bluuebunny/crossref_metadata_2025 huggingface dataset:
Avian Health across the Landscape: Nestling Immunity Covaries with Changing Landcover
Authors: Merrill L , Stewart Merrill T E , Barger A M , Benson T J
Published: May 2019

The landscape composition of an organism’s home range or territory should influence aspects of its condition, including measures of immune function. Changes in immunocompetence arising from variation in landcover may provide important links between habitat changes and patterns of disease spread. To establish a baseline understanding for whether immune measures covary with changes in landcover, we examined associations between immunological parameters and landcover composition for adults and nestlings of five shrubland bird species. Specifically, we examined the bacteria-killing ability (BKA) of the blood plasma and profiles of the five avian leukocytes as our measures of immune function, and assessed the proportion of area around each bird’s nest that was composed of the four major landcover types in the Midwestern USA: row crop agriculture, developed, forest, and grass/shrub. We performed landcover assessments at 100 and 1000 m radius buffers to identify whether associations between habitat and immune function differed at the two spatial scales. As part of this work, we examined age and species-related immunological variation, as well as associations among the immune parameters. There was little evidence linking variation in immune function to landcover composition for the adults at either spatial scale, but there were numerous associations for nestlings, and these were stronger at the 1000 than 100 m spatial scale. The proportion of grass/shrub around the nest had the largest impact on immune function, although the effect varied by immune parameter and species. BKA and basophils were inversely associated with grass/shrub for all species, whereas lymphocytes were positively associated with grass/shrub for all species. We also documented species-level differences among adults and nestlings for BKA and all leukocytes except monocytes. As expected, we found that nestlings had reduced levels of BKA, lymphocytes, monocytes, and elevated heterophils compared with adults (except for field sparrow-Spizella pusilla-nestlings, which had higher lymphocytes). Basophils generally did not differ by age class, and eosinophils exhibited species-specific patterns, in which they were higher for nestling American robins (Turdus migratorius) and gray catbirds (Dumetella carolinensis) compared with adults, but lower in the other nestlings. Heterophils and lymphocytes were inversely associated for all species and age classes, and basophil levels were positively associated with BKA across species and age classes. Together, these findings bolster our understanding of age and species-specific variation in immune function, and provide evidence that immune measures can covary with changes in landcover.
Evolution of Insect Iridescence: Origins of Three-Dimensional Photonic Crystals in Weevils (Coleoptera: Curculionoidea)
Authors: Seago Ainsley E , Oberprieler Rolf , Saranathan Vinod Kumar
Published: May 2019

A variety of photonic mechanisms give rise to iridescence and other structural colors in insects. In weevils (Coleoptera: Curculionoidea), iridescence is created by the most complex of these mechanisms, the three-dimensional photonic crystal. These self-assembling crystals take the form of triply periodic networks with single diamond or single gyroid symmetries and have been the subject of many descriptive studies based on individual species (often on a single specimen). To determine how these extraordinary nanostructures have evolved, we conduct the first comparative study of photonic crystals and setal nanostructure across Curculionoidea. By integrating structural data with newly available phylogenetic information, we demonstrate that—despite their widespread geographical and taxonomic distribution—three-dimensional photonic crystals appear to have evolved only once in weevils, in the common ancestor of a clade comprising the current subfamilies Entiminae and Cyclominae. Flattened, hollow setae with an unordered, spongy network in the lumen appear to be a necessary precursor to three-dimensional photonic crystals; we propose an evolutionary pathway by which this transformation has occurred.
Elliptic Fibrations and the Hilbert Property
Authors: Demeio Julian Lawrence
Published: May 2019

For a number field $K$, an algebraic variety $X/K$ is said to have the Hilbert Property if $X(K)$ is not thin. We are going to describe some examples of algebraic varieties, for which the Hilbert Property is a new result. The first class of examples is that of smooth cubic hypersurfaces with a $K$-rational point in ${\mathbb{P}}_n/K$, for $n \geq 3$. These fall in the class of unirational varieties, for which the Hilbert Property was conjectured by Colliot-Thélène and Sansuc. We then provide a sufficient condition for which a surface endowed with multiple elliptic fibrations has the Hilbert Property. As an application, we prove the Hilbert Property of a class of K3 surfaces, and some Kummer surfaces.
Asymptotically Optimal Multi-Paving
Authors: Ravichandran Mohan , Srivastava Nikhil
Published: May 2019

Anderson’s paving conjecture, now known to be true [14], asserts that every zero-diagonal matrix admits a nontrivial paving with dimension independent bounds. We study this problem for a collection of matrices and show that given $k$ zero-diagonal $n\times n$ Hermitian matrices $A_1,\ldots ,A_k$ and $\epsilon>0$ there are diagonal projections $P_1,\ldots ,P_r$ with $\sum _{j\le r} P_j=I$ such that $||P_{j}A_iP_{j}||\le \epsilon ||A_i||$ for $i\le k, j\le r$, that is, a simultaneous paving of the matrices, with $r\le 18k/\epsilon ^2$. As a consequence, we get the optimal asymptotic estimates for paving a single zero-diagonal (not necessarily Hermitian) matrix: every square zero-diagonal complex matrix can be $\epsilon -$paved using $O(\epsilon ^{-2})$ blocks, improving the previously known bound of $O(\epsilon ^{-8})$. We use our result to strengthen a result of Johnson–Ozawa–Schechtman on commutator representations of zero trace matrices.
Potentiation of β-lactam antibiotics and β-lactam/β-lactamase inhibitor combinations against MDR and XDR Pseudomonas aeruginosa using non-ribosomal tobramycin–cyclam conjugates
Authors: Idowu Temilolu , Ammeter Derek , Arthur Gilbert , Zhanel George G , Schweizer Frank
Published: May 2019

Objectives

To develop a multifunctional adjuvant molecule that can rescue β-lactam antibiotics and β-lactam/β-lactamase inhibitor combinations from resistance in carbapenem-resistant Pseudomonas aeruginosa clinical isolates.

Methods

Preparation of adjuvant was guided by structure–activity relationships, following standard protocols. Susceptibility and chequerboard studies were assessed using serial 2-fold dilution assays. Toxicity was evaluated against porcine erythrocytes, human embryonic kidney (HEK293) cells and liver carcinoma (HepG2) cells via MTS assay. Preliminary in vivo efficacy was evaluated using a Galleria mellonella infection model.

Results

Conjugation of tobramycin and cyclam abrogates the ribosomal effects of tobramycin but confers a potent adjuvant property that restores full antibiotic activity of meropenem and aztreonam against carbapenem-resistant P. aeruginosa. Therapeutic levels of susceptibility, as determined by CLSI susceptibility breakpoints, were attained in several MDR clinical isolates, and time–kill assays revealed a synergistic dose-dependent pharmacodynamic relationship. A triple combination of the adjuvant with ceftazidime/avibactam (approved), aztreonam/avibactam (Phase III) and meropenem/avibactam enhances the efficacies of β-lactam/β-lactamase inhibitors against recalcitrant strains, suggesting rapid access of the combination to their periplasmic targets. The newly developed adjuvants, and their combinations, were non-haemolytic and non-cytotoxic, and preliminary in vivo evaluation in G. mellonella suggests therapeutic potential for the double and triple combinations.

Conclusions

Non-ribosomal tobramycin–cyclam conjugate mitigates the effect of OprD/OprF porin loss in P. aeruginosa and potentiates β-lactam/β-lactamase inhibitors against carbapenem-resistant clinical isolates, highlighting the complexity of resistance to β-lactam antibiotics. Our strategy presents an avenue to further preserve the therapeutic utility of β-lactam antibiotics.
Evaluation of interventions to improve inpatient hospital documentation within electronic health records: a systematic review
Authors: Wiebe Natalie , Otero Varela Lucia , Niven Daniel J , Ronksley Paul E , Iragorri Nicolas , Quan Hude
Published: May 2019

Objective

Despite the widespread and increasing use of electronic health records (EHRs), the quality of EHRs is problematic. Efforts have been made to address reasons for poor EHR documentation quality. Previous systematic reviews have assessed intervention effectiveness within the outpatient setting or paper documentation. The purpose of this systematic review was to assess the effectiveness of interventions seeking to improve EHR documentation within an inpatient setting.

Materials and Methods

A search strategy was developed based on elaborated inclusion/exclusion criteria. Four databases, gray literature, and reference lists were searched. A REDCap data capture form was used for data extraction, and study quality was assessed using a customized tool. Data were analyzed and synthesized in a narrative, semiquantitative manner.

Results

Twenty-four studies were included in this systematic review. Owing to high heterogeneity, quantitative comparison was not possible. However, statistically significant results in interventions and affected outcomes were analyzed and discussed. Education and implementation of a new EHR reporting system were the most successful interventions, as evidenced by significantly improved EHR documentation.

Discussion

Heterogeneity of interventions, outcomes, document type, EHR user, and other variables led to difficulty in measuring EHR documentation quality and effectiveness of interventions. However, the use of education as a primary intervention aligned closely with existing literature in similar fields.

Conclusions

Interventions implemented to enhance EHR documentation are highly variable and require standardization. Emphasis should be placed on this novel area of research to improve communication between healthcare providers and facilitate data sharing between centers and countries.

PROSPERO Registration Number: CRD42017083494.
Impact of weaning age on rumen development in artificially reared lambs1
Authors: Carballo Omar Cristobal , Khan Muhammad Ajmal , Knol Frederik Willem , Lewis Sarah Jeanne , Stevens David Robert , Laven Richard Anthony , McCoard Susan Anne
Published: May 2019

ABSTRACT: This study examined the impact of weaning age (4 vs. 6 wk) on rumen morphological and metabolic development in artificially reared lambs. Thirty-two mixed-sex lambs (2 to 5 d old) were randomly allocated to 1 of 2 weaning groups: early weaning (EW; 4 wk) and control (Ctrl; 6 wk). Lambs were individually penned and fed milk replacer (MR; 24% CP and 25% fat, DM basis) at 20% of their corresponding initial BW. Weaning was achieved by gradual reduction of MR allowance over a period of 3 wk using a step-down procedure. Concentrate and meadow hay were offered ad libitum from 1 d of the study until 6 wk, when lambs were transferred to a mixed sward pasture. At week 4, individual DMI were recorded and blood samples collected to measure β-hydroxybutyrate (BHBA) and NEFA. Eight animals per group were euthanized at week 4 and 16 to evaluate short chain fatty acids (SCFA) and histomorphometry of the rumen walls: dorsal (DS), ventral (VS), dorsal blind (DBS), and ventral blind (VBS) sacs. Linear mixed models were used to analyze the effect of weaning treatments at week 4 and 16, and to compare between timepoints and between rumen sites. Dry matter intake and rumen SCFA profiles were similar between groups (P > 0.10) at week 4 and 16. Plasma concentrations of BHBA were greater (P = 0.03) in EW than in Ctrl lambs, while NEFA did not differ (P > 0.10) between groups at week 4. No effect of weaning age on rumen empty weight, and papillae density, length, width, surface area ratio, and muscle layer thickness at any of the 4 rumen sites was found (P > 0.10) at either week 4 or week 16, except for greater (P = 0.02) papillae epithelium thickness in the DBS at week 4 in EW than Ctrl lambs. Papillae morphology and muscular thickness differed across rumen sites at week 4 and week 16 (P < 0.05), except for papillae density and surface area ratio at 4 week (P > 0.10). Rumen papillae length, width, and muscle layer thickness increased while papillae density and surface area ratio decreased (P < 0.05) between 4 and 16 wk. The results of this study indicate that morphological and physiological development of the rumen can be accelerated to support weaning of artificially reared lambs at 4 wk, using a step-down weaning system. Morphological differences between rumen sacs denote that future studies in lambs evaluating the impact of different diets should involve representative sampling across the rumen rather than a single site to more accurately study rumen development and ontogenic changes.
State Contingent Debt as Insurance for Euro Area Sovereigns
Authors: Demertzis Maria , Zenios Stavros A
Published: May 2019

The authors provide a novel angle to the ongoing discussions by the G20 on sovereign contingent debt and argue that contingent debt could provide market-based insurance to protect the euro area from future debt crises. Risk-sharing with the markets is a practical way forward in the context of the Franco-German debate on risk-sharing among EU member states vs system-wide risk reduction. The financial innovation of contingent debt is a feasible euro area reform that would not introduce risk-sharing between states or require institutional reforms or Treaty changes. However, coordination would be needed. The authors’ suggestion fills a gap in the proposals on the completion of the banking union and the possible establishment of a European Monetary Fund (EMF). These proposals offer institutions-based solutions to crises, with the banking union providing safety regulations that will make banking institutions more resilient, while the EMF will be a ‘fire brigade’ to be called on in emergencies. What has not been tapped are the markets, whose tolerant behaviour to sovereign demands encouraged the build up of debt, while their finicky response exacerbated the crisis.
Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma
Authors: Rohde Christoph , Yamaguchi Rin , Mukhina Svetlana , Sahin Ugur , Itoh Kyogo , Türeci Özlem
Published: May 2019

CLDN18.2 expression is highly prevalent in Japanese patients with gastric cancer, making it a targetable alteration, and supporting development of zolbetuximab as a therapeutic agent for this patient population.
Variation in Tense and Aspect, and the Temporal Interpretation of Complement Clauses
Authors: Bochnak M Ryan , Hohaus Vera , Mucha Anne
Published: May 2019

In this paper, we investigate the temporal interpretation of propositional attitude complement clauses in four typologically unrelated languages: Washo (language isolate), Medumba (Niger-Congo), Hausa (Afro-Asiatic), and Samoan (Austronesian). Of these languages, Washo and Medumba are optional-tense languages, while Hausa and Samoan are tenseless. Just like in obligatory-tense languages, we observe variation among these languages when it comes to the availability of so-called simultaneous and backward-shifted readings of complement clauses. For our optional-tense languages, we argue that a Sequence of Tense parameter is active in these languages, just as in obligatory-tense languages. However, for completely tenseless clauses, we need something more. We argue that there is variation in the degree to which languages make recourse to res-movement, or a similar mechanism that manipulates LF structures to derive backward-shifted readings in tenseless complement clauses. We additionally appeal to cross-linguistic variation in the lexical semantics of perfective aspect to derive or block certain readings. The result is that the typological classification of a language as tensed, optionally tensed, or tenseless, does not alone determine the temporal interpretation possibilities for complement clauses. Rather, structural parameters of variation cross-cut these broad classes of languages to deliver the observed cross-linguistic picture.
Changes in productivity and carbon storage of grasslands in China under future global warming scenarios of 1.5°C and 2°C
Authors: Wang Zhaoqi , Chang Jinfeng , Peng Shushi , Piao Shilong , Ciais Philippe , Betts Richard
Published: May 2019

Aims

The impacts of future global warming of 1.5°C and 2°C on the productivity and carbon (C) storage of grasslands in China are not clear yet, although grasslands in China support ~45 million agricultural populations and more than 238 million livestock populations, and are sensitive to global warming.

Methods

This study used a process-based terrestrial ecosystem model named ORCHIDEE to simulate C cycle of alpine meadows and temperate grasslands in China. This model was driven by high-resolution (0.5° × 0.5°) climate of global specific warming levels (SWL) of 1.5°C and 2°C (warmer than pre-industrial level), which is downscaled by EC-EARTH3-HR v3.1 with sea surface temperature and sea-ice concentration as boundary conditions from IPSL-CM5-LR (low spatial resolution, 2.5° × 1.5°) Earth system model (ESM).

Important Findings

Compared with baseline (1971–2005), the mean annual air temperature over Chinese grasslands increased by 2.5°C and 3.7°C under SWL1.5 and SWL2, respectively. The increase in temperature in the alpine meadow was higher than that in the temperate grassland under both SWL1.5 and SWL2. Precipitation was also shown an increasing trend under SWL2 over most of the Chinese grasslands. Strong increases in gross primary productivity (GPP) were simulated in the Chinese grasslands, and the mean annual GPP (GPPMA) increased by 19.32% and 43.62% under SWL1.5 and SWL2, respectively. The C storage increased by 0.64 Pg C and 1.37 Pg C under SWL1.5 and SWL2 for 50 years simulations. The GPPMA was 0.670.390.88 (0.82) (model meanminmax (this study)), 0.850.451.24 (0.97) and 0.940.611.30 (1.17) Pg C year−1 under baseline, SWL1.5 and SWL2 modeled by four CMIP5 ESMs (phase 5 of the Coupled Model Inter-comparison Project Earth System Models). In contrast, the mean annual net biome productivity was −18.55−40.374.47 (−3.61),18.65−2.0364.03 (10.29) and 24.158.3838.77 (24.93) Tg C year−1 under baseline, SWL1.5 and SWL2 modeled by the four CMIP5 ESMs. Our results indicated that the Chinese grasslands would have higher productivity than the baseline and can mitigate climate change through increased C sequestration under future global warming of 1.5°C and 2°C with the increase of precipitation and the global increase of atmospheric CO2 concentration.
The dipole of the galaxy bispectrum
Authors: Clarkson Chris , de Weerd Eline M , Jolicoeur Sheean , Maartens Roy , Umeh Obinna
Published: May 2019

The bispectrum will play an important role in future galaxy surveys. On large scales it is a key probe for measuring primordial non-Gaussianity which can help differentiate between different inflationary models and other theories of the early universe. On these scales a variety of relativistic effects come into play once the galaxy number-count fluctuation is projected on to our past light-cone. We show for the first time that the leading relativistic correction from these distortions in the galaxy bispectrum generates a significant dipole, mainly from relativistic redshift space distortions. The amplitude of the dipole can be more than 10 per cent of the monopole even on equality scales. Such a dipole is absent in the Newtonian approximation to the redshift space bispectrum, so it offers a clear signature of relativistic effects on cosmological scales in large-scale structure.
Potential roles of aquaporin 9 in the pathogenesis of endometriosis
Authors: Choi Young Sik , Park Ji Hyun , Yoon Jeong-Kee , Yoon Ji Sun , Kim Jung Sook , Lee Jae Hoon , Yun Bo Hyun , Park Joo Hyun , Seo Seok Kyo , Cho SiHyun , Lee Byung Seok , Taylor Hugh S
Published: May 2019

Aquaporins (AQPs) are involved in cell migration, proliferation and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis have not been fully evaluated. In this study, tissue samples were obtained from women undergoing laparoscopic surgery for endometriosis and other benign conditions. Analysis of expressions of AQP subtypes in eutopic and ectopic endometrium of patients with endometriosis (Eu-EMS and Ect-EMS, respectively) and eutopic endometrium of control patients without endometriosis (Eu-CTL) were performed using the NanoString nCounter System and western blotting. Human endometrial stromal cells (HESCs) were cultured and transfected with the siRNA of the AQP of interest. Among the AQP1–9 subtypes, endometrial expression of AQP2 and AQP8 was significantly increased, whereas AQP9 expression was significantly decreased in the Eu-EMS group compared to the Eu-CTL group. Comparison of expression of AQP2, AQP8 and AQP9 among Eu-EMS, Ect-EMS and Eu-CTL groups revealed significant differences for only AQP9. Expression of AQP9 in the Eu-EMS group was decreased compared with that in Eu-CTL. After transfection of AQP9 siRNA in HESCs, expressions of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 and phosphorylated p38 MAPK proteins after transfection was also confirmed using western blot analysis. Increased migration and invasion potentials of HESCs after transfection were determined by migration and wound healing assays. These findings suggest that AQP9 may be involved in the pathogenesis of endometriosis and warrant further investigation as a potential therapeutic target for treating endometriosis.
CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing
Authors: Labun Kornel , Montague Tessa G , Krause Maximilian , Torres Cleuren Yamila N , Tjeldnes Håkon , Valen Eivind
Published: May 2019

The CRISPR–Cas system is a powerful genome editing tool that functions in a diverse array of organisms and cell types. The technology was initially developed to induce targeted mutations in DNA, but CRISPR–Cas has now been adapted to target nucleic acids for a range of purposes. CHOPCHOP is a web tool for identifying CRISPR–Cas single guide RNA (sgRNA) targets. In this major update of CHOPCHOP, we expand our toolbox beyond knockouts. We introduce functionality for targeting RNA with Cas13, which includes support for alternative transcript isoforms and RNA accessibility predictions. We incorporate new DNA targeting modes, including CRISPR activation/repression, targeted enrichment of loci for long-read sequencing, and prediction of Cas9 repair outcomes. Finally, we expand our results page visualization to reveal alternative isoforms and downstream ATG sites, which will aid users in avoiding the expression of truncated proteins. The CHOPCHOP web tool now supports over 200 genomes and we have released a command-line script for running larger jobs and handling unsupported genomes. CHOPCHOP v3 can be found at https://chopchop.cbu.uib.no
LnCompare: gene set feature analysis for human long non-coding RNAs
Authors: Carlevaro-Fita Joana , Liu Leibo , Zhou Yuan , Zhang Shan , Chouvardas Panagiotis , Johnson Rory , Li Jianwei
Published: May 2019

Interest in the biological roles of long noncoding RNAs (lncRNAs) has resulted in growing numbers of studies that produce large sets of candidate genes, for example, differentially expressed between two conditions. For sets of protein-coding genes, ontology and pathway analyses are powerful tools for generating new insights from statistical enrichment of gene features. Here we present the LnCompare web server, an equivalent resource for studying the properties of lncRNA gene sets. The Gene Set Feature Comparison mode tests for enrichment amongst a panel of quantitative and categorical features, spanning gene structure, evolutionary conservation, expression, subcellular localization, repetitive sequences and disease association. Moreover, in Similar Gene Identification mode, users may identify other lncRNAs by similarity across a defined range of features. Comprehensive results may be downloaded in tabular and graphical formats, in addition to the entire feature resource. LnCompare will empower researchers to extract useful hypotheses and candidates from lncRNA gene sets.
HNADOCK: a nucleic acid docking server for modeling RNA/DNA–RNA/DNA 3D complex structures
Authors: He Jiahua , Wang Jun , Tao Huanyu , Xiao Yi , Huang Sheng-You
Published: May 2019

Interactions between nuclide acids (RNA/DNA) play important roles in many basic cellular activities like transcription regulation, RNA processing, and protein synthesis. Therefore, determining the complex structures between RNAs/DNAs is crucial to understand the molecular mechanism of related RNA/DNA–RNA/DNA interactions. Here, we have presented HNADOCK, a user-friendly web server for nucleic acid (NA)–nucleic acid docking to model the 3D complex structures between two RNAs/DNAs, where both sequence and structure inputs are accepted for RNAs, while only structure inputs are supported for DNAs. HNADOCK server was tested through both unbound structure and sequence inputs on the benchmark of 60 RNA–RNA complexes and compared with the state-of-the-art algorithm SimRNA. For structure input, HNADOCK server achieved a high success rate of 71.7% for top 10 predictions, compared to 58.3% for SimRNA. For sequence input, HNADOCK server also obtained a satisfactory performance and gave a success rate of 83.3% when the bound RNA templates are included or 53.3% when excluding those bound RNA templates. It was also found that inclusion of the inter-RNA base-pairing information from RNA–RNA interaction prediction can significantly improve the docking accuracy, especially for the top prediction. HNADOCK is fast and can normally finish a job in about 10 minutes. The HNADOCK web server is available at http://huanglab.phys.hust.edu.cn/hnadock/.
SEPPA 3.0—enhanced spatial epitope prediction enabling glycoprotein antigens
Authors: Zhou Chen , Chen Zikun , Zhang Lu , Yan Deyu , Mao Tiantian , Tang Kailin , Qiu Tianyi , Cao Zhiwei
Published: May 2019

B-cell epitope information is critical to immune therapy and vaccine design. Protein epitopes can be significantly affected by glycosylation, while no methods have considered this till now. Based on previous versions of Spatial Epitope Prediction of Protein Antigens (SEPPA), we here present an enhanced tool SEPPA 3.0, enabling glycoprotein antigens. Parameters were updated based on the latest and largest dataset. Then, additional micro-environmental features of glycosylation triangles and glycosylation-related amino acid indexes were added as important classifiers, coupled with final calibration based on neighboring antigenicity. Logistic regression model was retained as SEPPA 2.0. The AUC value of 0.794 was obtained through 10-fold cross-validation on internal validation. Independent testing on general protein antigens resulted in AUC of 0.740 with BA (balanced accuracy) of 0.657 as baseline of SEPPA 3.0. Most importantly, when tested on independent glycoprotein antigens only, SEPPA 3.0 gave an AUC of 0.749 and BA of 0.665, leading the top performance among peers. As the first server enabling accurate epitope prediction for glycoproteins, SEPPA 3.0 shows significant advantages over popular peers on both general protein and glycoprotein antigens. It can be accessed at http://bidd2.nus.edu.sg/SEPPA3/ or at http://www.badd-cao.net/seppa3/index.html. Batch query is supported.
MERMAID: dedicated web server to prepare and run coarse-grained membrane protein dynamics
Authors: Damre Mangesh , Marchetto Alessandro , Giorgetti Alejandro
Published: May 2019

Atomistic molecular dynamics simulations of membrane proteins have been shown to be extremely useful for characterizing the molecular features underlying their function, but require high computational power, limiting the understanding of complex events in membrane proteins, e.g. ion channels gating, GPCRs activation. To overcome this issue, it has been shown that coarse-grained approaches, although requiring less computational power, are still capable of correctly describing molecular events underlying big conformational changes in biological systems. Here, we present the Martini coarse-grained membrane protein dynamics (MERMAID), a publicly available web interface that allows the user to prepare and run coarse-grained molecular dynamics (CGMD) simulations and to analyse the trajectories.
ResponseNet v.3: revealing signaling and regulatory pathways connecting your proteins and genes across human tissues
Authors: Basha Omer , Mauer Omry , Simonovsky Eyal , Shpringer Rotem , Yeger-Lotem Esti
Published: May 2019

ResponseNet v.3 is an enhanced version of ResponseNet, a web server that is designed to highlight signaling and regulatory pathways connecting user-defined proteins and genes by using the ResponseNet network optimization approach (http://netbio.bgu.ac.il/respnet). Users run ResponseNet by defining source and target sets of proteins, genes and/or microRNAs, and by specifying a molecular interaction network (interactome). The output of ResponseNet is a sparse, high-probability interactome subnetwork that connects the two sets, thereby revealing additional molecules and interactions that are involved in the studied condition. In recent years, massive efforts were invested in profiling the transcriptomes of human tissues, enabling the inference of human tissue interactomes. ResponseNet v.3 expands ResponseNet2.0 by harnessing ∼11,600 RNA-sequenced human tissue profiles made available by the Genotype-Tissue Expression consortium, to support context-specific analysis of 44 human tissues. Thus, ResponseNet v.3 allows users to illuminate the signaling and regulatory pathways potentially active in the context of a specific tissue, and to compare them with active pathways in other tissues. In the era of precision medicine, such analyses open the door for tissue- and patient-specific analyses of pathways and diseases.
A Proof of Concept for Applying the Radicchi Index (hf ) to Compare Academic Productivity and Scientific Impact Among Medical Specialties
Authors: Do Truong H , Miller Catherine , Low Walter C , Haines Stephen J
Published: May 2019

Many indices have been developed to assess the impact of scientific publications by investigators, disciplines, and institutions. The h-index has emerged as a leading tool in the assessment of the productivity of authors. Differences in publication and citation opportunity among specialties create inappropriate conclusions when the h-index is used to compare authors across different disciplines. An alternative, the Radicchi index, hf
, has been proposed to assess the impact of publications across disciplines. We curated a database of all articles published from 2002 to 2015 from the 3 highest impact factor medical journals: New England Journal of Medicine (NEJM), the Lancet, and the Journal of American Medical Association (JAMA). With this database, articles were categorized into medical subspecialties. We calculated the respective h-index and Radicchi index of each specialty. We found that the Radicchi index eliminated variability associated with publication and citation opportunity between different specialties when compared to the h-index. The Radicchi index is a useful measure of scientific impact and productivity that advances the h-index by allowing interspecialty comparisons. There remains a need to define a researcher's specialty designation especially if he/she conducts multidisciplinary research.
Effect of reducing dietary advanced glycation end products on obesity-associated complications: a systematic review
Authors: Ribeiro Priscila V M , Tavares Juliana F , Costa Mirian A C , Mattar Jéssica B , Alfenas Rita C G
Published: May 2019

Context

Consumption of dietary advanced glycation end products (AGEs) is associated with oxidative stress, inflammation, and other chronic conditions commonly associated with obesity.

Objective

To analyze the effects of dietary AGEs on complications associated with obesity.

Data sources

This systematic review was conducted and reported according to PRISMA guidelines. The PubMed, Cochrane, and Scopus databases were searched, using the terms “advanced glycation end products,” “overweight,” and “obesity.” The last search was performed in October 2018.

Data extraction

Six studies that evaluated the effects of low-AGE and high-AGE diets were included in the review. The duration of the studies ranged from 1 day to 12 weeks. A comparison of all the compiled data was conducted by the authors.

Data analysis

Circulating and urinary AGE markers, besides soluble receptor for AGEs, were considered as the primary outcomes. The secondary outcomes were cardiometabolic, inflammatory, glycemic, anthropometric, and renal markers.

Conclusions

AGE-RAGE interactions can activate the NF-κB (nuclear factor kappa B) signaling pathway and inhibit the PI3K-AKT pathway in adipocytes, which may explain their association with chronic diseases. This interaction can be considered as a novel explanation for the pathogenesis of obesity. AGEs can also be used as a biomarker for monitoring responses to dietary interventions in overweight and obese people.

Systematic Review Registration

PROSPERO registration no. CRD42018082745.
Effect of vitamin D supplementation on serum lipid profiles: a systematic review and meta-analysis
Authors: Dibaba Daniel T
Published: May 2019

Context

Vitamin D deficiency is highly prevalent across the world. The existing evidence suggests vitamin D may have beneficial effects on serum lipid profiles and thus cardiovascular health.

Objective

The objective of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on serum lipid profiles.

Data Source

Original randomized controlled trials (RCTs) examining the effect of vitamin D supplementation on serum lipid profiles and published before July 2018 were identified by searching online databases, including PubMed, Google Scholar, and ScienceDirect, using a combination of relevant keywords.

Data Extraction

Data on study characteristics, effect size, measure of variation, type of vitamin D supplementation, and duration of follow-up were extracted by the author.

Data Analysis

PRISMA guidelines for systematic reviews were followed. Random effects (DerSimonian and Laird [D-V)] models were used to pool standardized mean differences in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides between the active and the placebo arms of RCT studies. Between-study heterogeneities were assessed using Cochrane Q and I2, and publication bias was assessed using Begg’s test, Egger’s test, and funnel plot.

Results

A total of 41 RCTs comprising 3434 participants (n = 1699 in the vitamin D supplementation arm and n = 1735 in the placebo arm) were identified and included in the meta-analysis. Approximately 63.4% of study participants were women, with 14 studies conducted entirely among women. Approximately 24% of the trials had follow-up duration >6 months, whereas the remaining 76% had follow-up duration of <6 months. The standardized mean differences (SMDs) and 95% confidence intervals (CIs) for comparing the change from baseline to follow-up between the vitamin D supplementation arm and the placebo (control) arm were as follows: total cholesterol = –0.17 (–0.28 to –0.06); LDL cholesterol = –0.12 (–0.23 to –0.01); triglycerides = –0.12 (–0.25 to 0.01); and HDL cholesterol = –0.19 (–0.44 to 0.06). After removing a trial that was an outlier based on the magnitude of the effect size, the SMD for triglycerides was –0.15 (–0.24 to –0.06) and that for HDL cholesterol was –0.10 (–0.28 to 0.09). The improvements in total cholesterol and triglycerides were more pronounced in participants with baseline vitamin D deficiency.

Conclusions

Vitamin D supplementation appeared to have a beneficial effect on reducing serum total cholesterol, LDL cholesterol, and triglyceride levels but not HDL cholesterol levels. Vitamin D supplementation may be useful in hypercholesterolemia patients with vitamin D insufficiency who are at high risk of cardiovascular diseases.
Evidence for Magma–Wall Rock Interaction in Carbonatites from the Kaiserstuhl Volcanic Complex (Southwest Germany)
Authors: Giebel R J , Parsapoor A , Walter B F , Braunger S , Marks M A W , Wenzel T , Markl G
Published: May 2019

The mineralogy and mineral chemistry of the four major sövite bodies (Badberg, Degenmatt, Haselschacher Buck and Orberg), calcite foidolite/nosean syenite xenoliths (enclosed in the Badberg sövite only) and rare extrusive carbonatites of the Kaiserstuhl Volcanic Complex in Southern Germany provide evidence for contamination processes in the carbonatitic magma system of the Kaiserstuhl. Based on textures and composition, garnet and clinopyroxene in extrusive carbonatites represent xenocrysts entrained from the associated silicate rocks. In contrast, forsterite, monticellite and mica in sövites from Degenmatt, Haselschacher Buck and Orberg probably crystallized from the carbonatitic magma. Clinopyroxene and abundant mica crystallization in the Badberg sövite, however, was induced by the interaction between calcite foidolite xenoliths and the carbonatite melt. Apatite and micas in the various sövite bodies reveal clear compositional differences: apatite from Badberg is higher in REE, Si and Sr than apatite from the other sövite bodies. Mica from Badberg is biotite- and comparatively Fe2+-rich (Mg# = 72–88). Mica from the other sövites, however, is phlogopite (Mg# up to 97), as is typical of carbonatites in general. The typical enrichment of Ba due to the kinoshitalite substitution is observed in all sövites, although it is subordinate in the Badberg samples. Instead, Badberg biotites are strongly enriched in IVAl (eastonite substitution) which is less important in the other sövites. The compositional variations of apatite and mica within and between the different sövite bodies reflect the combined effects of fractional crystallization and carbonatite-wall rock interaction during emplacement. The latter process is especially important for the Badberg sövites, where metasomatic interaction released significant amounts of K, Fe, Ti, Al and Si from earlier crystallized nosean syenites. This resulted in a number of mineral reactions that transformed these rocks into calcite foidolites. Moreover, this triggered the crystallization of compositionally distinct mica and clinopyroxene crystals around the xenoliths and within the Badberg sövite itself. Thus, the presence and composition of clinopyroxene and mica in carbonatites may be useful indicators for contamination processes during their emplacement. Moreover, the local increase of silica activity during contamination enabled strong REE enrichment in apatite via a coupled substitution involving Si, which demonstrates the influence of contamination on REE mineralization in carbonatites.
Public Health and the Virtues of Responsibility, Compassion and Humility
Authors: Nihlén Fahlquist Jessica
Published: May 2019

In contrast to medical care, which is focused on the individual patient, public health is focused on collective health. This article argues that, in order to better protect the individual, discussions of public health would benefit from incorporating the insights of virtue ethics. There are three reasons to for this. First, the collective focus may cause neglect of the effects of public health policy on the interests and rights of individuals and minorities. Second, whereas the one-on-one encounters in medical care facilitate a compassionate and caring attitude, public health involves a distance between professionals and the public. Therefore, public health professionals must use imagination and care to evaluate the effects of policies on individuals. Third, the relationship between public health professionals and the people who are affected by the policies they design is characterized by power asymmetry, demanding a high level of responsibility from those who wield them.

Against this background, it is argued that public health professionals should develop the virtues of responsibility, compassion and humility. The examples provided, i.e. breastfeeding information and vaccination policy, illustrate the importance of these virtues, which needed for normative as well as instrumental reasons, i.e. as a way to restore trust.
A NEW THERMOLUMINESCENCE GENERAL ORDER GLOW CURVE FIT FUNCTION CONSIDERING THERMAL QUENCHING EFFECT
Authors: Harooni S , Zahedifar M , Sadeghi E , Ahmadian Z
Published: May 2019

A new thermoluminescence (TL) general order glow curve fit function in terms of the intensity of peak maximum, Im and the peak temperature, Tm is presented in which thermal quenching (TQ) effect has been taken into account. Also, the conventional general order model and the new presented function were fitted to the glow peak 5 of LiF:Mg,Ti (TLD-100) and the kinetic parameters were obtained for different heating rates as the results of fitting procedure. It was found that increasing the heating rate, which makes the TQ more prominent, causes more divergence between the kinetic parameters extracted by applying two models. Considering that the TL intensity and the glow peak area reduce with shifting the glow peak to higher temperatures as a result of TQ, the new presented function gives more reliable results for the kinetic parameters.
A CRISPR/Cas9 Whole-Genome Screen Identifies Genes Required for Aryl Hydrocarbon Receptor-Dependent Induction of Functional CYP1A1
Authors: Sundberg Christopher D , Hankinson Oliver
Published: May 2019

Environmental pollutants including halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons, including benzo[a]pyrene, exert their deleterious effects through the activation of the aryl hydrocarbon receptor (AHR) and by the resulting transcription of genes not yet fully identified. Ligand-bound AHR translocates from cytoplasm to nucleus, where it dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT) protein. The AHR/ARNT dimer binds to enhancer regions of responsive genes to activate transcription. AHR also mediates carcinogenesis caused by PAHs, likely via CYP1A1, CYP1A2, and CYP1B1, which are massively induced by activated AHR in many tissues and generate carcinogenic electrophilic derivatives of PAHs. In the current study, we have used the mouse GeCKOv2 genome-wide CRISPR/Cas9 library to identify novel genes in the AHR pathway by taking advantage of a B[a]P selection assay that we previously used to identify core AHR pathway genes in Hepa-1c1c7 murine hepatoma cells. Besides Ahr, Arnt, and Cyp1a1, we report the identification of multiple additional putative AHR pathway genes including several that we validated. These include cytochrome P450 reductase (Por), which mediates redox regeneration of cytochromes P450, and 5 genes of the heme biosynthesis pathway: delta-aminolevulinate synthase 1 (Alas1), porphobilinogen deaminase (Hmbs), uroporphyrinogen decarboxylase (Urod), coproporphyrinogen oxidase (Cpox), and ferrochelatase (Fech): heme being an essential prosthetic group of cytochrome P450 proteins. Notably, several of these genes were identified by GeCKO screening, despite not being identifiable by reverse genetics approaches. This indicates the power of high-sensitivity genome-wide genetic screening for identifying genes in the AHR pathway.
Patient Preferences Post IUD Insertion [1G]
Authors: Abern Lauren , de Guzman Glendell , Kiely Kristen , Packard Adelaide , Maguire Karla
Published: May 2019

INTRODUCTION:

Although the intrauterine device (IUD) is a safe and highly effective method of contraception, patients have concerns about complications. Our objective is to characterize patient apprehensions with IUD insertion and determine if string checks or closer follow-up will help to alleviate these concerns.

METHODS:

Individuals 18 and older presenting for IUD insertion participated in an online survey about reproductive history, reasons for choosing an IUD and concerns for complications.

RESULTS:

603 surveys were completed. The mean age was 28.6 (SD 6.6). The majority (432, 72%) was Caucasian and graduated from college (507, 84%). All participants had insurance (603, 100%). The most common reasons for choosing an IUD were because it was long-acting (501, 84%) and low maintenance (525, 88%). Participants were most concerned about an embedded IUD (285, 53%), uterine perforation (271, 51%), and expulsion (235, 44%) as potential complications. Although only 334 (57%) were counseled about string checks, 436 (74%) plan on performing monthly string checks to determine if their IUD is in place. 424 (72%) desired to return to the office in 4-6 weeks for an IUD check.

CONCLUSION:

Potential complications such as uterine perforation and embedded IUD are primary concerns for those choosing an IUD. Most participants prefer to perform monthly string checks and an office visit for an IUD check. Based on this data, providers should strongly consider counseling patients about string checks and offering an appointment for an IUD check 4-6 weeks after placement for patient reassurance.
A Prospective Investigation of Inflammation and Uric Acid in Preeclampsia [15G]
Authors: Psoinos Rachel , Leung Katherine , Dumont Tina , Simas Tiffany Moore
Published: May 2019

INTRODUCTION:

The role of uric acid in preeclampsia (PEC) is controversial. We hypothesize that women with PEC express a pro-inflammatory cytokine profile compared to controls related to uricemia.

METHODS:

In an IRB approved secondary analysis of a two-center prospective cohort study of women with PEC risk factors, maternal serum was collected in second and third trimesters. PEC cases were matched with controls on age, body mass index, fetal number, and chronic hypertension. Women with gestational hypertension (GHTN) were matched to PEC cases. Multiplex technology analyzed inflammatory cytokines at diagnosis and at delivery if delayed. Serum uric acid levels were extracted from the medical record.

RESULTS:

Of 258 subjects, 26 PEC and 15 GHTN cases were identified. Of PEC cases, 53.8% were diagnosed preterm and 30.8% had CHTN. PEC cases delivered earlier than controls (P=.020). Unadjusted linear regression showed significant decrease in interleukin-18 (IL-18) in PEC versus controls (P=.033) and in monocyte chemoattractant protein-1 (MCP-1) in PEC versus GHTN cases (P=.022). By multivariable regression, covariates of gestational age, diabetes, PEC history and parity were not significant confounders. Qualitatively, uric acid demonstrated linear increase over pregnancy in PEC whereas controls had more abrupt increases near term.

CONCLUSION:

PEC cases expressed different levels of MCP-1 and IL-18 compared to controls and GHTN, suggesting a unique inflammatory state of PEC. Contrary to our hypothesis, select pro-inflammatory markers were lower in PEC. A larger population may clarify whether differences in subgroups of PEC or timing of sampling relative to diagnosis could explain findings.