bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘%svy_logistic_regression: A generic SAS® macro for simple and multiple logistic regression and creating quality publication-ready tables using survey or non-survey data
Authors: Muthusi Jacques , Mwalili Samuel , Young Peter 
Published: March 2019

AbstractIntroductionReproducible research is increasingly gaining interest in the research community. Automating the production of research manuscript tables from statistical software can help increase the reproducibility of findings. Logistic regression is used in studying disease prevalence and associated factors in epidemiological studies and can be easily performed using widely available software including SAS, SUDAAN, Stata or R. However, output from these software must be processed further to make it readily presentable. There exists a number of procedures developed to organize regression output, though many of them suffer limitations of flexibility, complexity, lack of validation checks for input parameters, as well as inability to incorporate survey design.MethodsWe developed a SAS macro,%svy_logistic_regression, for fitting simple and multiple logistic regression models. The macro also creates quality publication-ready tables using survey or non-survey data which aims to increase transparency of data analyses. It further significantly reduces turn-around time for conducting analysis and preparing output tables while also addressing the limitations of existing procedures.ResultsWe demonstrate the use of the macro in the analysis of the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a complex survey designed to assess the health and nutritional status of adults and children in the United States. The output presented here is directly from the macro and is consistent with how regression results are often presented in the epidemiological and biomedical literature, with unadjusted and adjusted model results presented side by side.ConclusionsThe SAS code presented in this macro is comprehensive, easy to follow, manipulate and to extend to other areas of interest. It can also be incorporated quickly by the statistician for immediate use. It is an especially valuable tool for generating quality, easy to review tables which can be incorporated directly in a publication.
Doberman pinschers present autoimmunity associated with functional autoantibodies: a model to study the autoimmune background of human dilated cardiomyopathy
Authors: Wess Gerhard , Wallukat Gerd , Fritscher Anna , Becker Niels-Peter , Wenzel Katrin , Müller Johannes , Schimke Ingolf 
Published: March 2019

AbstractBackgroundAutoimmunity associated with autoantibodies directed against the β1-adrenergic receptor (β1-AAB) is increasingly accepted as driving human dilated cardiomyopathy (DCM). Unfortunately, animal models of DCM are lacking, preventing our knowledge about β1-AAB autoimmunity in DCM from being extended and hindering the development of related treatment strategies.ObjectivesTo introduce an animal model, we studied Doberman pinschers, which develop cardiomyopathy (DoCM), with similarities to human DCM, with regard to their β1-AAB autoimmunity.MethodsEighty-seven DP with DoCM and 31 (at enrolment) healthy controls were analyzed for β1-AAB; the receptor binding site and sensitivity to inhibition were determined. In controls who developed cardiomyopathy during the follow-up, β1-AAB were analyzed during the DoCM progress.ResultsFifty-nine (67.8%) DoCM dogs and 19 (61.3%) controls were β1-AAB positive. Excluding the 9 controls who developed DoCM in the follow-up, β1-AAB positivity tended to be more pronounced in DoCM.From the controls who developed DoCM, 8 were β1-AAB positive (p=0.044 vs. dogs remaining healthy); their β1-AAB level increased with the cardiomyopathy progress. Overall mortality and mortality exclusively due to cardiac reasons during the study period, were higher (p=0.002; p=0037) in β1-AAB positive dogs. The dogs’ β1-AAB targeted a specific epitope centralized on the second extracellular receptor and were sensitive to inhibition by drugs already successful tested for the corresponding human autoantibody.ConclusionsDoberman pinschers presented β1-AAB associated autoimmunity similar to that driving the pathogenesis of human DCM. Consequently, DP could remove the lack of animal models available for studying β1-AAB autoimmunity in DCM.
What’s in Your Body of Water? Reducing the Psychological Distance of Pharmaceutical Pollution through Metaphoric Framing in Risk Communication (A Pilot Study)
Authors: Millarhouse Alexandra Z. , Vatovec Christine , Niles Meredith T. , Ivakhiv Adrian 
Published: March 2019

AbstractAquatic pharmaceutical pollution poses ecotoxicological risks to the environment and human health. Consumer behaviors represent a significant source of pharmaceutical compounds found in water. Thus, understanding public perceptions of aquatic pharmaceutical pollution and developing effective risk communication techniques are critical to engaging society in the type of widespread change necessary for addressing the presence of pharmaceuticals in water. This mixed-methods pilot study applies conceptual metaphor theory in conjunction with construal level theory of psychological distance to assess the relationship of metaphoric framing to perceptions of aquatic pharmaceutical contamination across four principal dimensions of psychological distance (geographic, social, and temporal distance, and uncertainty). Additionally, this study assesses the direct impact of metaphor use on concern and willingness to act, which are positively associated with perceived psychological distance. Data were collected from a convenience sample (n = 20) of university students in Burlington, Vermont using cognitive interviewing. Results indicate that participants initially perceived pharmaceutical pollution as socially and geographically distant, temporally both distant and proximal, and agreed that the issue is certain. Representing aquatic pharmaceutical contamination through metaphor significantly reduced perceived social and geographic distance, suggesting a relationship between metaphoric framing and psychological distance warranting additional research. Metaphor use did not directly nor significantly impact concern or willingness to act. Additionally, participants preferred the metaphorically-framed visual intervention to the non-metaphor visual intervention. Theoretical and practical implications of metaphor use in risk communications are discussed.
Acetylcholine release inhibits distinct excitatory inputs onto hippocampal CA1 pyramidal neurons via different cellular and network mechanisms
Authors: Goswamee Priyodarshan , McQuiston A. Rory 
Published: March 2019

AbstractIn hippocampal CA1, muscarinic acetylcholine (ACh) receptor (mAChR) activation via exogenous application of cholinergic agonists has been shown to presynaptically inhibit Schaffer collateral (SC) glutamatergic inputs in stratum radiatum (SR), and temporoammonic (TA) and thalamic nucleus reuniens (RE) glutamatergic inputs in stratum lacunosum-moleculare (SLM). However, steady-state uniform mAChR activation may not mimic the effect of ACh release in an intact hippocampal network. To more accurately examine the effect of ACh release on glutamatergic synaptic efficacy, we measured electrically evoked synaptic responses in CA1 pyramidal cells (PCs) following the optogenetic release of ACh in genetically modified mouse brain slices. The ratio of synaptic amplitudes in response to paired-pulse SR stimulation (stimulus 2/stimulus 1) was significantly reduced by the optogenetic release of ACh, consistent with a postsynaptic decrease in synaptic efficacy. The effect of ACh release was blocked by the M3 receptor antagonist 4-DAMP, the GABAB receptor antagonist CGP 52432, inclusion of GDP-β-S, cesium, QX314 in the intracellular patch clamp solution, or extracellular barium. These observations suggest that ACh release decreased SC synaptic transmission through an M3 muscarinic receptor-mediated increase in inhibitory interneuron excitability, which activate GABAB receptors and inwardly rectifying potassium channels on CA1 pyramidal cells. In contrast, the ratio of synaptic amplitudes in response to paired-pulse stimulation in the SLM was increased by ACh release, consistent with presynaptic inhibition. ACh-mediated effects in SLM were blocked by the M2 receptor antagonist AF-DX 116, presumably located on presynaptic terminals. Therefore, our data indicate that ACh release differentially modulates excitatory inputs in SR and SLM of CA1 through different cellular and network mechanisms.
Frequent birth ofde novogenes in the compact yeast genome
Authors: Blevins William R. , Ruiz-Orera Jorge , Messeguer Xavier , Blasco-Moreno Bernat , Villanueva-Cañas José Luis , Espinar Lorena , Díez Juana , Carey Lucas B. , Mar Albà M. 
Published: March 2019

AbstractEvidence has accumulated that some genes originate directly from previously non-genic sequences, orde novo, rather than by the duplication or fusion of existing genes. However, howde novogenes emerge and eventually become functional is largely unknown. Here we perform the first study onde novogenes that uses transcriptomics data from eleven different yeast species, all grown identically in both rich media and in oxidative stress conditions. The genomes of these species are densely-packed with functional elements, leaving little room for the co-option of genomic sequences into new transcribed loci. Despite this, we find that at least 213 transcripts (~5%) have arisende novoin the past 20 million years of evolution of baker’s yeast-or approximately 10 new transcripts every million years. Nearly half of the total newly expressed sequences are generated from regions in which both DNA strands are used as templates for transcription, explaining the apparent contradiction between the limited ‘empty’ genomic space and high rate ofde novogene birth. In addition, we find that 40% of thesede novotranscripts are actively translated and that at least a fraction of the encoded proteins are likely to be under purifying selection. This study shows that even in very highly compact genomes,de novotranscripts are continuously generated and can give rise to new functional protein-coding genes.
CMKLR1-targeting peptide tracers for PET/MR imaging of breast cancer
Authors: Erdmann Sarah , Niederstadt Lars , Koziolek Eva Jolanthe , Castillo Gómez Juan Daniel , Prasad Sonal , Wagener Asja , von Hacht Jan Lennart , Hallmann Sandy , Exner Samantha , Bandholtz Sebastian , Beindorff Nicola , Brenner Winfried , Grötzinger Carsten 
Published: March 2019

AbstractMolecular targeting remains to be a promising approach in cancer medicine. Knowledge about molecular properties such as overexpression of G protein-coupled receptors (GPCRs) is thereby offering a powerful tool for tumor-selective imaging and treatment of cancer cells. We utilized chemerin-based peptides for CMKLR1 receptor targeting in a breast cancer xenograft model. By conjugation with radiolabeled chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), we obtained a family of highly specific and affine tracers for hybridin vivoimaging with positron emission tomography (PET)/ magnetic resonance (MR) and concomitant biodistribution studies.MethodsWe developed five highly specific and affine peptide tracers targeting CMKLR1 by linker-based conjugation of chemerin peptide analogs (CG34 and CG36) with radiolabeled (68Ga) chelator DOTA. Our established xenograft model with target-positive DU4475 and negative A549 tumors in immunodeficient nude mice enabled CMKLR1-specific imagingin vivo. Therefore, we acquired small animal PET/MR images, assessed biodistribution byex vivomeasurements and investigated the tracer specificity by blocking experiments.ResultsThe family of five CMKLR1-targeting peptide tracers demonstrated high biological activity and affinityin vitrowith EC50and IC50values being below 2 nM. Our target-positive (DU4475) and target-negative (A549) xenograft model could be confirmed byex vivoanalysis of CMKLR1 expression and binding. After preliminary PET imaging, the three most promising tracers68Ga-DOTA-AHX-CG34,68Ga-DOTA-KCap-CG34 and68Ga-DOTA-ADX-CG34 with apparent DU4475 tumor uptake were further analyzed. Hybrid PET/MR imaging along with concomitant biodistribution studies revealed distinct CMKLR1-specific uptake (5.1% IA/g, 4.5% IA/g and 6.2% IA/g 1 h post-injection) of our targeted tracers in DU4475 tumor tissue. More strikingly, the tumor uptake could be blocked by excess of unlabeled peptide (6.4-fold, 7.2-fold and 3.4-fold 1 h post-injection) and further confirmed the CMKLR1 specificity. As our five tracers, each with particular degree of hydrophobicity, showed different results regarding tumor uptake and organ distribution, we identified these three tracers with moderate, balanced properties to be the most potent in receptor-mediated tumor targeting.ConclusionWith the breast cancer cell line DU4475, we established a model endogenously expressing our target CMKLR1 to evaluate our chemerin-based peptide tracers as highly affine and specific targeting agents. Eventually, we demonstrated the applicability of our68Ga-labeled tracers by visualizing CMKLR1-positive breast cancer xenografts in PET/MR imaging and thus developed promising theranostics for tumor treatment.
Estimating relatedness between malaria parasites
Authors: Taylor Aimee R. , Jacob Pierre E. , Neafsey Daniel E. , Buckee Caroline O. 
Published: March 2019

1.AbstractUnderstanding the relatedness of individuals within or between populations is a common goal in biology. Increasingly, relatedness features in genetic epidemiology studies of pathogens. These studies are relatively new compared to those in humans and other organisms, but are important for designing interventions and understanding pathogen transmission. Only recently have researchers begun to routinely apply relatedness to apicomplexan eukaryotic malaria parasites, and to date have used a range of different approaches on an ad hoc basis. It remains unclear how to compare different studies, therefore, and which measures to use. Here, we systematically compare measures based on identity-by-state and identity-by-descent using a globally diverse data set of malaria parasites,Plasmodium falciparumandPlasmodium vivax, and provide marker requirements for estimates based on identity-by-descent. We formally show that the informativeness of polyallelic markers for relatedness inference is maximised when alleles are equifrequent. Estimates based on identity-by-state are sensitive to allele frequencies, which vary across populations and by experimental design. For portability across studies, we thus recommend estimates based on identity-by-descent. To generate reliable estimates, we recommend approximately 200 biallelic or 100 polyallelic markers. Confidence intervals illuminate inference across studies based on different sets of markers. These marker requirements, unlike many thus far reported, are immediately applicable to haploid malaria parasites and other haploid eukaryotes. This is the first attempt to provide rigorous analysis of the reliability of, and requirements for, relatedness inference in malaria genetic epidemiology, and will provide a basis for statistically informed prospective study design and surveillance strategies.
Nbs1 Mediates Assembly and Activity of the Mre11 complex
Authors: Kim Jun Hyun , Penson Alexander , Taylor Barry S. , Petrini John H.J. 
Published: March 2019

AbstractWe derived a mouse model in which a mutant form of Nbs1 (Nbs1mid8) exhibits severely impaired binding to the Mre11-Rad50 core of the Mre11 complex. TheNbs1mid8allele was expressed exclusively in hematopoietic lineages (inNbs1-/mid8vavmice). UnlikeNbs1flox/floxvavmice, which are Nbs1 deficient in the bone marrow,Nbs1-/mid8vavmice were viable.Nbs1-/mid8vavhematopoiesis was profoundly defective, exhibiting reduced cellularity of thymus and bone marrow, and stage specific blockage of B cell development. Within six months,Nbs1-/mid8mice developed highly penetrant T cell leukemias.Nbs1-/mid8vavleukemias recapitulated mutational features of human T-ALL, containing mutations inNotch1, Trp53, Bcl6, Bcor, andIkzf1, suggesting thatNbs1mid8mice may provide a venue to examine the relationship between the Mre11 complex and oncogene activation in the hematopoietic compartment. Genomic analysis ofNbs1-/mid8vavmalignancies showed focal amplification of 9qA2, causing overexpression ofMRE11andCHK1. We propose that overexpression compensates for the meta-stable Mre11-Nbs1mid8interaction, and that selection pressure for overexpression reflects the essential role of Nbs1 in promoting assembly and activity of the Mre11 complex.
Looking for a reference for large datasets: relative reliability of visual and automatic sleep scoring
Authors: Berthomier C. , Muto V. , Schmidt C. , Vandewalle G. , Jaspar M. , Devillers J. , Gaggioni G. , Chellappa S. L. , Meyer C. , Phillips C. , Salmon E. , Berthomier P. , Prado J. , Benoit O. , Brandewinder M. , Mattout J. , Maquet J. 
Published: March 2019

AbstractStudy ObjectivesNew challenges in sleep science require to describe fine grain phenomena or to deal with large datasets. Beside the human resource challenge of scoring huge datasets, the inter- and intra-expert variability may also reduce the sensitivity of such studies. Searching for a way to disentangle the variability induced by the scoring method from the actual variability in the data, visual and automatic sleep scorings of healthy individuals were examined.MethodsA first dataset (DS1, 4 recordings) scored by 6 experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to investigate intra-expert variability. Percentage agreements and Conger’s kappa were derived from epoch-by-epoch comparisons on pairwise, consensus and majority scorings.ResultsOn DS1 the number of epochs of agreement decreased when the number of expert increased, in both majority and consensus scoring, where agreement ranged from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 intra-expert variability was evidenced by the kappa systematic decrease between autoscoring and each single expert between datasets (0.75 to 0.70).ConclusionsVisual scoring induces inter- and intra-expert variability, which is difficult to address especially in big data studies. When proven to be reliable and if perfectly reproducible, autoscoring methods can cope with intra-scorer variability making them a sensible option when dealing with large datasets.Statement of SignificanceWe confirmed and extended previous findings highlighting the intra- and inter-expert variability in visual sleep scoring. On large datasets those variability issues cannot be completely addressed by neither practical nor statistical solutions such as group training, majority or consensus scoring.When an automated scoring method can be proven to be as reasonably imperfect as visual scoring but perfectly reproducible, it can serve as a reliable scoring reference for sleep studies.
PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome
Authors: Ahier Arnaud , Cummins Nadia , Dai Chuan-Yang , Götz Jürgen , Zuryn Steven 
Published: March 2019

AbstractIn multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels, such as neurons. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. Together, these results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.
A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures
Authors: Diossy Miklos , Sztupinszki Zsofia , Borcsok Judit , Krzystanek Marcin , Tisza Viktoria , Spisak Sandor , Rusz Orsolya , Timar Jozsef , Csabai István , Moldvay Judit , Pedersen Anders Gorm , Szuts David , Szallasi Zoltan 
Published: March 2019

AbstractBackgroundConsistent with their assumed mechanism of action, PARP inhibitors show significant therapeutic efficacy in breast, ovarian and prostate cancer, which are the solid tumor types most often associated with the loss of function of key homologous recombination genes. It remains unknown, however, how frequent homologous recombination deficiency (HRD) is in other solid tumor types. Since it is well established, that HRD induces specific DNA aberration profiles and genomic scars that can be captured by various next-generation sequencing (NGS) based biomarkers, it is possible to assess the presence or absence of this DNA repair pathway aberration in any given tumor biopsy.MethodsWe derived the various HRD associated mutational signatures from whole genome and whole exome sequencing data in the lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) cases from TCGA, in a patient of ours with stage IVA lung cancer with exceptionally good response to platinum-based therapy and in lung cancer cell lines.ResultsWe have found evidence that a subset of the investigated cases shows robust signs of HR deficiency, some of which exhibiting similar patterns to those with a complete loss of function of either BRCA1 or BRCA2 genes, however, without any signs of genetic alterations being present in either of those genes. The extreme platinum responder case also showed a robust HRD associated genomic mutational profile. HRD associated mutational signatures were also associated with PARP inhibitor sensitivity in lung cancer cell lines.ConclusionsLung cancer cases with high levels of HRD associated mutational signatures could be candidates for PARP inhibitor treatment, and in general, the prioritization of patients for clinical trials might be achieved using the combined analysis of the HRD-related next-generation sequencing-based mutational signatures.
Visual recognition of the female body axis drives spatial elements of male courtship in Drosophila melanogaster
Authors: McKinney Ross M , Ben-Shahar Yehuda 
Published: March 2019

SummaryLike other mating behaviors, the courtship ritual exhibited by male Drosophila towards a virgin female is comprised of spatiotemporal sequences of innate behavioral elements. Yet, the specific stimuli and neural circuits that determine when and where males release individual courtship elements are not well understood. Here, we investigated the role of visual object recognition in the release of specific behavioral elements during bouts of male courtship. By using a computer vision and machine learning based approach for high-resolution analyses of the male courtship ritual, we show that the release of distinct behavioral elements occur at stereotyped locations around the female and depends on the ability of males to recognize visual landmarks present on the female. Specifically, we show that independent of female motion, males utilize unique populations of visual projection neurons to recognize the eyes of a target female, which is essential for the release of courtship behaviors at their appropriate spatial locations. Together, these results provide a mechanistic explanation for how relatively simple visual cues could play a role in driving both spatially- and temporally-complex social interactions.