‐brane SCFT's highlighting some novelties and the role of 3‐algebras. Parts of our discussion will closely follow parts of [1]. Next we will discuss M5‐branes: the basics, the obstacles as well as various attempts to construct the associated SCFT and potential relations between M2‐branes and M5‐branes.
Role of iron in cancer development by viruses
Authors: Shoja Zabihollah , Chenari Maryam , Jafarpour Ali , Jalilvand Somayeh
Published: April 2019

Increased levels of iron in body are attributed to higher cancer risk. Given the fact that 16% of all human cancers are caused by viral infections, iron is suggested to play an important role in carcinogenesis particularly those induced by viral infections. The present study provides an updated summary of the literature and the plausible mechanisms of iron involvement in cancer development by viruses. Our understanding about the interplay between viral infections and iron in different settings particularly cancer development is yet to be improved as it may shed a new light in development of new therapeutic strategies.
Gain insight into supporting student‐athletes’ transition to life after graduation
Authors: McCarthy Claudine
Published: April 2019

BOSTON — From higher rates of academic adjustment, institutional attachment, and graduation to lower levels of loneliness and a more positive overall experience, the statistics paint a very positive picture of college student‐athletes on campus.
Ultrafine Ru/RuOx Nanoparticles Uniformly Anchored on Carbon Nanotubes as Cathode Electrocatalyst for Lithium‐Oxygen Batteries
Authors: Zhang Yaowen , Wang Xiaogang , Yin Jianjun , Wang Yifeng , Li Chao , Xia Dingguo
Published: April 2019

The nonaqueous lithium‐oxygen (Li‐O2) battery possesses extremely high theoretical energy density which is considered as one of the most fascinating next‐generation energy storage systems. However, the sluggish oxygen redox reaction kinetics in the cathode of Li‐O2 battery severely limits its practical application. The incorporation of cathode electrocatalyst with high activity is an effective strategy to address this issue. Herein we report a novel electrocatalyst of ultrafine Ru/RuOx nanoparticles (NPs) decorated on the surface of carbon nanotubes (Ru/RuOx@CNTs) synthesized by a facile modified ethylene glycol reduction method. The as‐prepared Ru/RuOx@CNTs electrocatalyst as cathode for Li‐O2 battery delivers high initial discharge specific capacity up to 3795 mAh g−1, low overpotential and preferable cycle stability of 113 cycles with a limited specific capacity of 500 mAh g−1 at 0.1 mA cm−2 compared with CNTs cathode, which is originated from the well‐dispersed Ru/RuOx nanoparticles on CNTs, leading to efficient electrocatalytic activities for oxygen reduction and evolution reactions.