bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptogramer: an R/Bioconductor package for transcriptional analysis based on protein–protein interaction
Authors: Morais Diego A A , Almeida Rita M C , Dalmolin Rodrigo J S 
Published: January 2019

Abstract

Motivation
Several freely available tools perform analysis using algorithms developed to identify significant variation of gene expression individually. The transcriptogramer R package uses protein–protein interaction to perform differential expression of functionally associated genes. The software assesses expression profile of entire genetic systems and reveals which biological systems are significantly altered in case-control designed transcriptome experiments.

Results
R/Bioconductor transcriptogramer package projects expression values on an ordered gene list to perform topological analysis, differential expression and gene ontology enrichment analysis, independently of data platform or operating system.

Availability and implementation
http://bioconductor.org/packages/transcriptogramer.

Supplementary information
Supplementary data are available at Bioinformatics online.
MULTiPly: a novel multi-layer predictor for discovering general and specific types of promoters
Authors: Zhang Meng , Li Fuyi , Marquez-Lago Tatiana T , Leier André , Fan Cunshuo , Kwoh Chee Keong , Chou Kuo-Chen , Song Jiangning , Jia Cangzhi 
Published: January 2019

Abstract

Motivation
Promoters are short DNA consensus sequences that are localized proximal to the transcription start sites of genes, allowing transcription initiation of particular genes. However, the precise prediction of promoters remains a challenging task because individual promoters often differ from the consensus at one or more positions.

Results
In this study, we present a new multi-layer computational approach, called MULTiPly, for recognizing promoters and their specific types. MULTiPly took into account the sequences themselves, including both local information such as k-tuple nucleotide composition, dinucleotide-based auto covariance and global information of the entire samples based on bi-profile Bayes and k-nearest neighbour feature encodings. Specifically, the F-score feature selection method was applied to identify the best unique type of feature prediction results, in combination with other types of features that were subsequently added to further improve the prediction performance of MULTiPly. Benchmarking experiments on the benchmark dataset and comparisons with five state-of-the-art tools show that MULTiPly can achieve a better prediction performance on 5-fold cross-validation and jackknife tests. Moreover, the superiority of MULTiPly was also validated on a newly constructed independent test dataset. MULTiPly is expected to be used as a useful tool that will facilitate the discovery of both general and specific types of promoters in the post-genomic era.

Availability and implementation
The MULTiPly webserver and curated datasets are freely available at http://flagshipnt.erc.monash.edu/MULTiPly/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies
Authors: Seidah Nabil G , Prat Annik , Pirillo Angela , Catapano Alberico Luigi , Norata Giuseppe Danilo 
Published: January 2019

AbstractSince the discovery of the role of proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of low-density lipoprotein cholesterol (LDL-C) in 2003, a paradigm shift in the treatment of hypercholesterolaemia has occurred. The PCSK9 secreted into the circulation is a major downregulator of the low-density lipoprotein receptor (LDLR) protein, as it chaperones it to endosomes/lysosomes for degradation. Humans with loss-of-function of PCSK9 exhibit exceedingly low levels of LDL-C and are protected from atherosclerosis. As a consequence, innovative strategies to modulate the levels of PCSK9 have been developed. Since 2015 inhibitory monoclonal antibodies (evolocumab and alirocumab) are commercially available. When subcutaneously injected every 2–4 weeks, they trigger a ∼60% LDL-C lowering and a 15% reduction in the risk of cardiovascular events. Another promising approach consists of a liver-targetable specific PCSK9 siRNA which results in ∼50–60% LDL-C lowering that lasts up to 6 months (Phases II–III clinical trials). Other strategies under consideration include: (i) antibodies targeting the C-terminal domain of PCSK9, thereby inhibiting the trafficking of PCSK9-LDLR to lysosomes; (ii) small molecules that either prevent PCSK9 binding to the LDLR, its trafficking to lysosomes or its secretion from cells; (iii) complete silencing of PCSK9 by CRISPR-Cas9 strategies; (iv) PCSK9 vaccines that inhibit the activity of circulating PCSK9. Time will tell whether other strategies can be as potent and safe as monoclonal antibodies to lower LDL-C levels.
Asbestosis and silicosis hospitalizations in Italy (2001–2015): results from the National Hospital Discharge Registry
Authors: Ferrante Pierpaolo 
Published: January 2019

Abstract

Background
This work is aimed at evaluating the quality of Italian hospitalizations data about asbestosis and silicosis, assessing the impact of these diseases on the national health system and providing advice related to public health.

Methods
Italian hospital discharge data (2001–15) with diagnosis of asbestosis or silicosis were analysed by the multiple correspondence analysis and diseases epidemics were evaluated through hospitalization rates.

Results
Hospitalizations were concentrated in the northwestern area, referred mainly to males and oldest people, the most treated tumors were lung cancer and mesothelioma (for asbestosis) and cares were aimed at reducing symptoms and increasing blood oxygenation. Overall adjusted Italian hospitalization rates of asbestosis and silicosis were, respectively, 25.2 and 74.9 per 1 000 000 residents. With respect to asbestosis, hospitalizations treating silicosis reported doubled mortality (10.5 vs. 5.7%), longer stays (10.4 vs. 8.6 mean days) and older patients (77 vs. 72 years on average). Diseases rates reduced over time (with a steeper slope for silicosis) and in both fibroses increased hospital mortality (92.1% in asbestoses, 59.5% in silicoses) and percentage of urgent hospitalizations (116.0% in asbestoses, 56.6% in silicoses).

Conclusion
Hospitalizations data regarding asbestosis and silicosis are consistent. Silicosis had a higher impact than asbestosis on the Italian health system. Although data show decreasing incidence of both fibroses, multiple correspondence analysis highlights that levels of illness severity were higher in silicosis and increased over time in both diseases. Further studies investigating the effectiveness of the current health surveillance programs concerning these diseases are suggested.
Plastid Genomes and Proteins Illuminate the Evolution of Eustigmatophyte Algae and Their Bacterial Endosymbionts
Authors: Ševčíková Tereza , Yurchenko Tatiana , Fawley Karen P , Amaral Raquel , Strnad Hynek , Santos Lilia M A , Fawley Marvin W , Eliáš Marek 
Published: January 2019

Abstract
Eustigmatophytes, a class of stramenopile algae (ochrophytes), include not only the extensively studied biotechnologically important genus Nannochloropsis but also a rapidly expanding diversity of lineages with much less well characterized biology. Recent discoveries have led to exciting additions to our knowledge about eustigmatophytes. Some proved to harbor bacterial endosymbionts representing a novel genus, Candidatus Phycorickettsia, and an operon of unclear function (ebo) obtained by horizontal gene transfer from the endosymbiont lineage was found in the plastid genomes of still other eustigmatophytes. To shed more light on the latter event, as well as to generally improve our understanding of the eustigmatophyte evolutionary history, we sequenced plastid genomes of seven phylogenetically diverse representatives (including new isolates representing undescribed taxa). A phylogenomic analysis of plastid genome-encoded proteins resolved the phylogenetic relationships among the main eustigmatophyte lineages and provided a framework for the interpretation of plastid gene gains and losses in the group. The ebo operon gain was inferred to have probably occurred within the order Eustigmatales, after the divergence of the two basalmost lineages (a newly discovered hitherto undescribed strain and the Pseudellipsoidion group). When looking for nuclear genes potentially compensating for plastid gene losses, we noticed a gene for a plastid-targeted acyl carrier protein that was apparently acquired by horizontal gene transfer from Phycorickettsia. The presence of this gene in all eustigmatophytes studied, including representatives of both principal clades (Eustigmatales and Goniochloridales), is a genetic footprint indicating that the eustigmatophyte–Phycorickettsia partnership started no later than in the last eustigmatophyte common ancestor.
Canonical Gelfand–Zeitlin Modules over Orthogonal Gelfand–Zeitlin Algebras
Authors: Early Nick , Mazorchuk Volodymyr , Vishnyakova Elizaveta 
Published: January 2019

Abstract
We prove that every orthogonal Gelfand–Zeitlin algebra $U$ acts (faithfully) on its Gelfand–Zeitlin subalgebra $\Gamma $. Considering the dual module, we show that every Gelfand–Zeitlin character of $\Gamma $ is realizable in a $U$-module. We observe that the Gelfand–Zeitlin formulae can be rewritten using divided difference operators. It turns out that the action of the latter operators on $\Gamma $ gives rise to an explicit basis in a certain Gelfand–Zeitlin submodule of the dual module mentioned above. This gives, generically, both in the case of regular and singular Gelfand–Zeitlin characters, an explicit construction of simple modules, which realize the given Gelfand–Zeitlin characters.
Competition law enforcement on digital markets—lessons from recent EU case law
Authors: Kuenzler Adrian 
Published: January 2019

Abstract
This article is set against the Court of Justice of the European Union’s (CJEU) decisions in Pierre Fabre and Coty Germany GmbH, observing that in the digital economy, price is no longer the sole important parameter of competition and that competition law therefore has to reconstruct the theoretical background required to explain the tensions contained in the design of concentrated marketplaces. As the CJEU’s approach taken in Pierre Fabre and Coty shows, competition authorities and courts also need to consider the market’s distinct psychological properties when they contemplate the legal framework that governs it. The article thus explains the CJEU’s decisions not against the well-known debate about inter- and intrabrand competition but with reference to the notion of creating distinct types of ‘variety’ in the marketplace so as to enable consumers to choose not just between the alternative options that they face but also to enable them to make decisions that will shape the manner in which they think about whether they should consider alternative options at all. The article’s findings aim to advance debates about the overarching policy goals of the way in which digital markets ought to be regulated.
Evaluation of the Preliminary Validity of Misuse of Prescription Pain Medication Items from the Patient-Reported Outcomes Measurement Information System (PROMIS)®
Authors: You Dokyoung Sophia , Hah Jennifer M , Collins Sophie , Ziadni Maisa S , Domingue Ben W , Cook Karon F , Mackey Sean C 
Published: January 2019

AbstractObjectiveThe National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS)® includes an item bank for measuring misuse of prescription pain medication (PROMIS-Rx Misuse). The bank was developed and its validity evaluated in samples of community-dwelling adults and patients in addiction treatment programs. The goal of the current study was to investigate the validity of the item bank among patients with mixed-etiology chronic pain conditions.MethodA consecutive sample of 288 patients who presented for initial medical evaluations at a tertiary pain clinic completed questionnaires using the open-source Collaborative Health Outcomes Information Registry. Participants were predominantly middle-aged (M [SD] = 51.6 [15.5] years), female (62.2%), and white/non-Hispanic (51.7%). Validity was evaluated by estimating the association between PROMIS-Rx Misuse scores and scores on other measures and testing the ability of scores to distinguish among risk factor subgroups expected to have different levels of prescription pain medicine misuse (known groups analyses).ResultsOverall, score associations with other measures were as expected and scores effectively distinguished among patients with and without relevant risk factors.ConclusionThe study results supported the preliminary validity of PROMIS-Rx Misuse item bank scores for the assessment of prescription opioid misuse in patients visiting an outpatient pain clinic.
Country of birth and county of residence and association with overweight and obesity—a population-based study of 219 555 pregnancies in Norway
Authors: Torkildsen S E , Svendsen H , Räisänen S , Sole K B , Laine K 
Published: January 2019

Abstract

Background
The aim was to study the effect of country of birth, educational level and county of residence on overweight and obesity among pregnant women in Norway.

Methods
Observational study based on Medical Birth Registry Norway and Statistics Norway. The study population consisted of 219 555 deliveries in 2006–2014. Body mass index (BMI) was registered at the first antenatal care visit. Multivariate regression analysis was used to explore the study aims.

Results
Overweight (BMI 25–29.9) was recorded in 22.3% of the women, obesity (BMI ≥30) in 12.2%. Highest rates of overweight (30.8%) and obesity (13.5%) was recorded among women from the Middle East and North Africa or with no education (30.7% and 17.2%). The prevalence of overweight and obesity was 39.5% in sparsely populated counties and 26.4% for women living in Oslo. Adjusted for country of birth, education level, age, parity, smoking and marital status, the relative odds of overweight and obesity were 65% (95% CI 59–72%) higher in sparsely populated counties compared to Oslo.

Conclusions
The prevalence of overweight (BMI ≥25) was 34.5%. The factors associated with overweight were living in rural districts in Norway, lower education and being born in countries in the Middle East or Africa.
“Bargaining with Patriarchy” and “Bad Girl Femininity”: Relationship and Behaviors among Chicago Girl Gangs, 1959–62
Authors: Hughes Lorine A , Botchkovar Ekaterina V , Short James F 
Published: January 2019

AbstractThis study uses observational, social network, and self-report survey data from a large study of male gangs in Chicago, 1959–62, to examine intragroup relationships and behaviors among their female auxiliaries, particularly the Vice Ladies and Cobraettes. Unlike descriptions of the female gang as forming a cohesive “sisterhood,” our findings revealed frequent intragroup conflict and loosely connected friendship networks. Consistent with the bulk of contemporary literature, the Chicago gang girls appeared to maintain ties with one another less for affective reasons than for the benefits they provided in the streets (e.g., peer backup). Regarding their behaviors, the Chicago gang girls engaged in both socio-sexual and stereotypically male activities, including strong-arm robbery and purse-snatching. Although sex sometimes was used to gain favor with boys, we found no evidence of it being valued and rewarded with prestige among homegirls. Instead, the most sexually active girls tended to be the least popular in the gang. The implications of these findings are discussed in the context of “bad girl femininity” performed by gang girls and gang involvement as a resource for “bargaining with patriarchy.”
Community-level impacts of spatial repellents for control of diseases vectored by Aedes aegypti mosquitoes
Authors: Bosch Quirine A. ten , Wagman Joseph M. , Castro-Llanos Fanny , Achee Nicole L. , Grieco John P. , Perkins T. Alex 
Published: January 2019

AbstractSpatial repellents (SRs) reduce human-mosquito contact by preventing mosquito entrance into human-occupied spaces and interfering with host-seeking and blood-feeding. A new model to synthesize experimental data on the effects of transfluthrin on Aedes aegypti explores how SR effects interact to impact the epidemiology of diseases vectored by these mosquitoes. Our results indicate that the greatest impact on force of infection is expected to derive from the chemical’s lethal effect but delayed biting and associated negative feedbacks on the vector population could elicit substantial impact in the absence of lethality. The relative contributions of these effects depend on coverage, chemical dose, mechanism of action, and housing density. We also demonstrate potential adverse impacts of increased partial blood-feeding and reduced exiting, which could offset gains achieved by other effects. Our analysis demonstrates how small-scale experimental data can be leveraged to derive expectations of epidemiological impact of SRs deployed at larger scales.
Harmonisation of Physical Activity Variables by Indirect Validation: A Doubly Labelled Water Study
Authors: Pearce Matthew , Bishop Tom R.P. , Sharp Stephen , Westgate Kate , Venables Michelle , Wareham Nicholas J. , Brage Søren 
Published: January 2019

AbstractHarmonisation of data for pooled analysis relies on the principle of inferential equivalence between variables from different sources. Ideally, this is achieved using models of the direct relationship with gold standard criterion measures, but the necessary validation data are often unavailable. This study examines an alternative method of harmonisation by indirect validation. Starting methods were self-report or accelerometry, from which we derived indirect models of relationships with doubly labelled water (DLW)-measured physical activity energy expenditure (PAEE) using sets of two bridge equations via one of three intermediate measures. Coefficients and performance of indirect models were compared to corresponding direct validation models (linear regression of DLW-measured PAEE on starting methods). Indirect model beta coefficients were attenuated compared to direct model betas (10-63%), narrowing the range of PAEE values; attenuation was greater when bridge equations were weak. Directly and indirectly harmonised models had similar error variance but most indirectly derived values were biased at group-level. Correlations with DLW-measured PAEE were identical after harmonisation using continuous linear but not categorical models. Wrist acceleration harmonised to DLW-measured PAEE via combined accelerometry and heart rate sensing had lowest error variance (24.5%) and non-significant mean bias 0.9 (95%CI: −1.6; 3.4) kJ•day−1•kg−1. Associations between PAEE and BMI were similar for directly and indirectly harmonised values, but most fell outside the confidence interval of the criterion PAEE-to-BMI association. Indirect models can be used for harmonisation. Performance depends on the measurement properties of original data, variance explained by available bridge equations, and similarity of population characteristics.
Mixture of Experts for Predicting Antibody-Antigen Binding Affinity from Antigen Sequence
Authors: Pittala Srivamshi , Bailey-Kellogg Chris 
Published: January 2019

AbstractAntibodies provide a key mode of defense employed by the immune system to fight disease, so eliciting potent antibodies is one of the main goals in vaccine development. Antibodies are also being conceived as powerful therapeutic agents, so engineering potent antibodies is one of the main goals in biologic drug development. The power of antibodies lies in their affinity and specificity in recognizing their cognate antigens. Unfortunately, experimental techniques to determine antibody-antigen binding affinities are difficult to scale up to large sets of new antibodies and antigens. Though computational methods are suitable for large-scale prediction, current methods lack sufficient accuracy. Here, we address the problem of predicting the binding affinity of an antibody against an antigen variant based on the amino acid sequence of that antigen variant. We develop a mixture of experts approach that learns models for individual antibodies against some antigen variants, and then combines information across the antibodies in order to make accurate predictions for a wide range of new variants. In evaluation on a dataset consisting of 52 antibodies and 608 strains of HIV, the predictive accuracy of our approach is demonstrated to be significantly better than that of an existing approach. Our method provides a fast and accurate way to predict antibody-antigen binding affinity, which has the potential to expedite the study of antibody-antigen interactions for vaccine design and therapy.
Crossing fitness valleys via double substitutions within codons
Authors: Belinky Frida , Sela Itamar , Rogozin Igor B. , Koonin Eugene V. 
Published: January 2019

AbstractSingle nucleotide substitutions in protein-coding genes can be divided into synonymous (S), with little fitness effect, and non-synonymous (N) ones that alter amino acids and thus generally have a greater effect. Most of the N substitutions are affected by purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases can modulate the deleterious effect of single substitutions and thus might be subject to positive selection. To elucidate the effects of selection on double substitutions in all codons, it is critical to differentiate selection from mutational biases. We approached this problem by comparing the fractions of double substitutions within codons to those of the equivalent double S substitutions in adjacent codons. Under the assumption that substitutions occur one at a time, all within-codon double substitutions can be represented as “ancestral-intermediate-final” sequences and can be partitioned into 4 classes: 1) SS: S intermediate – S final, 2) SN: S intermediate – N final, 3) NS: N intermediate – S final, 4) NN: N intermediate – N final. We found that the selective pressure on the second substitution markedly differs among these classes of double substitutions. Analogous to single S substitutions, SS evolve neutrally whereas, analogous to single N substitutions, SN are subject to purifying selection. In contrast, NS show positive selection on the second step because the original amino acid is recovered. The NN double substitutions are heterogeneous and can be subject to either purifying or positive selection, or evolve neutrally, depending on the amino acid similarity between the final or intermediate and the ancestral states. The general trend is that the second mutation compensates for the deleterious effect of the first one, resulting in frequent crossing of valleys on the fitness landscape.