bluuebunny/crossref_metadata_2025_split huggingface dataset:
VP214 Criteria That Influence The Brazilian Public Decision-Making
Authors: de Souza Andrea Brígida , Santos Marisa 
Published: January 2018

INTRODUCTION:In Brazil, the National Committee for Health Technology Incorporation in the public health system (CONITEC) advises the Ministry of Health about incorporation, exclusion and alteration of health technologies in Brazilian public health system (SUS). Decision making considers multiple criteria, included or not in legislation. This analysis was the first step for a multiple-criteria decision analysis (MCDA) building. This study aims to identify criteria that influence Health Technology Assessment (HTA) for SUS.METHODS:Five real cases of controversial recommendations of technology incorporation made by CONITEC were reviewed by listening to the plenary recordings and reviewing committee minutes. The choice was guided by convenience, with prioritization according to CONITEC's members, using a pre-defined standardized form. Weight in decision making was also raised and identified. Selected technologies judgments were: Trastuzumab for metastatic/advanced Breast Cancer; Fingolimod for Multiple Sclerosis; Clozapine, Lamotrigine, Olanzapine, Quetiapine and Risperidone for Bipolar Affective Disorder; Hematopoietic stem cell transplantation for Sickle Cell Disease; and Positron Emission Computed Tomography (PET-CT) for Lung Cancer and for hepatic metastasis from Colorectal Cancer.RESULTS:The choice of different technologies allowed verifying specific criteria used for the incorporation of each type of technology, as well as the similar criteria discussed and used by all these technology types. In addition, some identified criteria were specific to the Brazilian reality, such as: “Incorporation by other countries”, “Potential technologies without registration in Brazil” and “Off-label use”. These criteria were not previously identified in studies conducted in other countries. Some criteria have been identified in all decisions, such as: efficacy, disease severity, quality and confidence in the evidences, logistic challenges for implementation, unmet needs, budget impact and treatment costs. Relative impact of cost-effectiveness was considered low.CONCLUSIONS:CONITEC's recordings are an important source to understand the Brazilian decision-making process. To identify the important criteria can help to standardize and improve the HTA process.
Results of balloon pulmonary valvoplasty in children with Noonan’s syndrome
Authors: Holzmann Jonathon , Tibby Shane M. , Rosenthal Eric , Qureshi Shakeel , Morgan Gareth , Krasemann Thomas 
Published: January 2018

AbstractPulmonary valve stenosis is common in patients with Noonan’s syndrome. The response to balloon valvoplasty varies.We assessed the correlation between re-intervention rate, immediate response, and the progress of the valve gradient over time after intervention.MethodsThis is a retrospective study conducted from 1995 to 2014.ResultsOf 14 patients identified, seven had re-intervention 28±54 months (range 3–149, median 3.3) after valvoplasty. These patients did not have a significant decrease in gradient after intervention. Their gradient subsequently decreased during follow-up and then became static before increasing years after intervention. In contrast, the gradient of patients not requiring further intervention continually reduced over time. Demographics did not differ between these groups.ConclusionWe could not identify predisposing factors for long-term success of pulmonary valvoplasty in Noonan’s patients, but the trajectory of gradients differs significantly between patients needing re-intervention from those who remain free from re-intervention.
Direct characterization of a nonlinear photonic circuit’s wave function with laser light
Authors: Lenzini Francesco , Poddubny Alexander N , Titchener James , Fisher Paul , Boes Andreas , Kasture Sachin , Haylock Ben , Villa Matteo , Mitchell Arnan , Solntsev Alexander S , Sukhorukov Andrey A , Lobino Mirko 
Published: January 2018

AbstractIntegrated photonics is a leading platform for quantum technologies including nonclassical state generation1, 2, 3, 4, demonstration of quantum computational complexity5 and secure quantum communications6. As photonic circuits grow in complexity, full quantum tomography becomes impractical, and therefore an efficient method for their characterization7, 8 is essential. Here we propose and demonstrate a fast, reliable method for reconstructing the two-photon state produced by an arbitrary quadratically nonlinear optical circuit. By establishing a rigorous correspondence between the generated quantum state and classical sum-frequency generation measurements from laser light, we overcome the limitations of previous approaches for lossy multi-mode devices9, 10. We applied this protocol to a multi-channel nonlinear waveguide network and measured a 99.28±0.31% fidelity between classical and quantum characterization. This technique enables fast and precise evaluation of nonlinear quantum photonic networks, a crucial step towards complex, large-scale, device production.
Phosphate insensitive aminophosphonate mineralisation within oceanic nutrient cycles
Authors: Chin Jason P , Quinn John P , McGrath John W 
Published: January 2018

Abstract
Many areas of the ocean are nutrient-poor yet support large microbial populations, leading to intense competition for and recycling of nutrients. Organic phosphonates are frequently found in marine waters, but require specialist enzymes for catabolism. Previous studies have shown that the genes that encode these enzymes in marine systems are under Pho regulon control and so are repressed by inorganic phosphate. This has led to the conclusion that phosphonates are recalcitrant in much of the ocean, where phosphorus is not limiting despite the degradative genes being common throughout the marine environment. Here we challenge this paradigm and show, for the first time, that bacteria isolated from marine samples have the ability to mineralise 2-aminoethylphosphonate, the most common biogenic marine aminophosphonate, via substrate-inducible gene regulation rather than via Pho-regulated metabolism. Substrate-inducible, Pho-independent 2-aminoethylphosphonate catabolism therefore represents a previously unrecognised component of the oceanic carbon, nitrogen and phosphorus cycles.
Corallivory and the microbial debacle in two branching scleractinians
Authors: Bettarel Yvan , Halary Sébastien , Auguet Jean-Christophe , Mai Thanh Chi , Van Bui Ngoc , Bouvier Thierry , Got Patrice , Bouvier Corinne , Monteil-Bouchard Sonia , Christelle Desnues 
Published: January 2018

Abstract
The grazing activity by specific marine organisms represents a growing threat to the survival of many scleractinian species. For example, the recent proliferation of the corallivorous gastropod Drupella now constitutes a critical case in all South-East Asian waters. If the damaging effects caused by this marine snail on coral polyps are relatively well known, the indirect incidence of predation on coral microbial associates is still obscure and might also potentially impair coral health. In this study, we compared the main ecological traits of coral-associated bacterial and viral communities living in the mucus layer of Acropora formosa and Acropora millepora, of healthy and predated individuals (i.e., colonized by Drupella rugosa), in the Bay of Van Phong (Vietnam). Our results show a substantial impact of the gastropod on a variety of microbiological markers. Colonized corals harbored much more abundant and active epibiotic bacteria whose community composition shifted toward more pathogenic taxa (belonging to the Vibrionales, Clostridiales, Campylobacterales, and Alteromonadales orders), together with their specific phages. Viral epibionts were also greatly influenced by Drupella corallivory with spectacular modifications in their concentrations, life strategies, genotype richness, and diversity. Novel and abundant circular Rep-encoding ssDNA viruses (CRESS-DNA viruses) were detected and characterized in grazed corals and we propose that their occurrence may serve as indicator of the coral health status. Finally, our results reveal that corallivory can cause severe dysbiosis by altering virus–bacteria interactions in the mucus layer, and ultimately favoring the development of local opportunistic infections.
Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function
Authors: Miao Yifei , Ajami Nassim E. , Huang Tse-Shun , Lin Feng-Mao , Lou Chih-Hong , Wang Yun-Ting , Li Shuai , Kang Jian , Munkacsi Hannah , Maurya Mano R. , Gupta Shakti , Chien Shu , Subramaniam Shankar , Chen Zhen 
Published: January 2018

AbstractThe optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.
Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development
Authors: Krishnan Navasona , Bonham Christopher A. , Rus Ioana A. , Shrestha Om Kumar , Gauss Carla M. , Haque Aftabul , Tocilj Ante , Joshua-Tor Leemor , Tonks Nicholas K. 
Published: January 2018

AbstractThe protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.
Order enables efficient electron-hole separation at an organic heterojunction with a small energy loss
Authors: Menke S. Matthew , Cheminal Alexandre , Conaghan Patrick , Ran Niva A. , Greehnam Neil C. , Bazan Guillermo C. , Nguyen Thuc-Quyen , Rao Akshay , Friend Richard H. 
Published: January 2018

AbstractDonor–acceptor organic solar cells often show low open-circuit voltages (VOC) relative to their optical energy gap (Eg) that limit power conversion efficiencies to ~12%. This energy loss is partly attributed to the offset between Eg and that of intermolecular charge transfer (CT) states at the donor–acceptor interface. Here we study charge generation occurring in PIPCP:PC61BM, a system with a very low driving energy for initial charge separation (Eg−ECT ~ 50 meV) and a high internal quantum efficiency (ηIQE ~ 80%). We track the strength of the electric field generated between the separating electron-hole pair by following the transient electroabsorption optical response, and find that while localised CT states are formed rapidly (<100 fs) after photoexcitation, free charges are not generated until 5 ps after photogeneration. In PIPCP:PC61BM, electronic disorder is low (Urbach energy <27 meV) and we consider that free charge separation is able to outcompete trap-assisted non-radiative recombination of the CT state.
Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles
Authors: Wentzel Corinna , Delvendahl Igor , Sydlik Sebastian , Georgiev Oleg , Müller Martin 
Published: January 2018

AbstractHere we explore the relationship between presynaptic homeostatic plasticity and proteasome function at the Drosophila neuromuscular junction. First, we demonstrate that the induction of homeostatic plasticity is blocked after presynaptic proteasome perturbation. Proteasome inhibition potentiates release under baseline conditions but not during homeostatic plasticity, suggesting that proteasomal degradation and homeostatic plasticity modulate a common pool of vesicles. The vesicles that are regulated by proteasome function and recruited during homeostatic plasticity are highly EGTA sensitive, implying looser Ca2+ influx-release coupling. Similar to homeostatic plasticity, proteasome perturbation enhances presynaptic Ca2+ influx, readily-releasable vesicle pool size, and does not potentiate release after loss of specific homeostatic plasticity genes, including the schizophrenia-susceptibility gene dysbindin. Finally, we provide genetic evidence that Dysbindin levels regulate the access to EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein degradation opposes the release of low-release probability vesicles that are potentiated during homeostatic plasticity and whose access is controlled by dysbindin.
Quantitative optical nanophysiology of Ca2+ signaling at inner hair cell active zones
Authors: Neef Jakob , Urban Nicolai T. , Ohn Tzu-Lun , Frank Thomas , Jean Philippe , Hell Stefan W. , Willig Katrin I. , Moser Tobias 
Published: January 2018

AbstractCa2+ influx triggers the release of synaptic vesicles at the presynaptic active zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is critical for understanding synaptic transmission. However, this has remained challenging to establish at the required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy to quantify the number (20–330) and arrangement (mostly linear 70 nm × 100–600 nm clusters) of Ca2+ channels at AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we analyze presynaptic Ca2+ signals at the nanometer scale and find confined elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence lifetime analysis, we arrive at estimates of the Ca2+ concentrations at stimulated IHC AZs of on average 25 µM. We propose that IHCs form bassoon-dependent presynaptic Ca2+-channel clusters of similar density but scalable length, thereby varying the number of Ca2+ channels amongst individual AZs.
Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast
Authors: Lee Soyun , Oh Seunghee , Jeong Kwiwan , Jo Hyelim , Choi Yoonjung , Seo Hogyu David , Kim Minhoo , Choe Joonho , Kwon Chang Seob , Lee Daeyoup 
Published: January 2018

AbstractDot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and does not methylate free histones and thus may have different actions with respect to other histone methyltransferases. Here we show that Dot1p displays histone chaperone activity and regulates nucleosome dynamics via histone exchange in yeast. We show that a methylation-independent function of Dot1p is required for the cryptic transcription within transcribed regions seen following disruption of the Set2–Rpd3S pathway. Dot1p can assemble core histones to nucleosomes and facilitate ATP-dependent chromatin-remodeling activity through its nucleosome-binding domain, in vitro. Global analysis indicates that Dot1p appears to be particularly important for histone exchange and chromatin accessibility on the transcribed regions of long-length genes. Our findings collectively suggest that Dot1p-mediated histone chaperone activity controls nucleosome dynamics in transcribed regions.
Cigarette smoking is associated with an altered vaginal tract metabolomic profile
Authors: Nelson T. M. , Borgogna J. C. , Michalek R. D. , Roberts D. W. , Rath J. M. , Glover E. D. , Ravel J. , Shardell M. D. , Yeoman C. J. , Brotman R. M. 
Published: January 2018

AbstractCigarette smoking has been associated with both the diagnosis of bacterial vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As the mechanism linking smoking with vaginal microbiota and BV is unclear, we sought to compare the vaginal metabolomes of smokers and non-smokers (17 smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S rRNA gene populations revealed samples clustered into three community state types (CSTs) ---- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST-IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the breakdown metabolites cotinine and hydroxycotinine were substantially higher in smokers, as expected. Among women categorized to CST-IV, biogenic amines, including agmatine, cadaverine, putrescine, tryptamine and tyramine were substantially higher in smokers, while dipeptides were lower in smokers. These biogenic amines are known to affect the virulence of infective pathogens and contribute to vaginal malodor. Our data suggest that cigarette smoking is associated with differences in important vaginal metabolites, and women who smoke, and particularly women who are also depauperate for Lactobacillus spp., may have increased susceptibilities to urogenital infections and increased malodor.
Directional sound beam emission from a configurable compact multi-source system
Authors: Zhao Jiajun , Jahdali Rasha Al , Zhang Likun , Wu Ying 
Published: January 2018

AbstractWe propose to achieve efficient emission of highly directional sound beams from multiple monopole sources embedded in a subwavelength enclosure. Without the enclosure, the emitted sound fields have an indistinguishable or omnidirectional radiation directivity in far fields. The strong directivity formed in the presence of the enclosure is attributed to interference of sources under degenerate Mie resonances in the enclosure of anisotropic property. Our numerical simulations of sound emission from the sources demonstrate the radiation of a highly directed sound beam of unidirectional or bidirectional patterns, depending on how the sources are configured inside the enclosure. Our scheme, if achieved, can solve the challenging problem of poor directivity of a subwavelength sound system, and can guide beam forming and collimation by miniaturized devices.
Genomic and transcriptomic analysis of the Asian honeybee Apis cerana provides novel insights into honeybee biology
Authors: Diao Qingyun , Sun Liangxian , Zheng Huajun , Zeng Zhijiang , Wang Shengyue , Xu Shufa , Zheng Huoqing , Chen Yanping , Shi Yuanyuan , Wang Yuezhu , Meng Fei , Sang Qingliang , Cao Lianfei , Liu Fang , Zhu Yongqiang , Li Wenfeng , Li Zhiguo , Dai Congjie , Yang Minjun , Chen Shenglu , Chen Runsheng , Zhang Shaowu , Evans Jay D. , Huang Qiang , Liu Jie , Hu Fuliang , Su Songkun , Wu Jie 
Published: January 2018

AbstractThe Asian honeybee Apis cerana is one of two bee species that have been commercially kept with immense economic value. Here we present the analysis of genomic sequence and transcriptomic exploration for A. cerana as well as the comparative genomic analysis of the Asian honeybee and the European honeybee A. mellifera. The genome and RNA-seq data yield new insights into the behavioral and physiological resistance to the parasitic mite Varroa the evolution of antimicrobial peptides, and the genetic basis for labor division in A. cerana. Comparison of genes between the two sister species revealed genes specific to A. cerana, 54.5% of which have no homology to any known proteins. The observation that A. cerana displayed significantly more vigilant grooming behaviors to the presence of Varroa than A. mellifera in conjunction with gene expression analysis suggests that parasite-defensive grooming in A. cerana is likely triggered not only by exogenous stimuli through visual and olfactory detection of the parasite, but also by genetically endogenous processes that periodically activates a bout of grooming to remove the ectoparasite. This information provides a valuable platform to facilitate the traits unique to A. cerana as well as those shared with other social bees for health improvement.
Loss of disease tolerance during Citrobacter rodentium infection is associated with impaired epithelial differentiation and hyperactivation of T cell responses
Authors: Kang Eugene , Zhou Guangyan , Yousefi Mitra , Cayrol Romain , Xia Jianguo , Gruenheid Samantha 
Published: January 2018

AbstractCitrobacter rodentium is an intestinal mouse pathogen widely used as a model to study the mucosal response to infection. Inbred mouse strains suffer one of two fates following infection: self-limiting colitis or fatal diarrheal disease. We previously reported that Rspo2 is a major genetic determinant of the outcome of C. rodentium infection; Rspo2 induction during infection of susceptible mice leads to loss of intestinal function and mortality. Rspo2 induction does not impact bacterial colonization, but rather, impedes the ability of the host to tolerate C. rodentium infection. Here, we performed deep RNA sequencing and systematically analyzed the global gene expression profiles of C. rodentium-infected colon tissues from susceptible and resistant congenic mice strains to determine the common responses to infection and the Rspo2-mediated dysfunction pathway signatures associated with loss of disease tolerance. Our results highlight changes in metabolism, tissue remodeling, and host defence as common responses to infection. Conversely, increased Wnt and stem cell signatures, loss of epithelial differentiation, and exaggerated CD4+ T cell activation through increased antigen processing and presentation were specifically associated with the response to infection in susceptible mice. These data provide insights into the molecular mechanisms underlying intestinal dysfunction and disease tolerance during C. rodentium infection.