bluuebunny/crossref_metadata_2025 huggingface dataset:
Eukaryotically expressed encapsulins as orthogonal compartments for multiscale molecular imaging
Authors: Sigmund Felix , Massner Christoph , Erdmann Philipp , Stelzl Anja , Rolbieski Hannes , Fuchs Helmut , de Angelis Martin Hrabé , Desai Mitul , Bricault Sarah , Jasanoff Alan , Ntziachristos Vasilis , Plitzko Jüergen , Westmeyer Gil G.
Published: November 2017

We have genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-controlled metal biomineralization. The orthogonal shell protein (EncA) from M. xanthus efficiently auto-assembled inside mammalian cells into nanocompartments to which sets of native (EncB,C,D) and engineered cargo proteins self-targeted. This enabled localized bimolecular fluorescence and enzyme complementation with selective access to substrates via the pores in the nanoshell. Encapsulation of the enzyme tyrosinase lead to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB or EncC) resulted in efficient iron sequestration that produced substantial contrast by magnetic resonance imaging (MRI) and enabled magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells also proved to be excellent genetically encoded markers for cryo-electron tomography (cryo-ET). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.
Integrating animal movement with habitat suitability for estimating dynamic landscape connectivity
Authors: van Toor Mariëlle L. , Kranstauber Bart , Newman Scott H. , Prosser Diann J. , Takekawa John Y. , Technitis Georgios , Weibel Robert , Wikelski Martin , Safi Kamran
Published: November 2017

Context

High-resolution animal movement data are becoming increasingly available, yet having a multitude of empirical trajectories alone does not allow us to easily predict animal movement. To answer ecological and evolutionary questions at a population level, quantitative estimates of a species’ potential to link patches or populations are of importance.

Objectives

We introduce an approach that combines movement-informed simulated trajectories with an environment-informed estimate of the trajectories’ plausibility to derive connectivity. Using the example of bar-headed geese we estimated migratory connectivity at a landscape level throughout the annual cycle in their native range.

Methods

We used tracking data of bar-headed geese to develop a multi-state movement model and to estimate temporally explicit habitat suitability within the species’ range. We simulated migratory movements between range fragments, and calculated a measure we called route viability. The results are compared to expectations derived from published literature.

Results

Simulated migrations matched empirical trajectories in key characteristics such as stopover duration. The viability of the simulated trajectories was similar to that of the empirical trajectories. We found that, overall, the migratory connectivity was higher within the breeding than in wintering areas, corresponding to previous findings for this species.

Conclusions

We show how empirical tracking data and environmental information can be fused for meaningful predictions of animal movements throughout the year and even outside the spatial range of the available data. Beyond predicting connectivity, our framework will prove useful for modelling ecological processes facilitated by animal movement, such as seed dispersal or disease ecology.
Modeling Dynamic Transcriptional Circuits with CRISPRi
Authors: Clamons Samuel , Murray Richard M.
Published: November 2017

Targeted transcriptional repression with catalytically inactive Cas9 (CRISPRi) promises to reproduce the functions of traditional synthetic transcriptional circuits, but with better orthogonality, programmability, and extensibility. However, CRISPRi lacks obvious cooperativity–a feature classically considered critical for several classic gene regulatory circuits. We use a simple dynamical model of CRISPRi to show that it can be used to build repressilators, toggle switches, and incoherent feed-forward loops. We also show that the function some of these circuits are expected to be sensitive to several key parameters, and we provide specifications for those parameters. Our modeling reveals key engineering requirements and considerations for the construction of dynamic CRISPRi circuits, and provides a roadmap for building those circuits.
High-throughput ANI Analysis of 90K Prokaryotic Genomes Reveals Clear Species Boundaries
Authors: Jain Chirag , Rodriguez-R Luis M. , Phillippy Adam M. , Konstantinidis Konstantinos T. , Aluru Srinivas
Published: November 2017

A fundamental question in microbiology is whether there is a continuum of genetic diversity among genomes or clear species boundaries prevail instead. Answering this question requires robust measurement of whole-genome relatedness among thousands of genomes and from diverge phylogenetic lineages. Whole-genome similarity metrics such as Average Nucleotide Identity (ANI) can provide the resolution needed for this task, overcoming several limitations of traditional techniques used for the same purposes. Although the number of genomes currently available may be adequate, the associated bioinformatics tools for analysis are lagging behind these developments and cannot scale to large datasets. Here, we present a new method, FastANI, to compute ANI using alignment-free approximate sequence mapping. Our analyses demonstrate that FastANI produces an accurate ANI estimate and is up to three orders of magnitude faster when compared to an alignment (e.g., BLAST)-based approach. We leverage FastANI to compute pairwise ANI values among all prokaryotic genomes available in the NCBI database. Our results reveal a clear genetic discontinuity among the database genomes, with 99.8% of the total 8 billion genome pairs analyzed showing either >95% intra-species ANI or <83% inter-species ANI values. We further show that this discontinuity is recovered with or without the most frequently represented species in the database and is robust to historic additions in the public genome databases. Therefore, 95% ANI represents an accurate threshold for demarcating almost all currently named prokaryotic species, and wide species boundaries may exist for prokaryotes.
Molecule guided laser ablation as a novel therapeutic strategy to control itch
Authors: Nocchi Linda , D’Attilia Mariangela , Roy Nainika , Dhandapani Rahul , Traista Andrei , Maffei Mariano , Castaldi Laura , Perlas Emerald , Heppenstall Paul A.
Published: November 2017

Itch is a major symptom of many chronic skin diseases that can exacerbate inflammation by provoking excessive scratching and causing skin damage. Here we develop a novel technology to control itch through molecular guided delivery of a phototoxic agent and near infrared (IR) illumination of the skin. Exploiting the selective binding of the pruritogen Interleukin-31 to itch sensing cells, we generate an engineered IL31SNAPligand derivative (IL31K138A-SNAP) that binds to cells but does not evoke signaling or provoke scratching when injected in vivo. Conjugation of IL31K138A-SNAPto the photosensitizer IRDye®700DX phthalocyanine (IR700) and injection of the skin results in long-term reversal of scratching behavior evoked by IL31 upon near IR illumination. We further develop a topical preparation of IL31K138A-SNAP-IR700 that strikingly, reverses behavioral and dermatological indicators in mouse models of Atopic Dermatitis (AD) and the genetic skin disease Familial Primary Localized Cutaneous Amyloidosis (FPLCA). We demonstrate that this therapeutic effect results from selective retraction of itch sensing neurons in the skin, breaking the cycle of itch and disruption of the skin’s barrier function. Thus, molecule guided photoablation is a powerful new technology for controlling itch and treating inflammatory skin diseases.
A design framework and exemplar metrics for FAIRness
Authors: Wilkinson Mark D. , Sansone Susanna-Assunta , Schultes Erik , Doorn Peter , Bonino da Silva Santos Luiz Olavo , Dumontier Michel
Published: November 2017

“FAIRness” - the degree to which a digital resource is Findable, Accessible, Interoperable, and Reusable - is aspirational, yet the means of reaching it may be defined by increased adherence to measurable indicators. We report on the production of a core set of semi-quantitative metrics having universal applicability for the evaluation of FAIRness, and a rubric within which additional metrics can be generated by the community. This effort is the output from a stakeholder-representative group, founded by a core of FAIR principles’ co-authors and drivers. We now seek input from the community to more broadly discuss their merit.
GABAergic deficits and schizophrenia-like behaviors in a mouse model carrying patient-derived neuroligin-2 R215H mutation
Authors: Jiang Dong-Yun , Wu Zheng , Hu Yi , Yee Siu-Pok , Chen Gong
Published: November 2017

Schizophrenia (SCZ) is a severe mental disorder characterized by delusion, hallucination, and cognitive deficits. We have previously identified from schizophrenia patients a loss-of-function mutation Arg215 → His215 (R215H) of neuroligin 2 (NLGN2) gene, which encodes a cell adhesion molecule critical for GABAergic synapse formation and function. Here, we generated a novel transgenic mouse line with neuroligin-2 (NL2) R215H mutation, which showed a significant loss of NL2 protein, reduced GABAergic transmission, and impaired hippocampal activation. Importantly, R215H KI mice displayed anxiety-like behaviors, impaired pre-pulse inhibition (PPI), cognition deficits and abnormal stress responses, recapitulating several key aspects of schizophrenia-like behavior. Our results demonstrate a significant impact of a single point mutation NL2 R215H on brain functions, providing a novel animal model for the study of schizophrenia and neuropsychiatric disorders.
Energy saving in vision at the first synapse: The ON and OFF pathways measure temporal differences
Authors: ter Haar Romeny Bart M.
Published: November 2017

The inner plexiform layer (IPL) of mammalian retina has a precise bisublaminar organization in an inner on- and an outer off-layer, innervated by spatially segregated on- and off-cone bipolar cell inputs. Also, the processes of starburst amacrine cells are segregated into on and off sublaminae of the IPL. Distances between overlapping on-off pair retinal ganglion cell dendritic tree centers are markedly smaller than between on-on or off-off centers, indicating simultaneously sampling the same space. Despite dekades of research, no good model exists for the role of the on- and off pathways. Here I propose that the on- and off pairs are temporally subtracted, with one channel delayed in time, likely in a higher cortical center. The on- and off receptive fields give at every retinal location an I+ and I-signal, where I is intensity, velocity, color. Subsequent frame subtraction is a basis function of every surveillance camera for vision, and in MPEG video/sound compression. The model explains the many phenomena observed when the retinal image is stabilized. The separation of layers in the LGN fits with the notion of a time delay at higher cortical level. The directionalty observed in micro-saccades is typically perpendicular to the main edges in the scene. Precise measurement of spatio-temporal receptive field kernels shows that time is processed in the visual system as a real-time process, i.e. with a logarithmic time axis. As only contours and textures are transmitted, it is a very effective design strategy of the visual system to conserve energy, in a brain that typically uses 25 Watt and very low neuron firing frequencies. The higher visual centers perform the fill-in (inpainting) with such efficiency, that the subtraction always goes unnoticed.
ProLego: tool for extracting and visualizing topological modules in protein structures
Authors: Khan Taushif , Panday Shailesh Kumar , Ghosh Indira
Published: November 2017

Background

In protein design, correct use of topology is among the initial and most critical feature. Meticulous selection of backbone topology aids in drastically reducing the structure search space. With ProLego, we present a server application to explore the component aspect of protein structures and provide an intuitive and efficient way to scan the protein topology space.

Result

We have implemented in-house developed “topological representation” in an automated-pipeline to extract protein topology from given protein structure. Using the topology string, ProLego, compares topology against a non-redundant extensive topology database (ProLegoDB) as well as extracts constituent topological modules. The platform offers interactive topology visualization graphs.

Conclusion

ProLego, provides an alternative but comprehensive way to scan and visualize protein topology along with an extensive database of protein topology.

ProLego can be found at http://www.proteinlego.com
FamPlex: a resource for entity recognition and relationship resolution of human protein families and complexes in biomedical text mining
Authors: Bachman John A , Gyori Benjamin M , Sorger Peter K
Published: November 2017

Background

For automated reading of scientific publications to extract useful information about molecular mechanisms it is critical that genes, proteins and other entities be correctly associated with uniform identifiers, a process known as named entity linking or “grounding.” Correct grounding is essential for resolving relationships among mined information, curated interaction databases, and biological datasets. The accuracy of this process is largely dependent on the availability of machine-readable resources associating synonyms and abbreviations commonly found in biomedical literature with uniform identifiers.

Results

In a task involving automated reading of ∼215,000 articles using the REACH event extraction software we found that grounding was disproportionately inaccurate for multi-protein families (e.g., “AKT”) and complexes with multiple subunits (e.g.”NF-κB”). To address this problem we constructed FamPlex, a manually curated resource defining protein families and complexes as they are commonly encountered in biomedical text. In FamPlex the gene-level constituents of families and complexes are defined in a flexible format allowing for multi-level, hierarchical membership. To create FamPlex, text strings corresponding to entities were identified empirically from literature and linked manually to uniform identifiers; these identifiers were also mapped to equivalent entries in multiple related databases. FamPlex also includes curated prefix and suffix patterns that improve named entity recognition and event extraction. Evaluation of REACH extractions on a test corpus of ∼54,000 articles showed that FamPlex significantly increased grounding accuracy for families and complexes (from 15% to 71%). The hierarchical organization of entities in FamPlex also made it possible to integrate otherwise unconnected mechanistic information across families, subfamilies, and individual proteins. Applications of FamPlex to the TRIPS/DRUM reading system and the Biocreative VI Bioentity Normalization Task dataset demonstrated the utility of FamPlex in other settings.

Conclusion

FamPlex is an effective resource for improving named entity recognition, grounding, and relationship resolution in automated reading of biomedical text. The content in FamPlex is available in both tabular and Open Biomedical Ontology formats at https://github.com/sorgerlab/famplex under the Creative Commons CC0 license and has been integrated into the TRIPS/DRUM and REACH reading systems.
Origin, evolution, and distribution of the molecular machinery for biosynthesis of sialylated lipooligosaccharide structures in Campylobacter coli
Authors: Culebro Alejandra , Machado Miguel P. , Carriço João André , Rossi Mirko
Published: November 2017

Campylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common bacterial etiological agent in the autoimmune Guillain-Barré syndrome (GBS). Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of the disease. LOS-associated genes involved in the synthesis (neuABC) and transfer of sialic acid (sialyltranferases) are essential in C. jejuni to synthesize ganglioside-like LOS. Therefore these genes have been identified as GBS markers. So far, scarce genetic evidence supports C. coli as a GBS causative agent despite being isolated from GBS patients. Here we show that genes putatively involved in sialic acid transfer are widely distributed in the C. coli population. Evidence found herein suggests that a small group of C. coli strains are very likely to express ganglioside mimics, implying that C. coli can potentially trigger GBS. C. coli also presents a larger repertoire of sialyltransferases than C. jejuni and loss of functions of some those LOS-associated genes has happened during adaptation to agriculture niche. Nevertheless, the activity of these sialyltransferases and their role in shaping C. coli population is yet to be explored.
The structure of SALM5 suggests a dimeric assembly for the presynaptic RPTP ligand recognition
Authors: Karki Sudeep , Paudel Prodeep , Sele Celeste , Shkumatov Alexander V. , Kajander Tommi
Published: November 2017

Synaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently several families of leucine rich repeat domain containing neuronal adhesion molecules have been characterized, including netrin G-ligands, LRRTMs, and the SALM family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia. The SALM family proteins SALM3 and SALM5, similar to SLITRKs, have been shown to bind to the presynaptic receptor protein tyrosine phosphatase (RPTP) family ligands. Here we present the 3 Å crystal structure of the SALM5 LRR-Ig domain construct, and biophysical studies that verify the crystallographic results. We show that both SALM3 and SALM5 extracellular domains form similar dimeric structures, in which the LRR domains form the dimer interface. Both proteins bind to the RPTP lg-domains with micromolar affinity. SALM3 shows a clear preference for RPTP-ligands with the meB splice insert. This is in accordance with previous results showing that the LRR domain is also required for the ligand binding. Our structural studies and sequence conservation analysis suggests a ligand binding site and mechanism for RPTP binding via the dimeric LRR domain region.
Early Archean origin of heterodimeric Photosystem I
Authors: Cardona Tanai
Published: November 2017

When and how oxygenic photosynthesis originated remains controversial. Wide uncertainties exist for the earliest detection of biogenic oxygen in the geochemical record or the origin of water oxidation in ancestral lineages of the phylum Cyanobacteria. A unique trait of oxygenic photosynthesis is that the process uses a Type I reaction centre with a heterodimeric core, also known as Photosystem I, made of two distinct but homologous subunits, PsaA and PsaB. In contrast, all other known Type I reaction centres in anoxygenic phototrophs have a homodimeric core. A compelling hypothesis for the evolution of a heterodimeric Type I reaction centre is that the gene duplication that allowed the divergence of PsaA and PsaB was an adaptation to incorporate photoprotective mechanisms against the formation of reactive oxygen species, therefore occurring after the origin of water oxidation to oxygen. Here I show, using sequence comparisons and Bayesian relaxed molecular clocks that this gene duplication event may have occurred in the early Archean more than 3.4 billion years ago, long before the most recent common ancestor of crown group Cyanobacteria and the Great Oxidation Event. If the origin of water oxidation predated this gene duplication event, then that would place primordial forms of oxygenic photosynthesis at a very early stage in the evolutionary history of life.
Crystal structure and Hirshfeld surface analysis of hexakis(μ-benzoato-κ2O:O′)bis(pyridine-3-carbonitrile-κN1)trizinc(II)
Authors: Hökelek Tuncer , Özbek Elif , Sertçelik Mustafa , Şahin Yenice Çiğdem , Necefoğlu Hacali
Published: November 2017

The asymmetric unit of the title complex, [Zn3(C7H5O2)6(C6H4N2)2], contains one half of the complex molecule,i.e.one and a half ZnIIcations, three benzoate (Bnz) and one pyridine-3-carbonitrile (Cpy) molecule; the Bnz anions act as bidentate ligands through the carboxylate O atoms, while the Cpy ligand acts as a monodentate N(pyridine)-bonding ligand. The complete centrosymmetric trinuclear complex thus comprises a linear array of three ZnIIcations. The central ZnIIcation shows an octahedral coordination and is bridged to each of the terminal ZnIIcations by three Bnz anions. By additional coordination of the CPy ligand, the terminal ZnIIcations adopt a trigonal–pyramidal coordination environment. In the crystal, the Bnz anions link to the Cpy N atomsviaweak C—H...N hydrogen bonds, forming a two-dimensional network. C—H...π and π–π interactions [between the benzene and pyridine rings of adjacent molecules with an intercentroid distance of 3.850 (4) Å] help to consolidate a three-dimensional architecture. The Hirshfeld surface analysis confirms the role of H-atom contacts in establishing the packing.
N′-[(1Z)-1-(3-Methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-ylidene)ethyl]-2-[(4-methylphenyl)sulfanyl]acetohydrazide
Authors: Mohamed Shaaban K. , Mague Joel T. , Akkurt Mehmet , Abbady Mohamed S. , Bakhite Etify A. , Albayati Mustafa R.
Published: November 2017

In the title compound, C21H22N4O2S, the dihedral angle between the pyrazole ring and adjacent benzene ring is 6.4 (1)°. The molecular conformation is influenced by intramolecular N—H...O and C—H...O hydrogen bonds. In the crystal, N—H...O hydrogen bonds plus C—H...π and π–π stacking interactions form chains extending in thea-axis direction. The chains are linked by complementary pairs of C—H...π interactions.
Family‐based interventions for children and adolescents with functional somatic symptoms: a systematic review
Authors: Hulgaard Ditte , Dehlholm‐Lambertsen Gitte , Rask Charlotte Ulrikka
Published: November 2017

Functional somatic symptoms (FSS), defined as physical symptoms that cannot be fully explained by organic pathology, are prevalent in youngsters worldwide. When severe, they can pose a major burden on the affected individual as well as on society. FSS seem to aggregate in families, and family variables may play a key role in symptom development and perpetuation. It may, therefore, be important to work with the family when managing FSS.

The aim of this systematic review was to explore and describe family‐based interventions used for children and adolescents with FSS, further to evaluate the overall quality of the research in this area. Sixteen studies were included. The psychological orientation for the applied treatment was based on systemic or cognitive behavioural therapy. Treatment focused on family illness beliefs and on a shift away from somatic symptom attribution to alternative explanations that were shaped by the psychological orientation of the applied treatment.

Practitioner points

Family influences are significant for functional somatic symptoms in youngsters

Family intervention may be a relevant treatment approach for youngsters with functional somatic symptoms

Family‐based psychotherapy for youngsters with functional somatic symptoms is mainly based on cognitive behavioural therapy or on systemic family therapy

Illness beliefs of the child/adolescent as well as illness beliefs of the family as a whole could be important treatment targets in young people with functional somatic symptoms
Analysis of differential proteins in two different wing‐types of female Nilaparvata lugens
Authors: Liang An‐Wen , Liu Ting‐Ting , Liang Zi‐Qiang , Wang Fang‐Hai
Published: November 2017

Nilaparvata lugens (stal) is a rice pest and contains long‐winged and short‐winged varieties, called the wing differentiation. This study compared the protein profiles of the two wing‐types in females and two wing‐disc types 5th‐instar females by two‐dimensional electrophoresis analysis. We detected 172 and 174 protein spots in adults and 5th‐instar nymphs, respectively. The number of proteins with higher content in the long‐winged (disc) individuals is much more than that in the short‐winged (disc) individuals. A total of 32 differential protein spots were found, of which 20 were successfully identified. Their main function is about catabolic process, fiber and nucleoside binding, and they constitute 52 protein–protein interactions, which is around the glycolysis as the core. These results enrich the research on the protein Level in wing development, and provide more references for future studies.
Precise Quantitative Assessment of the Clinical Performances of Two High‐Flux Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood‐Based Simple Kinetic Model Versus Direct Dialysis Quantification
Authors: Lim Paik‐Seong , Lin Yuyu , Chen Minfeng , Xu Xiaoqi , Shi Yun , Bowry Sudhir , Canaud Bernard
Published: November 2017

Highly permeable dialysis membranes with better design filters have contributed to improved solute removal and dialysis efficacy. However, solute membrane permeability needs to be well controlled to avoid increased loss of albumin that is considered to be detrimental for dialysis patients. A novel high‐flux dialyzer type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone membrane modified with nano‐controlled spinning technology to enhance the elimination of a broader spectrum of uremic toxins has been released. The aim of this study was to compare in the clinical setting two dialyzer types having the same surface area, the current (FX dialyzer) and the new dialyzer generation (FX CorDiax), with respect to solute removal capacity over a broad spectrum of markers, including assessment of albumin loss based on a direct dialysis quantification method. We performed a crossover study following an A1‐B‐A2 design involving 10 patients. Phase A1 was 1 week of thrice‐weekly bicarbonate hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with a similar treatment regimen but with a new FX CorDiax dialyzer and finally the phase A2 was repeated with FX dialyzer as the former phase. Solute removal markers of interest were assessed from blood samples taken before and after treatment and from total spent dialysate collection (direct dialysis quantification) permitting a mass transfer calculation (mg/session into total spent dialysate/ultrafiltrate). On the blood side, there were no significant differences in the solute percent reduction between FX CorDiax 80 and FX 80. On the dialysate side, no difference was observed regarding eliminated mass of different solutes including β2‐microglobulin (143.1 ± 33.6 vs. 138.3 ± 41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 ± 0.51 vs. 2.14 ± 0.75 g, P = 0.04), and albumin (0.41 ± 0.21 vs. 1.22 ± 0.51 g, P < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80 dialyzer. The results of this cross‐over study indicate that the new FX CorDiax dialyzer has highly effective removal of middle molecules, without any concomitant increase in total protein and albumin loss. The clinical relevance and potential benefit of this finding needs to be determined.
Sofosbuvir and velpatasvir with or without voxilaprevir in direct‐acting antiviral‐naïve chronic hepatitis C: patient‐reported outcomes from POLARIS 2 and 3
Authors: Younossi Z. M. , Stepanova M. , Jacobson I. M. , Asselah T. , Gane E. J. , Lawitz E. , Foster G. R. , Roberts S. K. , Thompson A. J. , Willems B. E. , Welzel T. M. , Pearlman B. , Younossi I. , Racila A. , Henry L.
Published: November 2017

Background

Chronic hepatitis C infection leads to impairment of patient‐reported outcomes (PROs). Treatment with direct‐acting antiviral regimens results in short‐ and long‐term improvement of these outcomes.

Aim

To assess PROs in patients treated with a newly developed direct‐acting antiviral, a fixed‐dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX).

Methods

The PRO data were collected from participants of POLARIS‐2 and POLARIS‐3 clinical trials (DAA‐naïve, all HCV genotypes). Participants self‐administered SF‐36v2, FACIT‐F, CLDQ‐HCV and WPAI:SHP instruments at baseline, during treatment, and in follow‐up.

Results

Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment‐naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%‐98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0‐100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post‐treatment week 12, +3.9 to +20.1 by post‐treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05).

Conclusions

The pan‐genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients’ experience both during treatment and after achieving sustained virologic response in DAA‐naïve patients with HCV.
Tumor invasion to the arteries feeding the gallbladder as a novel risk factor for cholecystitis after metallic stent placement in distal malignant biliary obstruction
Authors: Sogabe Yuko , Kodama Yuzo , Honjo Hajime , Aoyama Ikuo , Muramoto Yuya , Koga Eri , Yanaidani Takafumi , Kawai Munenori , Yoshikawa Teppei , Matsumoto Shimpei , Matsumoto Astushi , Mori Yoshiharu , Ono Chikage , Nishida Miyu , Nishida Yoshihiro , Mikami Takao , Matsunaga Yasuhiro , Miyamoto Yukiko , Kitami Motoya , Nishikawa Koji , Kondo Masahiko , Miyake Naoki , Kawanami Chiharu , Seno Hiroshi
Published: November 2017

Background and Aim

Cholecystitis is a major complication after self‐expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement.

Methods

Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016.

Results

Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow‐up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57–137.18; P = 0.001) and 25.26 (95% CI, 4.12–154.98; P < 0.001), respectively.

Conclusions

This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.
Pediatric acute kidney injury induced by concomitant vancomycin and piperacillin–tazobactam
Authors: Abouelkheir Manal , Alsubaie Sarah
Published: November 2017

Background

Vancomycin is very commonly used in combination with piperacillin–tazobactam (PTZ) as the initial empiric treatment for moderate–severe infection, whenever coverage for both methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in adults has recently been reported to significantly increase the risk of acute kidney injury (AKI) relative to vancomycin monotherapy; such reports in pediatrics, however, are sparse.

Methods

A retrospective chart review was conducted of pediatric patients, aged 0–14 years, who were admitted to the general wards or intensive care unit and developed AKI after receiving vancomycin and PTZ concomitantly for >48 h. AKI is defined as a decrease in estimated glomerular filtration rate ≥50% from baseline. Cases were identified by reviewing the Adverse Drug Reaction program database at King Saud University Medical City in Saudi Arabia from January 2015 to June 2016.

Results

Eight children admitted to the present hospital and who received concomitant vancomycin and PTZ treatment for pneumonia (n = 7) or febrile neutropenia (n = 1) developed drug‐induced nephrotoxicity. Drug Interaction Probability Scale (DIPS) score for causation assessment was 9 in all cases (highly probable).

Conclusion

Caution in utilizing the combination of vancomycin and PTZ is warranted in pediatric patients. Health‐care professionals should be vigilant if this combination is to be initiated, and ensure close monitoring of renal function. Antibiotic therapy de‐escalation should be considered as soon as culture results are available.
‘Last In–First Out’: seasonal variations of non‐structural carbohydrates, glucose‐6‐phosphate and ATP in tubers of two Arum species
Authors: Petrussa E. , Boscutti F. , Vianello A. , Casolo V.
Published: November 2017

Knowledge on the metabolism of polysaccharide reserves in wild species is still scarce. In natural sites we collected tubers of Arum italicum Mill. and A. maculatum L. – two geophytes with different apparent phenological timing, ecology and chorology – during five stages of the annual cycle in order to understand patterns of reserve accumulation and degradation.

Both the entire tuber and its proximal and distal to shoot portion were utilised. Pools of non‐structural carbohydrates (glucose, sucrose and starch), glucose‐6‐phosphate and ATP were analysed as important markers of carbohydrate metabolism.

In both species, starch and glucose content of the whole tuber significantly increased from sprouting to the maturation/senescence stages, whereas sucrose showed an opposite trend; ATP and glucose‐6‐phosphate were almost stable and dropped only at the end of the annual cycle. Considering the two different portions of the tuber, both ATP and glucose‐6‐phosphate concentrations were higher in proximity to the shoot in all seasonal stages, except the flowering stage.

Our findings suggest that seasonal carbon partitioning in the underground organ is driven by phenology and occurs independently of seasonal climate conditions. Moreover, our results show that starch degradation, sustained by elevated ATP and glucose‐6‐phosphate pools, starts in the peripheral, proximal‐to‐shoot portion of the tuber, consuming starch accumulated in the previous season, as a ‘Last In–First Out’ mechanism of carbohydrate storage.
Outcome of 9 dogs treated with stereotactic radiation therapy for primary or metastatic vertebral osteosarcoma
Authors: Swift K. E. , LaRue S. M.
Published: November 2017

Primary and metastatic vertebral osteosarcoma (OSA) in the dog carries an overall guarded prognosis. Previously reported definitive treatments in dogs with vertebral OSA have included surgery, radiotherapy, chemotherapy or a combination of those therapies. This retrospective study was completed to determine patterns of failure, duration of local control and survival time in dogs with vertebral OSA treated with stereotactic radiation therapy (SRT). Nine dogs were treated with SRT for vertebral OSA. Protocols ranged from 1 to 5 fractions with total prescription ranging from 13.5 to 36 Gy. Six dogs had primary lesions and 3 had metastatic lesions. Neurologic score improved in 4 patients, remained the same in 4 and worsened in 1. Five of the 6 dogs that presented with assessable spinal pain had reported improvement in pain. Overall median survival time was 139 days and median duration of pain control was 77 days. There was not a statistically significant survival difference between dogs presenting with primary or metastatic disease, or dogs that had improvement in neurologic score following SRT. The data suggests similar survival times to the previously reported definitive treatments in dogs with vertebral OSA and displays continued difficulty in controlling this tumour. The dose limiting structure is the late responding spinal cord, but many of the patients herein died prior to the expected time to development of late radiation side effects.
Salmonella in breeding pigs: Shedding pattern, transmission of infection and the role of environmental contamination in Irish commercial farrow‐to‐finish herds
Authors: Lynch H. , Walia K. , Leonard F. C. , Lawlor P. G. , Manzanilla E. G. , Grant J. , Duffy G. , Gardiner G. E. , Cormican M. , King J. , Markey B. K. , Fanning S. , Argüello H.
Published: November 2017

This study aimed to provide new insights into the epidemiology of Salmonella in pig production, focusing on potential shedding patterns in breeding pigs throughout a full production cycle and the risk of transmission of infection from the sow to her offspring. A longitudinal study was conducted on five farrow‐to‐finish commercial pig farms. In each herd, shedding of Salmonella in faeces was monitored in breeders through service, gestation and lactation. Swabs of the farrowing room floor and pools of faeces from piglets were collected on two occasions during lactation. Environmental pen swabs were also taken in the weaning and finisher houses. Salmonella isolates were serotyped, tested for antimicrobial resistance (AMR) and typed by Multiple‐Locus Variable number tandem repeat Analysis (MLVA). Shedding by breeding pigs was low in all stages of the production cycle; 5% of sows shed at service, the production stage with highest risk of shedding (p < .01), 1.6% shed during gestation and 2.5% after farrowing. Salmonella was detected in 4% of piglet faecal pools in the second week post‐farrowing and 5% in the fourth week. Serotyping and AMR profiles of Salmonella isolates revealed that strains in sows and gilts were mostly different from strains isolated in weaner and finisher facilities. MLVA typing confirmed that the source of infection in piglets was in most instances the contaminated environment rather than their dam. Based on the typing results, it appears that sows do not pose a major risk in the maintenance and transmission of Salmonella to their progeny but instead the contaminated pen environment is more significant in the perpetuation of the organism on farm.
Identification of Static Loading Conditions Using Piezoelectric Sensor Arrays
Authors: Zhang He , Shen Mingzhou , Zhang Yangyang , Chen Yisheng , Lü Chaofeng
Published: November 2017

To make sure the safety, durability, and serviceability of structures in-service, health monitoring systems (HMS) are widely used in management of civil infrastructures in recent years. Compared with traditional force sensors, lead zirconium titanate (PZT) sensor performs better in smart sensing in HMS with advantages of high sensitivity, self-powering and fast response to highly dynamic load. Here, we propose to utilize PZT sensor arrays to identify the position and magnitude of external loads that are applied on a simply supported beam. An identification method is proposed based on experimental tests and theoretical electromechanical analyses, which is proved effective by comparing the identified parameters with the actually applied loading conditions and signals recorded by commercial force sensors. Experimental observations also reveal that PZT sensors respond faster to loading process than commercial force sensor, which makes it qualified in identification of transient loading such as impact processing in loading history. Results also demonstrate the applicability of the method to identify multiple concentrated load and the average moving speed of the applied load. The current method may provide a useful tool for identifying load conditions on various beam structures.
Three-dimensional photolithography using built-in lens mask
Authors: Tanaka Toshiki , Sugihara Daiki , Sasago Masaru , Kikuta Hisao , Kawata Hiroaki , Hirai Yoshihiko
Published: November 2017

Three-dimensional lithography processes are required to fabricate the complex structures of advanced MEMS devices. The built-in lens mask has a complex transmittance amplitude and emulates the optical wave planes of arbitrarily shaped images that are to be focused on a focal plane. In our previous work, the authors proposed a novel three-dimensional imaging method using a multifocusing built-in lens mask in a computational simulation study. In this work, the authors study the three-dimensional photolithography process experimentally using this built-in lens mask. A pyramidal frame pattern is used to expose a negative thick resist layer (SU-8), and three-dimensional structures are successfully obtained using a single mask and a single-shot photolithography process. The experimental results agree fairly well with those from the computational simulations.
Sound production patterns of big-clawed snapping shrimp (Alpheus spp.) are influenced by time-of-day and social context
Authors: Lillis Ashlee , Perelman Jessica N. , Panyi Apryle , Aran Mooney T.
Published: November 2017

Snapping shrimp are perhaps the most pervasive sources of biological sound in the ocean. The snapping sounds of cryptic shrimp colonies in shallow coastal habitats worldwide create a near-continuous crackling with high spatiotemporal variability, yet the underlying acoustic ecology is not well understood. This study investigated sound production rates and acoustic behavior of snapping shrimp species common in the Western Atlantic Ocean and Gulf of Mexico (Alpheus heterochaelis and Alpheus angulosus). Snap rates were measured in a controlled laboratory setting under natural light, temperature, and substrate conditions for shrimp held individually, in pairs, and in a ten-shrimp mesocosm, to test hypotheses that acoustic activity varies with time-of-day and social context. Spontaneous snapping was observed for 81 out of 84 solitary shrimp monitored. Time-of-day influenced snap output for individuals and same-sex pairs—higher rates occurred during dusk and night, compared to daylight hours, but this pattern was inconsistent for opposite-sex pairs and a mixed-sex group. These laboratory results provide insight into behavioral rhythms that may influence snapping patterns in natural populations, and underscore the limited understanding of a major sound source in marine environments.
Career Development and Learning Pathways of Paralympic Coaches With a Disability
Authors: Douglas Scott , Falcão William R. , Bloom Gordon A.
Published: November 2017

The purpose of this study was to gain an understanding of the career development and learning pathways of Paralympic head coaches who previously competed as Paralympic athletes. Each coach participated in a semistructured interview. A thematic analysis of the data revealed three higher order themes, which were called becoming a coach, learning to coach, and lifelong learning and teaching. Across these themes, participants discussed interactions with other coaches and athletes with a disability, learning from mentors and coaching clinics, as well as limited formal educational opportunities they experienced transitioning from athlete to head coach. The findings revealed that they acquired most of their knowledge from a combination of knowledge gained as athletes and informal sources, including trial and error. They also stressed the need for enhanced recruiting of parasport coaches and parasport coach education opportunities that would enhance programs for athletes with physical disabilities, from grassroots to Paralympic levels.
Interdisciplinarity and Adapted Physical Activity
Authors: Szostak Rick
Published: November 2017

The purpose of the paper was to draw lessons for the field of adapted physical activity from the interrelated literatures on interdisciplinarity, creativity, and team research. In each of these literatures, strategies have been identified that have been found to be useful by previous researchers. Lack of familiarity with these strategies can result in unsuccessful research projects or in the devotion of scarce resources to the reinvention of such strategies. The first section in the paper in particular addresses questions that arose at the 2016 North American Federation of Adapted Physical Activity symposium in Edmonton, Alberta.
Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance
Authors: Hector Amy J. , Phillips Stuart M.
Published: November 2017

There exists a large body of scientific evidence to support protein intakes in excess of the recommended dietary allowance (RDA) (0.8 g protein/kg/day) to promote the retention of skeletal muscle and loss of adipose tissue during dietary energy restriction. Diet-induced weight loss with as low as possible ratio of skeletal muscle to fat mass loss is a situation we refer to as high-quality weight loss. We propose that high-quality weight loss is often of importance to elite athletes in order to maintain their muscle (engine) and shed unwanted fat mass, potentially improving athletic performance. Current recommendations for protein intakes during weight loss in athletes are set at 1.6–2.4 g protein/kg/day. However, the severity of the caloric deficit and type and intensity of training performed by the athlete will influence at what end of this range athletes choose to be. Other considerations regarding protein intake that may help elite athletes achieve weight loss goals include the quality of protein consumed, and the timing and distribution of protein intake throughout the day. This review highlights the scientific evidence used to support protein recommendations for high-quality weight loss and preservation of performance in athletes. Additionally, the current knowledge surrounding the use of protein supplements, branched chain amino acids (BCAA), β-hydroxy β-methylbutyrate (HMB), and other dietary supplements with weight loss claims will be discussed.
Self-Talk in a SCUBA Diving Context
Authors: Van Raalte Judy L. , Wilson Lorraine , Cornelius Allen , Brewer Britton W.
Published: November 2017

Theory suggests that matching self-talk to sport demands can result in performance benefits, but the effects of self-talk in adventure-sport contexts that feature high risk (e.g., self-contained underwater breathing apparatus [SCUBA] diving) have not been studied. This research explored the effects of instructional and motivational self-talk in a high-risk adventure-sport context. Students (N = 78) enrolled in SCUBA diving courses were randomly assigned to self-talk (instructional, motivational) or control conditions; practiced self-talk and SCUBA diving skills; rated their levels of effort, confidence, and focus; and were evaluated during certification dives. Results indicated that participants gained confidence over time. The instructional-self-talk group reported being significantly more focused and confident during certification dives than the motivational-self-talk group. These results demonstrate the efficacy of matching self-talk to task demands in the high-risk context of adventure sports.