bluuebunny/crossref_metadata_2025 huggingface dataset:
REDUCING POTENTIALLY INAPPROPRIATE PRESCRIBING FOR OLDER PEOPLE IN PRIMARY CARE: COST-EFFECTIVENESS OF THE OPTI-SCRIPT INTERVENTION
Authors: Gillespie Paddy , Clyne Barbara , Raymakers Adam , Fahey Tom , Hughes Carmel M. , Smith Susan M.
Published: October 2017

Objectives: This study examines the cost-effectiveness of the OPTI-SCRIPT intervention on potentially inappropriate prescribing in primary care.

Methods: Economic evaluation, using incremental cost-effectiveness and cost utility analyses, conducted alongside a cluster randomized controlled trial of twenty-one general practices and 196 patients, to compare a multifaceted intervention with usual practice in primary care in Ireland. Potentially inappropriate prescriptions (PIPs) were determined by a pharmacist. Incremental costs, PIPs, and quality-adjusted life-years (QALYs) at 12-month follow-up were estimated using multilevel regression. Uncertainty was explored using cost-effectiveness acceptability curves.

Results: The intervention was associated with a nonsignificant mean cost increase of €407 (95 percent CIs, −357–1170), a significant mean reduction in PIPs of 0.379 (95 percent CI, 0.092–0.666), and a nonsignificant mean increase in QALYs of 0.013 (95 percent CIs, −0.016–0.042). The incremental cost per PIP avoided was €1,269 (95 percent CI, −1400–6302) and the incremental cost per QALY gained was €30,535 (95 percent CI, −334,846–289,498). The probability of the intervention being cost-effective was 0.602 at a threshold value of €45,000 per QALY gained and was at least 0.845 at threshold values of €2,500 per PIP avoided and higher.

Conclusions: While the OPTI-SCRIPT intervention was effective in reducing potentially inappropriate prescribing in primary care in Ireland, our findings highlight the uncertainty with respect to its cost-effectiveness. Further studies are required to explore the health and economic implications of interventions targeting potentially inappropriate prescribing.
EXPLORING VALUES OF HEALTH TECHNOLOGY ASSESSMENT AGENCIES USING REFLECTIVE MULTICRITERIA AND RARE DISEASE CASE
Authors: Goetghebeur Mireille M. , Wagner Monika , Samaha Dima , O'Neil William , Badgley Danielle , Castro-Jaramillo Hector , Abrishami Payam , Sarria-Santamera Antonio , Cleemput Irina , Tringali Michele
Published: October 2017

Objectives: Tackling ethical dilemmas faced by reimbursement decision makers requires deeper understanding of values on which health technology assessment (HTA) agencies are founded and how trade-offs are made. This was explored in this study including the case of rare disease.

Methods: Representatives from eight HTA explored values on which institutions are founded using a narrative approach and reflective multicriteria (developed from EVIDEM, criteria derived from ethical imperatives of health care). Trade-offs between criteria and the impact of incorporating defined priorities (including for rare diseases) were explored through a quantitative values elicitation exercise.

Results: Participants reported a diversity of substantive and procedural values with a common emphasis on scientific excellence, stakeholder involvement, independence, and transparency. Examining the ethical imperatives behind EVIDEM criteria was found to be useful to further explore substantive values. Most criteria were deemed to reflect institutions’ values, while 70 percent of the criteria were reported by at least half of participants to be considered formally by their institutions. The quantitative values elicitation highlighted the difficulty to balance imperatives of “alleviating or preventing patient suffering,” “serving the whole population equitably,” “upholding healthcare system sustainability,” and “making decisions informed by evidence and context” but may help share the ethical reasoning behind decisions. Incorporating “Priorities” (including for rare diseases) helped reveal trade-offs from other criteria and their underlying ethical imperatives.

Conclusions: Reflective multicriteria are useful to explore substantive values of HTAs, reflect how these values and their ethical underpinnings can be operationalized into criteria, and explore the ethical reasoning at the heart of the healthcare debate.
Science for the Chinese Common Reader? Myriad Treasures and New Knowledge at the Turn of the Twentieth Century
Authors: Judge Joan
Published: October 2017

Argument

This article argues that in order to discern the place of science in the epistemology of Chinese common readers, it is critical to look beyond the coastal enclaves where foreign missionaries and experts interacted with Chinese scholars and officials, beyond the translated treatises they produced, and even beyond the various forms of new media that attempted to more widely disseminate the principles of Western science. Instead, it asserts the need to engage a different register of materials that were less directly tied to foreign expertise, more directly in line with pre-existing lineages of printed materials, and at the same time, integral to early-twentieth-century Chinese circuits of information. The article focuses explicitly on one print phenomena that has been completely overlooked in the scholarship to date, the expansion and revitalization of the genre of texts known aswanbao quanshu萬寶全書 (comprehensive compendia of myriad treasures) in the late Qing (1890-1911) and early Republic (1912-1930).
Presentations for (singular) partition monoids: a new approach
Authors: EAST JAMES
Published: October 2017

We give new, short proofs of the presentations for the partition monoid and its singular ideal originally given in the author's 2011 papers inJournal of AlgebraandInternational Journal of Algebra and Computation.
From Hindustan to Brabant: Meyerbeer’s L’africana and Municipal Cosmopolitanism in Post-Unification Italy
Authors: Körner Axel
Published: October 2017

This article examines the political and cultural circumstances leading to the Italian premiere of Giacomo Meyerbeer’s posthumous opera L’Africaine at Bologna’s Teatro Comunale in November 1865. Meyerbeer’s death in May 1864 and the French premiere of his last opera the following year combined to produce a striking moment of transnational cosmopolitan sentiment that built on the composer’s reputation for writing music that had the capacity to communicate across national and political boundaries. Shortly after the Unification of Italy, Bologna was keen to capitalise on these emotions and used the Italian premiere strategically in order to position itself as one of the cultural capitals of the new Italian nation state.
Mohenjo-Daro's Small Public Structures: Heterarchy, Collective Action and a Re-visitation of Old Interpretations with GIS and 3D Modelling
Authors: Green Adam S.
Published: October 2017

Together, the concepts of heterarchy and collective action offer potential explanations for how early state societies may have established high degrees of civic coordination and sophisticated craft industries in the absence of exclusionary political strategies or dominant centralized political hierarchies. The Indus civilization (c. 2600–1900 bc) appears to have been heterarchical, which raises critical questions about how its infrastructure facilitated collective action. Digital re-visitation of early excavation reports provides a powerful means of re-examining the nuances of the resulting datasets and the old interpretations offered to explain them. In an early report on excavations at Mohenjo-daro, the Indus civilization's largest city, Ernest Mackay described a pair of small non-residential structures at a major street intersection as a ‘hostel’ and ‘office’ for the ‘city fathers’. In this article, Mackay's interpretation that these structures had a public orientation is tested using a geographical information systems approach (GIS) and 3D models derived from plans and descriptions in his report. In addition to supporting aspects of Mackay's interpretation, the resulting analysis indicates that Mohenjo-daro's architecture changed through time, increasingly favouring smaller houses and public structures. Close examination of these small public structures also suggests that they may at times have been part of a single complex.
The Greek and Latin Cherubikon
Authors: WANEK NINA-MARIA
Published: October 2017

This article focuses on the so-called ordinary Cherubikon/Cherubic hymn(Οἱ τὰ χερουβίμ/Oi ta Cherubim)found in Byzantine manuscripts in connection with the Divine Liturgies of St John Chrysostomos and St Basil throughout the church year except for Lent and Easter. The Cherubikon is not, however, restricted to Byzantine codices, but can be found in various Latin manuscripts transliterated into Western letters and written with Western neumes.
Language interference and inhibition in early and late successive bilingualism
Authors: PERISTERI ELENI , TSIMPLI IANTHI MARIA , SORACE ANTONELLA , TSAPKINI KYRANA
Published: October 2017

The present study explores whether age of onset of exposure to the second language affects interference resolution at the grammatical gender level and whether cognitive functions contribute to interference resolution. Early and late successive Serbian–Greek bilinguals living in the second language context, along with monolinguals, performed a picture-word interference naming task in a single-language context and a non-verbal inhibition task. We found that gender interference from the first language was only present in late successive bilinguals. Early bilinguals exhibited no interference from the grammatical gender of their mother tongue and showed more enhanced inhibitory abilities than the rest of the groups in the non-verbal task. The distinct sizes of interference from the grammatical gender of the first language across the two bilingual groups is explained by early successive bilinguals’ more enhanced domain-general inhibitory processes in the resolution of between-language conflict at the grammatical gender level relative to late successive bilinguals.
18FDG-PET metabolic response of non-small-cell lung cancer to chemoradiotherapy with long-term follow-up
Authors: Ampil Federico , Caldito Gloria , Richards Troy
Published: October 2017

Aim

18Fluorodeoxyglucose-positron emission tomography (FDG-PET) can indicate the presence or absence of non-small-cell lung cancer (NSCLC) after treatment. We present a description of the FDG-PET results following the contemporary management of locally advanced NSCLC including long-term outcomes.

Methodology

The study participants were eight long-term survivors with metabolic tumour response (MTR) shown on FDG-PET following chemoradiotherapy for locally advanced stage NSCLC between June 2005 and April 2009.

Results

After therapy, MTR was complete in five patients; four subjects were free of cancer, and one patient experienced progression of disease at the time of last follow-up. Of the three individuals with incomplete MTRs, distant metastases developed in two patients, and one subject remained disease-free. Long-term survival ranged from 37 to 75 months.

Conclusion

Although the number of cases is small, our observations confirm the diagnostic role of FDG-PET as well as its value for predicting prognosis in the clinical practice of oncology.
Waterlogging Influence on Roughstalk Bluegrass (Poa trivialis) and Tall Fescue Germination
Authors: Liu Mingyang , Hulting Andrew , Mallory-Smith Carol
Published: October 2017

Oregon’s Willamette Valley is the major cool-season, grass-seed-production area in the world. Roughstalk bluegrass (RB) is a weed in waterlogged, grass-seed-crop fields. Growth chamber and greenhouse studies were conducted to determine the influence of waterlogging on the germination and establishment of RB and tall fescue (TF). Oxygen deficiency resulted in a germination delay in both species, but was greater for TF. Oxygen deficiency at 20 and 30 C was greater for TF compared to RB. Simulated waterlogging for 28 d reduced aboveground biomass more for RB (58%) than for TF (46%), but did not influence seedling survival. Compared to TF, the influence of waterlogging on RB was greater during early establishment. These responses may help RB maintain its germination rate while reducing the damage caused by the accumulation of toxic fermentation-metabolites during waterlogging which benefits RB in competition with TF, especially under high temperatures.
Tolerance of Southern US Rice Cultivars to Benzobicyclon
Authors: Young Mason L. , Norsworthy Jason K. , Scott Robert C. , Barber Lon T.
Published: October 2017

Benzobicyclon is the first 4-hydroxyphenylpyruvate dioxygenase-inhibiting herbicide pursued for commercial registration in U.S. rice production. A study was conducted in 2015 and 2016 to evaluate the response of eight rice cultivars to post-flood application timings of benzobicyclon at 494 g ai ha-1(proposed 2X rate). ‘Caffey’, ‘CL151’, ‘CLXL745’, ‘Jupiter’, ‘LaKast’, ‘Mermentau’, ‘Roy J’, and ‘XL753’ were evaluated in response to applications of benzobicyclon. The highest level of visible injury was observed in LaKast at 7% in 2015. No visible injury was detected among other cultivars either year at 2 weeks after treatment. In 2015 and 2016, no more than a four-day delay to reach 50% heading occurred across all cultivars. Rough rice yield was not affected by any of the post-flood application timings of benzobicyclon. A second study was conducted in 2016 at three locations throughout Arkansas to investigate the tolerance of 19tropical japonica(inbred and hybrid) and twoindicainbred cultivars to a premix containing benzobicyclon at 494 g ai ha-1and halosulfuron at 72 g ai ha-1 applied 1 week after flooding. Thetropical japonicacultivars have excellent crop safety to benzobicyclon while application to theindicacultivars, Rondo and Purple Marker, expressed severe phytotoxicity. Benzobicyclon caused less than a 2 d delay in heading to thejaponicacultivars. Rough rice yield of thetropical japonicacultivars was not affected by benzobicyclon while yields of bothindicacultivars were negatively affected. Benzobicyclon can safely be applied to drill-seededtropical japonicainbred and hybrid cultivars in a post-flood application without concerns for crop injury. Benzobicyclon should not be used onindicacultivars as it will cause severe injury, delayed heading, and yield loss.
Probing the Cusps of Saturn’s Magnetic Field
Authors: Zastrow Mark
Published: October 2017

Data from the Cassini spacecraft show that the cusp regions of Saturn’s magnetic field—where it connects to the Sun’s magnetic field—have similarities to Earth’s and also intriguing differences.
Plasmonic tunnel junctions for single-molecule redox chemistry
Authors: de Nijs Bart , Benz Felix , Barrow Steven J. , Sigle Daniel O. , Chikkaraddy Rohit , Palma Aniello , Carnegie Cloudy , Kamp Marlous , Sundararaman Ravishankar , Narang Prineha , Scherman Oren A. , Baumberg Jeremy J.
Published: October 2017

Nanoparticles attached just above a flat metallic surface can trap optical fields in the nanoscale gap. This enables local spectroscopy of a few molecules within each coupled plasmonic hotspot, with near thousand-fold enhancement of the incident fields. As a result of non-radiative relaxation pathways, the plasmons in such sub-nanometre cavities generate hot charge carriers, which can catalyse chemical reactions or induce redox processes in molecules located within the plasmonic hotspots. Here, surface-enhanced Raman spectroscopy allows us to track these hot-electron-induced chemical reduction processes in a series of different aromatic molecules. We demonstrate that by increasing the tunnelling barrier height and the dephasing strength, a transition from coherent to hopping electron transport occurs, enabling observation of redox processes in real time at the single-molecule level.
Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease
Authors: Deng Ruishu , Hurtz Christian , Song Qingxiao , Yue Chanyu , Xiao Gang , Yu Hua , Wu Xiwei , Muschen Markus , Forman Stephen , Martin Paul J. , Zeng Defu
Published: October 2017

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome mediated by pathogenic CD4+T and B cells, but the function of extrafollicular and germinal center CD4+T and B interactions in cGVHD pathogenesis remains largely unknown. Here we show that extrafollicular CD4+T and B interactions are sufficient for inducing cGVHD, while germinal center formation is dispensable. The pathogenesis of cGVHD is associated with the expansion of extrafollicular CD44hiCD62loPSGL-1loCD4+(PSGL-1loCD4+) T cells. These cells express high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and ameliorates cGVHD. Expansion of PSGL-1loCD4+T cells is also prevented by BCL6 or Stat3 deficiency in donor CD4+T cells, with the induction of cGVHD ameliorated by BCL6 deficiency and completely suppressed by Stat3 deficiency in donor CD4+T cells. These results support that Stat3- and BCL6-dependent extrafollicular CD4+T and B interactions play critical functions in the pathogenesis of cGVHD.
Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain
Authors: Anraku Y. , Kuwahara H. , Fukusato Y. , Mizoguchi A. , Ishii T. , Nitta K. , Matsumoto Y. , Toh K. , Miyata K. , Uchida S. , Nishina K. , Osada K. , Itaka K. , Nishiyama N. , Mizusawa H. , Yamasoba T. , Yokota T. , Kataoka K.
Published: October 2017

Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.
Enhanced generation and anisotropic Coulomb scattering of hot electrons in an ultra-broadband plasmonic nanopatch metasurface
Authors: Sykes Matthew E. , Stewart Jon W. , Akselrod Gleb M. , Kong Xiang-Tian , Wang Zhiming , Gosztola David J. , Martinson Alex B. F. , Rosenmann Daniel , Mikkelsen Maiken H. , Govorov Alexander O. , Wiederrecht Gary P.
Published: October 2017

The creation of energetic electrons through plasmon excitation of nanostructures before thermalization has been proposed for a wide number of applications in optical energy conversion and ultrafast nanophotonics. However, the use of “nonthermal” electrons is primarily limited by both a low generation efficiency and their ultrafast decay. We report experimental and theoretical results on the use of broadband plasmonic nanopatch metasurfaces comprising a gold substrate coupled to silver nanocubes that produce large concentrations of hot electrons, which we measure using transient absorption spectroscopy. We find evidence for three subpopulations of nonthermal carriers, which we propose arise from anisotropic electron–electron scattering within sp-bands near the Fermi surface. The bimetallic character of the metasurface strongly impacts the physics, with dissipation occurring primarily in the gold, whereas the quantum process of hot electron generation takes place in both components. Our calculations show that the choice of geometry and materials is crucial for producing strong ultrafast nonthermal electron components.
Mass spectrometry sequencing of long digital polymers facilitated by programmed inter-byte fragmentation
Authors: Al Ouahabi Abdelaziz , Amalian Jean-Arthur , Charles Laurence , Lutz Jean-François
Published: October 2017

In the context of data storage miniaturization, it was recently shown that digital information can be stored in the monomer sequences of non-natural macromolecules. However, the sequencing of such digital polymers is currently limited to short chains. Here, we report that intact multi-byte digital polymers can be sequenced in a moderate resolution mass spectrometer and that full sequence coverage can be attained without requiring pre-analysis digestion or the help of sequence databases. In order to do so, the polymers are designed to undergo controlled fragmentations in collision-induced dissociation conditions. Each byte of the sequence is labeled by an identification tag and a weak alkoxyamine group is placed between 2 bytes. As a consequence of this design, the NO-C bonds break first upon collisional activation, thus leading to a pattern of mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in pseudo-MS3 conditions and the whole sequence is found.
Quantum sensing of weak radio-frequency signals by pulsed Mollow absorption spectroscopy
Authors: Joas T. , Waeber A. M. , Braunbeck G. , Reinhard F.
Published: October 2017

Quantum sensors—qubits sensitive to external fields—have become powerful detectors for various small acoustic and electromagnetic fields. A major key to their success have been dynamical decoupling protocols which enhance sensitivity to weak oscillating (AC) signals. Currently, those methods are limited to signal frequencies below a few MHz. Here we harness a quantum-optical effect, the Mollow triplet splitting of a strongly driven two-level system, to overcome this limitation. We microscopically understand this effect as a pulsed dynamical decoupling protocol and find that it enables sensitive detection of fields close to the driven transition. Employing a nitrogen-vacancy center, we detect GHz microwave fields with a signal strength (Rabi frequency) below the current detection limit, which is set by the center’s spectral linewidth $$1{\rm{/}}T_2^*$$
1
∕

T

2

*

. Pushing detection sensitivity to the much lower 1/T2 limit, this scheme could enable various applications, most prominently coherent coupling to single phonons and microwave photons.
Anomeric memory of the glycosidic bond upon fragmentation and its consequences for carbohydrate sequencing
Authors: Schindler Baptiste , Barnes Loïc , Renois Gina , Gray Christopher , Chambert Stéphane , Fort Sébastien , Flitsch Sabine , Loison Claire , Allouche Abdul-Rahman , Compagnon Isabelle
Published: October 2017

Deciphering the carbohydrate alphabet is problematic due to its unique complexity among biomolecules. Strikingly, routine sequencing technologies—which are available for proteins and DNA and have revolutionised biology—do not exist for carbohydrates. This lack of structural tools is identified as a crucial bottleneck, limiting the full development of glycosciences and their considerable potential impact for the society. In this context, establishing generic carbohydrate sequencing methods is both a major scientific challenge and a strategic priority. Here we show that a hybrid analytical approach integrating molecular spectroscopy with mass spectrometry provides an adequate metric to resolve carbohydrate isomerisms, i.e the monosaccharide content, anomeric configuration, regiochemistry and stereochemistry of the glycosidic linkage. On the basis of the spectroscopic discrimination of MS fragments, we report the unexpected demonstration of the anomeric memory of the glycosidic bond upon fragmentation. This remarkable property is applied to de novo sequencing of underivatized oligosaccharides.
Nanoscale control of competing interactions and geometrical frustration in a dipolar trident lattice
Authors: Farhan Alan , Petersen Charlotte F. , Dhuey Scott , Anghinolfi Luca , Qin Qi Hang , Saccone Michael , Velten Sven , Wuth Clemens , Gliga Sebastian , Mellado Paula , Alava Mikko J. , Scholl Andreas , van Dijken Sebastiaan
Published: October 2017

Geometrical frustration occurs when entities in a system, subject to given lattice constraints, are hindered to simultaneously minimize their local interactions. In magnetism, systems incorporating geometrical frustration are fascinating, as their behavior is not only hard to predict, but also leads to the emergence of exotic states of matter. Here, we provide a first look into an artificial frustrated system, the dipolar trident lattice, where the balance of competing interactions between nearest-neighbor magnetic moments can be directly controlled, thus allowing versatile tuning of geometrical frustration and manipulation of ground state configurations. Our findings not only provide the basis for future studies on the low-temperature physics of the dipolar trident lattice, but also demonstrate how this frustration-by-design concept can deliver magnetically frustrated metamaterials.
Paraquat and MPTP induce neurodegeneration and alteration in the expression profile of microRNAs: the role of transcription factor Nrf2
Authors: Wang Qingqing , Ren Nan , Cai Zhipeng , Lin Qingxia , Wang Zhangjing , Zhang Qunwei , Wu Siying , Li Huangyuan
Published: October 2017

Both transcription factors (TFs) and microRNAs (miRNAs) can exert a widespread impact on gene expression. In the present study, we investigated the role of Nrf2 in paraquat-induced intracorporeal neurodegeneration and miRNA expression by exposing Nrf2 wild-type and knockout mice to paraquat (PQ) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exposure to 10 mg/kg PQ or 30 mg/kg MPTP caused damage to nerve cells in the substantia nigra (SN) in both Nrf2 (+/+) and Nrf2 (−/−) ICR mice, which included cell morphological changes, detectable apoptosis and a significant reduction in the number of dopaminergic (DA) neurons. When mice were exposed to the same PQ dose of 10 mg/kg, significant fewer tyrosine hydroxylase (TH)-positive DA neurons were observed in the Nrf2 (−/−) mice than that in the Nrf2 (+/+) mice. Both Nrf2 deficiency and PQ or MPTP exposure could alter miRNA expression profile in the SN, suggesting the potential involvement of Nrf2 in the PQ-induced or MPTP-induced miRNA expression alteration. The expression of miR-380-3p was altered by the Nrf2-MPTP interaction effect. miR-380-3p/Sp3-mRNA pathway is likely part of the mechanism of MPTP-induced neurodegeneration. Collectively, our results corroborated the protective role of Nrf2 and also demonstrated the essential interaction of Nrf2 with miRNAs in intracorporal neurodegeneration induced by neurotoxicants.
Dual-source Computed Tomography for Evaluating Pulmonary Artery and Aorta in Pediatric Patients with Single Ventricle
Authors: Yang Meng-xi , Yang Zhi-gang , Zhang Yi , Shi Ke , Xu Hua-yan , Diao Kai-yue , Guo Ying-kun
Published: October 2017

To explore the accuracy of main pulmonary artery (MPA) and ascending aorta (AAO) image evaluation in pediatric patients with single ventricle (SV) by comparing dual-source computed tomography (DSCT) with echocardiography. Thirty-one children with SV were retrospectively enrolled. The stenosis, dilation, and location of MPA and AAO were independently evaluated by DSCT and echocardiography. The accompanying arterial malformations were also assessed by DSCT. For 17 patients undergoing cardiac catheterization, the DSCT-based diameters of MPA and AAO were correlated with their pressures as measured by catheterization. Referring to the surgical and catheterization findings, DSCT had better diagnostic performance in detecting the stenosis, dilation, and location of MPA and AAO with higher sensitivity than echocardiography (sensitivity, MPA: 88.0% vs. 80.0%, AAO: 100% vs. 66.7%, great arteries location: 95.7% vs. 95.2%). The correlations between diameters of MPA and AAO with their pressures were 0.399 (p = 0.04) and 0.611 (p = 0.01), respectively. In addition, DSCT detected 23 cases with patent ductus arteriosus, 26 systemic-to-pulmonary collaterals, 9 branch pulmonary distortions, and 4 coronary artery anomalies. DSCT is reliable for assessing the anatomic features of pulmonary artery and aorta in SV children, and provides comprehensive information for surgical strategy-making.
Knot Energy, Complexity, and Mobility of Knotted Polymers
Authors: Vargas–Lara Fernando , Hassan Ahmed M. , Mansfield Marc L. , Douglas Jack F.
Published: October 2017

The Coulomb energy EC is defined by the energy required to charge a conductive object and scales inversely to the self–capacity C, a basic measure of object size and shape. It is known that C is minimized for a sphere for all objects having the same volume, and that C increases as the symmetry of an object is reduced at fixed volume. Mathematically similar energy functionals have been related to the average knot crossing number 〈m〉, a natural measure of knot complexity and, correspondingly, we find EC to be directly related to 〈m〉 of knotted DNA. To establish this relation, we employ molecular dynamics simulations to generate knotted polymeric configurations having different length and stiffness, and minimum knot crossing number values m for a wide class of knot types relevant to the real DNA. We then compute EC for all these knotted polymers using the program ZENO and find that the average Coulomb energy 〈EC〉 is directly proportional to 〈m〉. Finally, we calculate estimates of the ratio of the hydrodynamic radius, radius of gyration, and the intrinsic viscosity of semi–flexible knotted polymers in comparison to the linear polymeric chains since these ratios should be useful in characterizing knotted polymers experimentally.
Handheld Photoacoustic Microscopy Probe
Authors: Park Kyungjin , Kim Jin Young , Lee Changho , Jeon Seungwan , Lim Geunbae , Kim Chulhong
Published: October 2017

Optical resolution photoacoustic microscopy (OR-PAM) is a non-invasive, label-free method of in vivo imaging with microscopic resolution and high optical contrast. Based on intrinsic contrasts, OR-PAM has expanded to include in vivo vessel imaging, flow cytometry, physiological parameter analysis, and single-cell characterization. However, since conventional OR-PAM systems have a fixed tabletop configuration, a large system size, and slow imaging speed, their use in preclinical and clinical studies remains limited. In this study, using microelectromechanical systems (MEMS) technology, we developed a handheld PAM probe with a high signal-to-noise ratio and image rate. To enable broader application of the OR-PAM system, we reduced its size and combined its fast scanning capabilities into a small handheld probe that uses a 2-axis waterproof MEMS scanner (2A-WP-MEMS scanner). All acoustical, optical, and mechanical components are integrated into a single probe with a diameter of 17 mm and a weight of 162 g. This study shows phantom and in vivo images of various samples acquired with the probe, including carbon fibers, electrospun microfibers, and the ear, iris, and brain of a living mouse. In particular, this study investigated the possibility of clinical applications for melanoma diagnosis by imaging the boundaries and morphology of a human mole.
β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development
Authors: Ling Yue-Ming , Chen Jin-Yu , Guo Libin , Wang Chen-Yi , Tan Wen-Ting , Wen Qing , Zhang Shu-Dong , Deng Guo-Hong , Lin Yao , Kwok Hang Fai
Published: October 2017

β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development.
Host heterozygosity and genotype rarity affect viral dynamics in an avian subspecies complex
Authors: Eastwood Justin R. , Ribot Raoul F. H. , Rollins Lee Ann , Buchanan Katherine L. , Walder Ken , Bennett Andrew T. D. , Berg Mathew L.
Published: October 2017

Genetic diversity at community, population and individual levels is thought to influence the spread of infectious disease. At the individual level, inbreeding and heterozygosity are associated with increased risk of infection and disease severity. Host genotype rarity may also reduce infection risk if pathogens are co-adapted to common or local hosts, but to date, no studies have investigated the relative importance of genotype rarity and heterozygosity for infection in a wild, sexually reproducing vertebrate. With beak and feather disease virus (BFDV) infection in a wild parrot (Platycercus elegans), we show that both heterozygosity and genotype rarity of individual hosts predicted infection, but in contrasting ways. Heterozygosity was negatively associated with probability of infection, but not with infection load. In contrast, increased host genotype rarity was associated with lower viral load in infected individuals, but did not predict infection probability. These effects were largely consistent across subspecies, but were not evident at the population level. Subspecies and age were also strongly associated with infection. Our study provides novel insights into infection dynamics by quantifying rarity and diversity simultaneously. We elucidate roles that host genetic diversity can play in infection dynamics, with implications for understanding population divergence, intraspecific diversity and conservation.
Size Variation under Domestication: Conservatism in the inner ear shape of wolves, dogs and dingoes
Authors: Schweizer Anita V. , Lebrun Renaud , Wilson Laura A. B. , Costeur Loïc , Schmelzle Thomas , Sánchez-Villagra Marcelo R.
Published: October 2017

A broad sample of wolves, dingoes, and domesticated dogs of different kinds and time periods was used to identify changes in size and shape of the organs of balance and hearing related to domestication and to evaluate the potential utility of uncovered patterns as markers of domestication. Using geometric morphometrics coupled with non-invasive imaging and three-dimensional reconstructions, we exposed and compared complex structures that remain largely conserved. There is no statistically significant difference in the levels of shape variation between prehistoric and modern dogs. Shape variance is slightly higher for the different components of the inner ear in modern dogs than in wolves, but these differences are not significant. Wolves express a significantly greater level of variance in the angle between the lateral and the posterior canal than domestic dog breeds. Wolves have smaller levels of size variation than dogs. In terms of the shape of the semicircular canals, dingoes reflect the mean shape in the context of variation in the sample. This mirrors the condition of feral forms in other organs, in which there is an incomplete return to the characteristics of the ancestor. In general, morphological diversity or disparity in the inner ear is generated by scaling.
Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors
Authors: Bogusz Jozefina , Zrubek Karol , Rembacz Krzysztof P. , Grudnik Przemyslaw , Golik Przemyslaw , Romanowska Malgorzata , Wladyka Benedykt , Dubin Grzegorz
Published: October 2017

PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Two of the reported structures (CX-4945 and Ro-3306) explain the off-target effect on PIM1 of respectively casein kinase 2 and cyclin-dependent kinase 1 dedicated inhibitors. In turn, the structure with CX-6258 demonstrates a binding mode of a potent, selective inhibitor of PIM1, PIM2, PIM3 and Flt-3 kinases. The consequences of our findings for future inhibitor development are discussed.
Efficient induction of comprehensive immune responses to control pathogenic E. coli by clay nano-adjuvant with the moderate size and surface charge
Authors: Chen Weiyu , Zuo Huali , Mahony Timothy J. , Zhang Bing , Rolfe Barbara , Xu Zhi Ping
Published: October 2017

In recent decades, diseases caused by pathogenic Escherichia coli (E. coli), enterohaemorrhagic E. coli (EHEC) O26 have been increasingly reported worldwide, which are as severe as those caused by EHEC strain O157:H7 and require effective intervention strategies. Herein, we report the application of clay nanoparticles, i.e. hectorites as effective nano-adjuvants for vaccination against EHEC O26 colonization. We show that medium size HEC (hectorite, around 73~77 nm diameter) is able to induce efficient humoral and cellular immune responses against EHEC antigen - intimin β (IB), which are significantly higher than those triggered by commercially used adjuvants - QuilA and Alum. We also demonstrate that mice immunized with IB adjuvanted with HEC nanoparticles elicit sufficient secretion of mucosal IgA, capable of providing effective protection against EHEC O26 binding to ruminant and human cells. In addition, we demonstrate for the first time that hectorites are able to initiate maturation of RAW 264.7 macrophages, inducing expression of co-stimulatory cytokines at a low nanoparticle concentration (10 μg/mL). Together these data strongly suggest that hectorite with optimized size is a highly efficient vaccine nano-adjuvant.
A Microscopic Shell Structure with Schwarz’s D-Surface
Authors: Han Seung Chul , Choi Jeong Myung , Liu Gang , Kang Kiju
Published: October 2017

Recently, materials with micro-architecture of hollow trusses and ultralow density (less than 10–2 Mg/m3) have gained attention. The materials have been fabricated by forming templates based on 3D lithographical techniques, followed by hard coating on the surface, and finally etching out the template. Here, we describe a novel fabrication method for another micro architecture composed of a single continuous smooth-curved shell with D-surface, named Shellular; its template is prepared based on weaving flexible polymer wires. Compression test results reveal that these D-surfaced Shellulars have strength and Young’s modulus comparable to those of their hollow truss-based competitors. The best virtue of this weaving-based technology is its mass-productivity and large-size potential. Also, this technology can be applied to fabricate not only D-surfaced but also P- or G-surfaced Shellular. The unique geometry of Shellular, composed of a single continuous, smooth, and interfacial shell or membrane separating two equivalent sub-volumes intertwined with each other, appears to possess huge application potential such as non-clogging tissue engineering scaffolds and compact light-weight fuel cells with high energy density.
Bone Microarchitecture and Biomechanics of the Necrotic Femoral Head
Authors: Ma Jian-xiong , He Wei-wei , Zhao Jie , Kuang Ming-jie , Bai Hao-hao , Sun Lei , Lu Bin , Tian Ai-xian , Wang Ying , Dong Ben-chao , Wang Yan , Ma Xin-long
Published: October 2017

The mechanism behind osteonecrosis of the femoral head (ONFH) remains unclear. The aim of this study was to explore the pathogenesis of ONFH from a biomechanical standpoint to provide a theoretical basis for improved treatments. We compared the bone structure of fractured femoral heads with that of necrotic femoral heads by Micro-CT scanning and histological evaluation. In addition, we compared the biomechanical properties of each zone in fractured femoral heads with those in necrotic femoral heads by using biomechanical tests. Compared with fractured femoral heads, bone microarchitecture and bone morphometry in necrotic zone and sclerotic zone of necrotic femoral heads have altered markedly. In addition, the biomechanical properties of the necrotic zone in femoral heads weaken markedly, while those of the sclerotic zone strengthen. We hypothesize that discordance between bone structure and function of the femoral head may be involved in the pathogenesis of ONFH and that more attention should be paid to the prevention and treatment of such discordance.
GLRB variants regulate nearby gene expression in human brain tissues
Authors: Wu Qing-jian , Yang Ming-feng , Hao Pi-da , Yan Cheng-jun , Du Chun-jing , Li Han-xia , Hou Ya-jun , Sun Bao-liang , Sun Shu-yin
Published: October 2017

A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.
Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase IIα and Rap1
Authors: Cornelia Koeberle Solveigh , Tanaka Shinji , Kuriu Toshihiko , Iwasaki Hirohide , Koeberle Andreas , Schulz Alexander , Helbing Dario-Lucas , Yamagata Yoko , Morrison Helen , Okabe Shigeo
Published: October 2017

The roles of calcium-calmodulin-dependent protein kinase II-alpha (CaMKIIα) in the expression of long-term synaptic plasticity in the adult brain have been extensively studied. However, how increased CaMKIIα activity controls the maturation of neuronal circuits remains incompletely understood. Herein, we show that pyramidal neurons without CaMKIIα activity upregulate the rate of spine addition, resulting in elevated spine density. Genetic elimination of CaMKIIα activity specifically eliminated the observed maturation-dependent suppression of spine formation. Enhanced spine formation was associated with the stabilization of actin in the spine and could be reversed by increasing the activity of the small GTPase Rap1. CaMKIIα activity was critical in the phosphorylation of synaptic Ras GTPase-activating protein (synGAP), the dispersion of synGAP from postsynaptic sites, and the activation of postsynaptic Rap1. CaMKIIα is already known to be essential in learning and memory, but our findings suggest that CaMKIIα plays an important activity-dependent role in restricting spine density during postnatal development.
Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide
Authors: Dodacki Agnès , Wortman Matthew , Saubaméa Bruno , Chasseigneaux Stéphanie , Nicolic Sophie , Prince Nathalie , Lochus Murielle , Raveu Anne-Laure , Declèves Xavier , Scherrmann Jean-Michel , Patel Shailendra B. , Bourasset Fanchon
Published: October 2017

ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamically favorable binding at the putative sterol-binding site, and this was greater than for cholesterol. Additionally, unbiased docking also showed Aβ binding at this site. Using a novel Abcg4-deficient mouse model, we show that Abcg4 was able to export Aβ and desmosterol at the BBB level and these processes could be inhibited by probucol and L-thyroxine. Our assay also showed that desmosterol antagonized the export of Aβ, presumably as both bind at the sterol-binding site on Abcg4. We show for the first time that Abcg4 may function in vivo to export Aβ at the BBB, in a process that can be antagonized by its putative natural ligand, desmosterol (and possibly cholesterol).
Composition-dependent nanoelectronics of amido-phenazines: non-volatile RRAM and WORM memory devices
Authors: Maiti Dilip K. , Debnath Sudipto , Nawaz Sk. Masum , Dey Bapi , Dinda Enakhi , Roy Dipanwita , Ray Sudipta , Mallik Abhijit , Hussain Syed A.
Published: October 2017

A metal-free three component cyclization reaction with amidation is devised for direct synthesis of DFT-designed amido-phenazine derivative bearing noncovalent gluing interactions to fabricate organic nanomaterials. Composition-dependent organic nanoelectronics for nonvolatile memory devices are discovered using mixed phenazine-stearic acid (SA) nanomaterials. We discovered simultaneous two different types of nonmagnetic and non-moisture sensitive switching resistance properties of fabricated devices utilizing mixed organic nanomaterials: (a) sample-1(8:SA = 1:3) is initially off, turning on at a threshold, but it does not turn off again with the application of any voltage, and (b) sample-2 (8:SA = 3:1) is initially off, turning on at a sharp threshold and off again by reversing the polarity. No negative differential resistance is observed in either type. These samples have different device implementations: sample-1 is attractive for write-once-read-many-times memory devices, such as novel non-editable database, archival memory, electronic voting, radio frequency identification, sample-2 is useful for resistive-switching random access memory application.