bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Health Care Costs and Improved Appropriateness of Incoming Test Orders: the Impact of Genetic Counselor Review in an Academic Genetic Testing Laboratory
Authors: Wakefield Emily , Keller Haley , Mianzo Hannah , Nagaraj Chinmayee B. , Tawde Sanjukta , Ulm Elizabeth 
Published: February 2018

AbstractThe goal of this study was to evaluate the impact of genetic counselor (GC) review of incoming test orders received in an academic diagnostic molecular genetics laboratory. The GC team measured the proportion of orders that could be modified to improve efficiency or sensitivity, tracked provider uptake of GC proposed testing changes, and calculated the health care dollar savings resulting from GC intervention. During this 6‐month study, the GC team reviewed 2367 incoming test orders. Of these, 109 orders (4.6%) were flagged for review for potentially inefficient or inappropriate test ordering. These flagged orders corresponded to a total of 51 cases (1–5 orders for each patient), representing 54 individuals and including 3 sibling pairs. The GC team proposed a modification for each flagged case and the ordering providers approved the proposed change for 49 of 51 cases (96.08%). For the 49 modifications, the cost savings totaled $98,750.64, for an average of $2015.32 saved per modification. This study provides evidence of the significant contribution of genetic counselors in a laboratory setting and demonstrates the benefit of laboratories working with ordering providers to identify the best test for their patients. The review of test orders by a genetic counselor both improves genetic test ordering strategies and decreases the amount of health care dollars spent on genetic testing.
Local microstructure-based material performance and damage in design and finite element simulations of cast components
Authors: Olofsson Jakob 
Published: February 2018

AbstractA novel approach to incorporate local microstructure-based material performance into finite element method (FEM) simulations of cast components is presented. By adopting perspectives from natural designs as dinosaur skulls and trees, the discipline-wide approach enables accurate prediction of damage in structures based on a heterogeneous distribution of sub-scale features. It is shown that heterogeneous damage tolerance dictates the performance and failure of cast aluminum, and simulations are compared with experimental results of heterogeneous tensile samples using digital image correlation (DIC). The numerical application of the approach in the industrial product realization process of an industrial casting is demonstrated, and the applicability of the approach to understand the behavior and failure of natural as well as synthetic structures is discussed.Highlights A new discipline-wide approach to predict failure of heterogeneous structures. Based on natural designs, the approach enables tailored performance of castings. Heterogeneous damage tolerance reveal fracture and enables damage tolerant designs. The approach is implemented into numerical casting and load simulations. Future pathways to design high performing castings are explored.
Non-contact mechanical and chemical analysis of single living cells by microspectroscopic techniques
Authors: Mattana Sara , Mattarelli Maurizio , Urbanelli Lorena , Sagini Krizia , Emiliani Carla , Serra Mauro Dalla , Fioretto Daniele , Caponi Silvia 
Published: February 2018

AbstractInnovative label-free microspectroscopy, which can simultaneously collect Brillouin and Raman signals, is used to characterize the viscoelastic properties and chemical composition of living cells with sub-micrometric resolution. The unprecedented statistical accuracy of the data combined with the high-frequency resolution and the high contrast of the recently built experimental setup permits the study of single living cells immersed in their buffer solution by contactless measurements. The Brillouin signal is deconvoluted in the buffer and the cell components, thereby revealing the mechanical heterogeneity inside the cell. In particular, a 20% increase is observed in the elastic modulus passing from the plasmatic membrane to the nucleus as distinguished by comparison with the Raman spectroscopic marker. Brillouin line shape analysis is even more relevant for the comparison of cells under physiological and pathological conditions. Following oncogene expression, cells show an overall reduction in the elastic modulus (15%) and apparent viscosity (50%). In a proof-of-principle experiment, the ability of this spectroscopic technique to characterize subcellular compartments and distinguish cell status was successfully tested. The results strongly support the future application of this technique for fundamental issues in the biomedical field.
The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion
Authors: Barbui Tiziano , Thiele Jürgen , Gisslinger Heinz , Kvasnicka Hans Michael , Vannucchi Alessandro M. , Guglielmelli Paola , Orazi Attilio , Tefferi Ayalew 
Published: February 2018

AbstractThe new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. In this regard, the 2016 changes were aimed at facilitating the distinction between masked PV and JAK2-mutated ET and between prefibrotic/early and overtly fibrotic PMF. In the current communication, we (i) provide practically useful resource tables and graphs on the new diagnostic criteria including outcome, (ii) elaborate on the rationale for the 2016 changes, (iii) discuss the complementary role of mutation screening, (iv) address ongoing controversies and propose solutions, (v) attend to the challenges of applying WHO criteria in routine clinical practice, and (vi) outline future directions from the perspectives of the clinical pathologist.
Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
Authors: Darlington Alexander P. S. , Kim Juhyun , Jiménez José I. , Bates Declan G. 
Published: February 2018

AbstractIntroduction of synthetic circuits into microbes creates competition between circuit and host genes for shared cellular resources, such as ribosomes. This can lead to the emergence of unwanted coupling between the expression of different circuit genes, complicating the design process and potentially leading to circuit failure. By expressing a synthetic 16S rRNA with altered specificity, we can partition the ribosome pool into host-specific and circuit-specific activities. We show mathematically and experimentally that the effects of resource competition can be alleviated by targeting genes to different ribosomal pools. This division of labour can be used to increase flux through a metabolic pathway. We develop a model of cell physiology which is able to capture these observations and use it to design a dynamic resource allocation controller. When implemented, this controller acts to decouple genes by increasing orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases.
A community approach to mortality prediction in sepsis via gene expression analysis
Authors: Sweeney Timothy E. , Perumal Thanneer M. , Henao Ricardo , Nichols Marshall , Howrylak Judith A. , Choi Augustine M. , Bermejo-Martin Jesús F. , Almansa Raquel , Tamayo Eduardo , Davenport Emma E. , Burnham Katie L. , Hinds Charles J. , Knight Julian C. , Woods Christopher W. , Kingsmore Stephen F. , Ginsburg Geoffrey S. , Wong Hector R. , Parnell Grant P. , Tang Benjamin , Moldawer Lyle L. , Moore Frederick E. , Omberg Larsson , Khatri Purvesh , Tsalik Ephraim L. , Mangravite Lara M. , Langley Raymond J. 
Published: February 2018

AbstractImproved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups by using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance is validated in five cohorts of community-onset sepsis patients in which the models show summary AUROCs ranging from 0.765–0.89. Similar performance is observed in four cohorts of hospital-acquired sepsis. Combining the new gene-expression-based prognostic models with prior clinical severity scores leads to significant improvement in prediction of 30-day mortality as measured via AUROC and net reclassification improvement index These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis.
Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens
Authors: Hover Bradley M. , Kim Seong-Hwan , Katz Micah , Charlop-Powers Zachary , Owen Jeremy G. , Ternei Melinda A. , Maniko Jeffrey , Estrela Andreia B. , Molina Henrik , Park Steven , Perlin David S. , Brady Sean F. 
Published: February 2018

AbstractDespite the wide availability of antibiotics, infectious diseases remain a leading cause of death worldwide
1
. In the absence of new therapies, mortality rates due to untreatable infections are predicted to rise more than tenfold by 2050. Natural products (NPs) made by cultured bacteria have been a major source of clinically useful antibiotics. In spite of decades of productivity, the use of bacteria in the search for new antibiotics was largely abandoned due to high rediscovery rates2,3. As only a fraction of bacterial diversity is regularly cultivated in the laboratory and just a fraction of the chemistries encoded by cultured bacteria are detected in fermentation experiments, most bacterial NPs remain hidden in the global microbiome. In an effort to access these hidden NPs, we have developed a culture-independent NP discovery platform that involves sequencing, bioinformatic analysis and heterologous expression of biosynthetic gene clusters captured on DNA extracted from environmental samples. Here, we describe the application of this platform to the discovery of the malacidins, a distinctive class of antibiotics that are commonly encoded in soil microbiomes but have never been reported in culture-based NP discovery efforts. The malacidins are active against multidrug-resistant pathogens, sterilize methicillin-resistant Staphylococcus aureus skin infections in an animal wound model and did not select for resistance under our laboratory conditions.
Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells
Authors: Elgueta Claudio , Leroy Felix , Vielma Alex H. , Schmachtenberg Oliver , Palacios Adrian G. 
Published: February 2018

AbstractA17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.
Lateral Force Microscopy of Interfacial Nanobubbles: Friction Reduction and Novel Frictional Behavior
Authors: Yang Chih-Wen , Leung Kwan-tai , Ding Ren-Feng , Ko Hsien-Chen , Lu Yi-Hsien , Fang Chung-Kai , Hwang Ing-Shouh 
Published: February 2018

AbstractAtomic force microscopy is used to conduct single-asperity friction measurements at a water-graphite interface. Local mapping of the frictional force, which is based on the degree of the cantilever twisting, shows nearly friction-free when a tip scans over a nanobubble. Surprisingly, apart from being gapless, the associated friction loop exhibits a tilt in the cantilever twisting versus the tip’s lateral displacement with the slope depending on the loading force. The sign of the slope reverses at around zero loading force. In addition, the measured normal and lateral tip-sample interactions exhibit unison versus tip-sample separation. Theoretical analysis, based on the balance of forces on the tip originated from the capillary force of the nanobubble and the torsion of the cantilever, offers quantitative explanations for both the tilted friction loop and the unison of force curves. The analysis may well apply in a wider context to the lateral force characterization on cap-shaped fluid structures such as liquid droplets on a solid substrate. This study further points to a new direction for friction reduction between solids in a liquid medium.
In-situ visualization of sound-induced otolith motion using hard X-ray phase contrast imaging
Authors: Schulz-Mirbach Tanja , Olbinado Margie , Rack Alexander , Mittone Alberto , Bravin Alberto , Melzer Roland R. , Ladich Friedrich , Heß Martin 
Published: February 2018

AbstractRegarding the basics of ear structure-function relationships in fish, the actual motion of the solid otolith relative to the underlying sensory epithelium has rarely been investigated. Otolith motion has been characterized based on a few experimental studies and on approaches using mathematical modeling, which have yielded partially conflicting results. Those studies either predicted a simple back-and-forth motion of the otolith or a shape-dependent, more complex motion. Our study was designed to develop and test a new set-up to generate experimental data on fish otolith motion in-situ. Investigating the basic parameters of otolith motion requires an approach with high spatial and temporal resolution. We therefore used hard X-ray phase contrast imaging (XPCI). We compared two anatomically well-studied cichlid species, Steatocranus tinanti and Etroplus maculatus, which, among other features, differ in the 3D shape of their otoliths. In a water-filled tank, we presented a pure tone of 200 Hz to 1) isolated otoliths embedded in agarose serving as a simple model or 2) to a fish (otoliths in-situ). Our new set-up successfully visualized the motion of otoliths in-situ and therefore paves the way for future studies evaluating the principles of otolith motion.
Red blood cells are dynamic reservoirs of cytokines
Authors: Karsten Elisabeth , Breen Edmond , Herbert Benjamin R. 
Published: February 2018

AbstractRed blood cells (RBCs) have been shown to affect immune function and can induce inflammatory responses after transfusion. The transfusion of washed RBCs can significantly reduce adverse effects, however, the soluble factors that may mediate these effects have not been identified. Previous studies have identified, but not quantified, a small number of chemokines associated with RBCs. We isolated RBCs from healthy volunteers and quantified of a panel of 48 cytokines, chemokines, and growth factors in the lysate, cytosol, and conditioned media of these cells using Luminex®technology. This analysis revealed that, after correcting for white blood cell and platelet contamination, 46 cytokines were detected in RBC lysates, and the median concentration in RBCs was 12-fold higher than in the plasma. In addition, extensive washing of RBCs, such as that performed in proteomics analyses or prior to some RBC transfusions, significantly attenuated the release of six cytokines following incubation at 37 °C. This supports the hypothesis that, alongside its gas exchange function, RBCs play a role in cytokine signalling. This discovery may help supplement disease biomarker research and may shed light on adverse inflammatory processes that can follow RBC transfusion.
Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis
Authors: Wang Guoqi , Liu Hongyan , Wang Chengzhi , Ji Xiaojian , Gu Weijun , Mu Yiming 
Published: February 2018

AbstractTo assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched until March 2016. Trial sequential analysis (TSA) was conducted to control the risks of type I and II errors and calculate required information size (RIS). A total of 25 articles with 8481 participants were included. Compared with controls, cinacalcet administration did not reduce all-cause mortality (RR = 0.97, 95% CI = 0.89–1.05, P = 0.41, TSA-adjusted 95% CI = 0.86–1.08, RIS = 5260, n = 8386) or cardiovascular mortality (RR = 0.95, 95% CI = 0.83–1.07, P = 0.39, TSA-adjusted 95% CI = 0.70–1.26, RIS = 3780 n = 5418), but it reduced the incidence of parathyroidectomy (RR = 0.48, 95% CI = 0.40–0.50, P < 0.001, TSA-adjusted 95% CI = 0.39–0.60, RIS = 5787 n = 5488). Cinacalcet increased the risk of hypocalcemia (RR = 8.48, 95% CI = 6.37–11.29, P < 0.001, TSA-adjusted 95% CI = 5.25–13.70, RIS = 6522, n = 7785), nausea (RR = 2.12, 95% CI = 1.62–2.77, P < 0.001, TSA-adjusted 95% CI = 1.45–3.04, RIS = 4684, n = 7512), vomiting (RR = 2.00, 95% CI = 1.79–2.24, P < 0.001, TSA-adjusted 95% CI = 1.77–2.26, RIS = 1374, n = 7331) and diarrhea (RR = 1.17, 95% CI = 1.05–1.32, P = 0.006, TSA-adjusted 95% CI = 1.02–1.36, RIS = 8388, n = 6116). Cinacalcet did not significantly reduce the incidence of fractures (RR = 0.58, 95% CI = 0.21–1.59, P = 0.29, TSA-adjusted 95% CI = 0.01–35.11, RIS = 76376, n = 4053). Cinacalcet reduced the incidence of parathyroidectomy, however, it did not reduce all-cause and cardiovascular mortality, and increased the risk of adverse events including hypocalcemia and gastrointestinal disorders.
Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin
Authors: Vizoso-Vázquez Ángel , Lamas-Maceiras Mónica , González-Siso M. Isabel , Cerdán M. Esperanza 
Published: February 2018

AbstractIxr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic regulon and also controls the expression of other genes involved in the oxidative stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and modulates DNA repair. The influence of Ixr1 on transcription in the absence or presence of cisplatin has been analyzed in this work. Ixr1 regulates other transcriptional factors that respond to nutrient availability or extracellular and intracellular stress stimuli, some controlled by the TOR pathway and PKA signaling. Ixr1 controls transcription of ribosomal RNAs and genes encoding ribosomal proteins or involved in ribosome assembly. qPCR, ChIP, and 18S and 25S rRNAs measurement have confirmed this function. Ixr1 binds directly to several promoters of genes related to rRNA transcription and ribosome biogenesis. Cisplatin treatment mimics the effect of IXR1 deletion on rRNA and ribosomal gene transcription, and prevents Ixr1 binding to specific promoters related to these processes.
Stereochemical identification of glucans by oligothiophenes enables cellulose anatomical mapping in plant tissues
Authors: Choong Ferdinand X. , Bäck Marcus , Schulz Anette , Nilsson K. Peter. R. , Edlund Ulrica , Richter-Dahlfors Agneta 
Published: February 2018

AbstractEfficient use of plant-derived materials requires enabling technologies for non-disruptive composition analysis. The ability to identify and spatially locate polysaccharides in native plant tissues is difficult but essential. Here, we develop an optical method for cellulose identification using the structure-responsive, heptameric oligothiophene h-FTAA as molecular fluorophore. Spectrophotometric analysis of h-FTAA interacting with closely related glucans revealed an exceptional specificity for β-linked glucans. This optical, non-disruptive method for stereochemical differentiation of glycosidic linkages was next used for in situ composition analysis in plants. Multi-laser/multi-detector analysis developed herein revealed spatial localization of cellulose and structural cell wall features such as plasmodesmata and perforated sieve plates of the phloem. Simultaneous imaging of intrinsically fluorescent components revealed the spatial relationship between cell walls and other organelles, such as chloroplasts and lignified annular thickenings of the trachea, with precision at the sub-cellular scale. Our non-destructive method for cellulose identification lays the foundation for the emergence of anatomical maps of the chemical constituents in plant tissues. This rapid and versatile method will likely benefit the plant science research fields and may serve the biorefinery industry as reporter for feedstock optimization as well as in-line monitoring of cellulose reactions during standard operations.
Heparan sulfates facilitate harmless amyloidogenic fibril formation interacting with elastin-like peptides
Authors: Boraldi Federica , Moscarelli Pasquale , Bochicchio Brigida , Pepe Antonietta , Salvi Anna M. , Quaglino Daniela 
Published: February 2018

AbstractHeparan sulfates (HSs) modulate tissue elasticity in physiopathological conditions by interacting with various matrix constituents as tropoelastin and elastin-derived peptides. HSs bind also to protein moieties accelerating amyloid formation and influencing cytotoxic properties of insoluble fibrils. Interestingly, amyloidogenic polypeptides, despite their supposed pathogenic role, have been recently explored as promising bio-nanomaterials due to their unique and interesting properties. Therefore, we investigated the interactions of HSs, obtained from different sources and exhibiting various degree of sulfation, with synthetic amyloidogenic elastin-like peptides (ELPs), also looking at the effects of these interactions on cell viability and cell behavior using in vitro cultured fibroblasts, as a prototype of mesenchymal cells known to modulate the soft connective tissue environment. Results demonstrate, for the first time, that HSs, with differences depending on their sulfation pattern and chain length, interact with ELPs accelerating aggregation kinetics and amyloid-like fibril formation as well as self-association. Furthermore, these fibrils do not negatively affect fibroblasts’ cell growth and parameters of redox balance, and influence cellular adhesion properties. Data provide information for a better understanding of the interactions altering the elastic component in aging and in pathologic conditions and may pave the way for the development of composite matrix-based biomaterials.