bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals
Authors: Bos Jacqueline M. , Natsch Stephanie , van den Bemt Patricia M. L. A. , Pot Johan L. W. , Nagtegaal J. Elsbeth , Wieringa Andre , van der Wilt Gert Jan , De Smet Peter A. G. M. , Kramers Cornelis 
Published: November 2017

AbstractBackground Despite the potential of clinical practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before–after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain management, antithrombotics, fluid and electrolyte management, prescribing in case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophylaxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consultations, combining medication review of patients who are at risk for drug related problems with visits to ward physicians. Main outcome measure The outcome measure was the proportion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49–0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.
Results of pediatric endoscopic and endoscopically assisted tympanoplasty
Authors: Isaacson Glenn , Harounian Jonathan A. 
Published: November 2017

ObjectivesTo evaluate the success of pediatric endoscopic and endoscopically assisted transcanal cartilage inlay tympanoplasty.MethodsRetrospective review of single surgeon experience.ResultsDuring a 3 year period, 30 children underwent 31 endoscopic or endoscopically assisted transcanal tympanoplasties by the senior surgeon using tragal cartilage/perichondrial inlay grafts. There were 22 boys and 8 girls, ranging in age from 3.5 to 17 years (median 6 years). All tragal cartilage grafts (31/31; 100%) survived. Twenty‐seven surgeries (27/31; 82%) resulted in an intact drum (17/31; 55%) or a microperforation (10/31; 32%). In four cases (4/31; 13%) significant perforations formed in previously unaffected portions of the drum.ConclusionTranscanal endoscopic cartilage inlay tympanoplasty offers a practical, minimally invasive approach to tympanoplasty for children of any age. It avoids postauricular or endaural incisions, tympanomeatal flap elevation, and canalplasty. Graft survival is uniform. Microperforation at the graft margins remained in 1/3 of children. Technical modifications may lead to higher rates of tympanic closure.
Aging and Frailty in First Nations Communities
Authors:   First Nations Information Governance Centre, Walker Jennifer D. 
Published: November 2017

ABSTRACTThis study, the first published overview of aging in a nationally representative sample of First Nations seniors, used data from the First Nations Regional Health Survey Phase 2 (FNRHS 2). It is also the first application of a validated frailty index to describe aging experiences in First Nations communities. Responding to the survey were 11,043 First Nations adults. Of the 1,820 First Nations seniors who responded, 52.7 per cent (95% CI [49.4−56.1]) were not frail. The maintenance of non-frail status in First Nations adults appeared to decrease in each middle-adult age group (from 87.9% in ages 35–44 through to 63.1% in ages 55–64) and to plateau after age 65. The findings are a key step in documenting the experiences of First Nations seniors nationally from a First Nations perspective. They also highlight the key need for supportive health services and chronic disease management at younger ages.
The bacterium Wolbachia exploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquito Aedes aegypti
Authors: Pan Xiaoling , Pike Andrew , Joshi Deepak , Bian Guowu , McFadden Michael J , Lu Peng , Liang Xiao , Zhang Fengrui , Raikhel Alexander S , Xi Zhiyong 
Published: November 2017

Abstract
A host’s immune system plays a central role in shaping the composition of the microbiota and, in return, resident microbes influence immune responses. Symbiotic associations of the maternally transmitted bacterium Wolbachia occur with a wide range of arthropods. It is, however, absent from the dengue and Zika vector mosquito Aedes aegypti in nature. When Wolbachia is artificially forced to form symbiosis with this new mosquito host, it boosts the basal immune response and enhances the mosquito’s resistance to pathogens, including dengue, Zika virus and malaria parasites. The mechanisms involved in establishing a symbiotic relationship between Wolbachia and A. aegypti, and the long-term outcomes of this interaction, are not well understood. Here, we have demonstrated that both the immune deficiency (IMD) and Toll pathways are activated by the Wolbachia strain wAlbB upon its introduction into A. aegypti. Silencing the Toll and IMD pathways via RNA interference reduces the wAlbB load. Notably, wAlbB induces peptidoglycan recognition protein (PGRP)-LE expression in the carcass of A. aegypti, and its silencing results in a reduction of symbiont load. Using transgenic mosquitoes with stage-specific induction of the IMD and Toll pathways, we have shown that elevated wAlbB infection in these mosquitoes is maintained via maternal transmission. These results indicate that host innate immunity is utilized to establish and promote host-microbial symbiosis. Our results will facilitate a long-term projection of the stability of the Wolbachia–A. aegypti mosquito system that is being developed to control dengue and Zika virus transmission to humans.
Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent
Authors: Wang Pengju , Li Xiaozhu , Wang Jiwei , Gao Dongling , Li Yuenan , Li Haoze , Chu Yongchao , Zhang Zhongxian , Liu Hongtao , Jiang Guozhong , Cheng Zhenguo , Wang Shengdian , Dong Jianzeng , Feng Baisui , Chard Louisa S. , Lemoine Nicholas R. , Wang Yaohe 
Published: November 2017

AbstractInterleukin-12 (IL-12) has emerged as one of the most potent agents for anti-tumor immunotherapy. However, potentially lethal toxicity associated with systemic administration of IL-12 precludes its clinical application. Here we redesign the molecule in such a way that its anti-tumor efficacy is not compromised, but toxic effects are eliminated. Deletion of the N-terminal signal peptide of IL-12 can effect such a change by preventing IL-12 secretion from cells. We use a newly designed tumor-targeted oncolytic adenovirus (Ad-TD) to deliver non-secreting (ns) IL-12 to tumor cells and examine the therapeutic and toxic effects in Syrian hamster models of pancreatic cancer (PaCa). Strikingly, intraperitoneal delivery of Ad-TD-nsIL-12 significantly enhanced survival of animals with orthotopic PaCa and cured peritoneally disseminated PaCa with no toxic side effects, in contrast to the treatment with Ad-TD expressing unmodified IL-12. These findings offer renewed hope for development of IL-12-based treatments for cancer.
Effect of nitrogen atom positioning on the trade-off between emissive and photocatalytic properties of carbon dots
Authors: Bhattacharyya Santanu , Ehrat Florian , Urban Patrick , Teves Roland , Wyrwich Regina , Döblinger Markus , Feldmann Jochen , Urban Alexander S. , Stolarczyk Jacek K. 
Published: November 2017

AbstractCarbon dots (CDs) are a versatile nanomaterial with attractive photoluminescent and photocatalytic properties. Here we show that these two functionalities can be easily tuned through a simple synthetic means, using a microwave irradiation, with citric acid and varying concentrations of nitrogen-containing branched polyethyleneimine (BPEI) as precursors. The amount of BPEI determines the degree of nitrogen incorporation and the different inclusion modes within the CDs. At intermediate levels of BPEI, domains grow containing mainly graphitic nitrogen, producing a high photoluminescence yield. For very high (and very low) BPEI content, the nitrogen atoms are located primarily at the edge sites of the aromatic domains. Accordingly, they attract photogenerated electrons, enabling efficient charge separation and enhanced photocatalytic hydrogen generation from water. The ensuing ability to switch between emissive and photocatalytic behavior of CDs is expected to bring substantial improvements on their efficiency for on-demand light emission or energy conversion applications.
Structural insights into DNA cleavage activation of CRISPR-Cas9 system
Authors: Huai Cong , Li Gan , Yao Ruijie , Zhang Yingyi , Cao Mi , Kong Liangliang , Jia Chenqiang , Yuan Hui , Chen Hongyan , Lu Daru , Huang Qiang 
Published: November 2017

AbstractCRISPR-Cas9 technology has been widely used for genome engineering. Its RNA-guided endonuclease Cas9 binds specifically to target DNA and then cleaves the two DNA strands with HNH and RuvC nuclease domains. However, structural information regarding the DNA cleavage-activating state of two nuclease domains remains sparse. Here, we report a 5.2 Å cryo-EM structure of Cas9 in complex with sgRNA and target DNA. This structure reveals a conformational state of Cas9 in which the HNH domain is closest to the DNA cleavage site. Compared with two known HNH states, our structure shows that the HNH active site moves toward the cleavage site by about 25 and 13 Å, respectively. In combination with EM-based molecular dynamics simulations, we show that residues of the nuclease domains in our structure could form cleavage-compatible conformations with the target DNA. Together, these results strongly suggest that our cryo-EM structure resembles a DNA cleavage-activating architecture of Cas9.
Depleted depletion drives polymer swelling in poor solvent mixtures
Authors: Mukherji Debashish , Marques Carlos M. , Stuehn Torsten , Kremer Kurt 
Published: November 2017

AbstractEstablishing a link between macromolecular conformation and microscopic interaction is a key to understand properties of polymer solutions and for designing technologically relevant “smart” polymers. Here, polymer solvation in solvent mixtures strike as paradoxical phenomena. For example, when adding polymers to a solvent, such that all particle interactions are repulsive, polymer chains can collapse due to increased monomer–solvent repulsion. This depletion induced monomer–monomer attraction is well known from colloidal stability. A typical example is poly(methyl methacrylate) (PMMA) in water or small alcohols. While polymer collapse in a single poor solvent is well understood, the observed polymer swelling in mixtures of two repulsive solvents is surprising. By combining simulations and theoretical concepts known from polymer physics and colloidal science, we unveil the microscopic, generic origin of this collapse–swelling–collapse behavior. We show that this phenomenon naturally emerges at constant pressure when an appropriate balance of entropically driven depletion interactions is achieved.
Electromagnetic scattering laws in Weyl systems
Authors: Zhou Ming , Ying Lei , Lu Ling , Shi Lei , Zi Jian , Yu Zongfu 
Published: November 2017

AbstractWavelength determines the length scale of the cross section when electromagnetic waves are scattered by an electrically small object. The cross section diverges for resonant scattering, and diminishes for non-resonant scattering, when wavelength approaches infinity. This scattering law explains the colour of the sky as well as the strength of a mobile phone signal. We show that such wavelength scaling comes from the conical dispersion of free space at zero frequency. Emerging Weyl systems, offering similar dispersion at non-zero frequencies, lead to new laws of electromagnetic scattering that allow cross sections to be decoupled from the wavelength limit. Diverging and diminishing cross sections can be realized at any target wavelength in a Weyl system, providing the ability to tailor the strength of wave–matter interactions for radiofrequency and optical applications.
The self-healing of defects induced by the hydriding phase transformation in palladium nanoparticles
Authors: Ulvestad A. , Yau A. 
Published: November 2017

AbstractNanosizing can dramatically alter material properties by enhancing surface thermodynamic contributions, shortening diffusion lengths, and increasing the number of catalytically active sites per unit volume. These mechanisms have been used to explain the improved properties of catalysts, battery materials, plasmonic materials, etc. Here we show that Pd nanoparticles also have the ability to self-heal defects in their crystal structures. Using Bragg coherent diffractive imaging, we image dislocations nucleated deep in a Pd nanoparticle during the forward hydriding phase transformation that heal during the reverse transformation, despite the region surrounding the dislocations remaining in the hydrogen-poor phase. We show that defective Pd nanoparticles exhibit sloped isotherms, indicating that defects act as additional barriers to the phase transformation. Our results resolve the formation and healing of structural defects during phase transformations at the single nanoparticle level and offer an additional perspective as to how and why nanoparticles differ from their bulk counterparts.
A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer
Authors: Li Fangfei , Lu Jun , Liu Jin , Liang Chao , Wang Maolin , Wang Luyao , Li Defang , Yao Houzong , Zhang Qiulong , Wen Jia , Zhang Zong-Kang , Li Jie , Lv Quanxia , He Xiaojuan , Guo Baosheng , Guan Daogang , Yu Yuanyuan , Dang Lei , Wu Xiaohao , Li Yongshu , Chen Guofen , Jiang Feng , Sun Shiguo , Zhang Bao-Ting , Lu Aiping , Zhang Ge 
Published: November 2017

AbstractPaclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2′ position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
Impacts of hemispheric solar geoengineering on tropical cyclone frequency
Authors: Jones Anthony C. , Haywood James M. , Dunstone Nick , Emanuel Kerry , Hawcroft Matthew K. , Hodges Kevin I. , Jones Andy 
Published: November 2017

AbstractSolar geoengineering refers to a range of proposed methods for counteracting global warming by artificially reducing sunlight at Earth’s surface. The most widely known solar geoengineering proposal is stratospheric aerosol injection (SAI), which has impacts analogous to those from volcanic eruptions. Observations following major volcanic eruptions indicate that aerosol enhancements confined to a single hemisphere effectively modulate North Atlantic tropical cyclone (TC) activity in the following years. Here we investigate the effects of both single-hemisphere and global SAI scenarios on North Atlantic TC activity using the HadGEM2-ES general circulation model and various TC identification methods. We show that a robust result from all of the methods is that SAI applied to the southern hemisphere would enhance TC frequency relative to a global SAI application, and vice versa for SAI in the northern hemisphere. Our results reemphasise concerns regarding regional geoengineering and should motivate policymakers to regulate large-scale unilateral geoengineering deployments.
AIP limits neurotransmitter release by inhibiting calcium bursts from the ryanodine receptor
Authors: Chen Bojun , Liu Ping , Hujber Edward J. , Li Yan , Jorgensen Erik M. , Wang Zhao-Wen 
Published: November 2017

AbstractPituitary tumors are frequently associated with mutations in the AIP gene and are sometimes associated with hypersecretion of growth hormone. It is unclear whether other factors besides an enlarged pituitary contribute to the hypersecretion. In a genetic screen for suppressors of reduced neurotransmitter release, we identified a mutation in Caenorhabditis elegans AIPR-1 (AIP-related-1), which causes profound increases in evoked and spontaneous neurotransmitter release, a high frequency of spontaneous calcium transients in motor neurons and an enlarged readily releasable pool of vesicles. Calcium bursts and hypersecretion are reversed by mutations in the ryanodine receptor but not in the voltage-gated calcium channel, indicating that these phenotypes are caused by a leaky ryanodine receptor. AIPR-1 is physically associated with the ryanodine receptor at synapses. Finally, the phenotypes in aipr-1 mutants can be rescued by presynaptic expression of mouse AIP, demonstrating that a conserved function of AIP proteins is to inhibit calcium release from ryanodine receptors.
Integrated radiomic framework for breast cancer and tumor biology using advanced machine learning and multiparametric MRI
Authors: Parekh Vishwa S. , Jacobs Michael A. 
Published: November 2017

AbstractRadiomics deals with the high throughput extraction of quantitative textural information from radiological images that not visually perceivable by radiologists. However, the biological correlation between radiomic features and different tissues of interest has not been established. To that end, we present the radiomic feature mapping framework to generate radiomic MRI texture image representations called the radiomic feature maps (RFM) and correlate the RFMs with quantitative texture values, breast tissue biology using quantitative MRI and classify benign from malignant tumors. We tested our radiomic feature mapping framework on a retrospective cohort of 124 patients (26 benign and 98 malignant) who underwent multiparametric breast MR imaging at 3 T. The MRI parameters used were T1-weighted imaging, T2-weighted imaging, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI). The RFMs were computed by convolving MRI images with statistical filters based on first order statistics and gray level co-occurrence matrix features. Malignant lesions demonstrated significantly higher entropy on both post contrast DCE-MRI (Benign-DCE entropy: 5.72 ± 0.12, Malignant-DCE entropy: 6.29 ± 0.06, p = 0.0002) and apparent diffusion coefficient (ADC) maps as compared to benign lesions (Benign-ADC entropy: 5.65 ± 0.15, Malignant ADC entropy: 6.20 ± 0.07, p = 0.002). There was no significant difference between glandular tissue entropy values in the two groups. Furthermore, the RFMs from DCE-MRI and DWI demonstrated significantly different RFM curves for benign and malignant lesions indicating their correlation to tumor vascular and cellular heterogeneity respectively. There were significant differences in the quantitative MRI metrics of ADC and perfusion. The multiview IsoSVM model classified benign and malignant breast tumors with sensitivity and specificity of 93 and 85%, respectively, with an AUC of 0.91.
A bacterial pioneer produces cellulase complexes that persist through community succession
Authors: Kolinko Sebastian , Wu Yu-Wei , Tachea Firehiwot , Denzel Evelyn , Hiras Jennifer , Gabriel Raphael , Bäcker Nora , Chan Leanne Jade G. , Eichorst Stephanie A. , Frey Dario , Chen Qiushi , Azadi Parastoo , Adams Paul D. , Pray Todd R. , Tanjore Deepti , Petzold Christopher J. , Gladden John M. , Simmons Blake A. , Singer Steven W. 
Published: November 2017

AbstractCultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, ‘Candidatus Reconcilibacillus cellulovorans’, possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the ‘Ca. Reconcilibacillus cellulovorans’ multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures for enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. The provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.
Supernatural Belief Is Not Modulated by Intuitive Thinking Style or Cognitive Inhibition
Authors: Farias Miguel , van Mulukom Valerie , Kahane Guy , Kreplin Ute , Joyce Anna , Soares Pedro , Oviedo Lluis , Hernu Mathilde , Rokita Karolina , Savulescu Julian , Möttönen Riikka 
Published: November 2017

AbstractAccording to the Intuitive Belief Hypothesis, supernatural belief relies heavily on intuitive thinking—and decreases when analytic thinking is engaged. After pointing out various limitations in prior attempts to support this Intuitive Belief Hypothesis, we test it across three new studies using a variety of paradigms, ranging from a pilgrimage field study to a neurostimulation experiment. In all three studies, we found no relationship between intuitive or analytical thinking and supernatural belief. We conclude that it is premature to explain belief in gods as ‘intuitive’, and that other factors, such as socio-cultural upbringing, are likely to play a greater role in the emergence and maintenance of supernatural belief than cognitive style.