bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian two-way latent structure model for genomic data integration reveals few pan-genomic cluster subtypes in a breast cancer cohort
Authors: Swanson David M , Lien Tonje , Bergholtz Helga , Sørlie Therese , Frigessi Arnoldo 
Published: May 2019

Abstract

Motivation
Unsupervised clustering is important in disease subtyping, among having other genomic applications. As genomic data has become more multifaceted, how to cluster across data sources for more precise subtyping is an ever more important area of research. Many of the methods proposed so far, including iCluster and Cluster of Cluster Assignments (COCAs), make an unreasonable assumption of a common clustering across all data sources, and those that do not are fewer and tend to be computationally intensive.

Results
We propose a Bayesian parametric model for integrative, unsupervised clustering across data sources. In our two-way latent structure model, samples are clustered in relation to each specific data source, distinguishing it from methods like COCAs and iCluster, but cluster labels have across-dataset meaning, allowing cluster information to be shared between data sources. A common scaling across data sources is not required, and inference is obtained by a Gibbs Sampler, which we improve with a warm start strategy and modified density functions to robustify and speed convergence. Posterior interpretation allows for inference on common clusterings occurring among subsets of data sources. An interesting statistical formulation of the model results in sampling from closed-form posteriors despite incorporation of a complex latent structure. We fit the model with Gaussian and more general densities, which influences the degree of across-dataset cluster label sharing. Uniquely among integrative clustering models, our formulation makes no nestedness assumptions of samples across data sources so that a sample missing data from one genomic source can be clustered according to its existing data sources. We apply our model to a Norwegian breast cancer cohort of ductal carcinoma in situ and invasive tumors, comprised of somatic copy-number alteration, methylation and expression datasets. We find enrichment in the Her2 subtype and ductal carcinoma among those observations exhibiting greater cluster correspondence across expression and CNA data. In general, there are few pan-genomic clusterings, suggesting that models assuming a common clustering across genomic data sources might yield misleading results.

Availability and implementation
The model is implemented in an R package called twl (‘two-way latent’), available on CRAN. Data for analysis are available within the R package.

Supplementary information
Supplementary data are available at Bioinformatics online.
The fallacy of biphasic growth allometry for the vertebrate brain
Authors: Packard Gary C 
Published: May 2019

AbstractThe concept of biphasic, loglinear growth of the vertebrate brain is based on graphical displays of logarithmic transformations of the original measurements. Such displays commonly give the appearance of two distinct mathematical distributions – one set of observations following a steep trajectory at the low end of the size range and another set following a shallow trajectory at the high end. However, the appearance of two distributions is an artefact resulting from the logarithmic transformations. Observations of brain mass vs. body mass in each of the eight vertebrate species examined in the current investigation conform to a single mathematical distribution that is well described by a single equation fitted to the original, untransformed data by non-linear regression. Data for carp, chickens, kangaroos and rabbits are described by three-parameter power equations whereas those for dolphins and primates are described by exponential functions that rise rapidly to a maximum. The brain continues to grow throughout life in carp, chickens, kangaroos and rabbits but not in dolphins and primates. Future investigations of relative growth of the brain should be based on graphical and analytical study of observations expressed on the native mathematical scale.
Constructing Causal Understanding in Complex Systems: Epistemic Strategies Used by Ecosystem Scientists
Authors: Kamarainen Amy M , Grotzer Tina A 
Published: May 2019

AbstractMoving from a correlational to a causal account involves epistemological assumptions in any discipline. It presents particular challenges when phenomena involve multiple causes, time lags, feedback loops, or thresholds, as is the case in ecosystem science. Although reductionist approaches may contribute to explanatory efforts, investigation in ecosystems science requires a systems perspective. Understanding how ecosystem scientists arrive at causal accounts—and importantly, that they do—is critical to public understanding of science. Interviews with ten ecosystem scientists revealed the strategies and habits of mind that ecosystem scientists bring to examining complex systems. The scientists described challenges in conducting experiments at relevant scales and the epistemic strategies employed in response. The themes included constructing a body of evidence using multiple approaches, integrating results through statistical and process-based models, measuring and describing variability, conducting experiments in context, thinking across levels, considering the limits to generalizability, and exercising epistemic fluency. We discuss implications for K–20 education.
Intraductal fulvestrant for therapy of ERα-positive ductal carcinoma in situ of the breast: a preclinical study
Authors: Wang Guannan , Chen Chuang , Pai Priya , Korangath Preethi , Sun Shengrong , Merino Vanessa F , Yuan Jingping , Li Suping , Nie Guangjun , Stearns Vered , Sukumar Saraswati 
Published: May 2019

AbstractMammographic screening for breast cancer has led to increased detection of ductal carcinoma in situ (DCIS) and a reappraisal of the necessity of aggressive treatment with their attendant toxicities for a preneoplastic lesion. Fulvestrant, a selective estrogen receptor degrader, is very effective in the treatment of estrogen receptor positive (ER+) breast cancer, but delivery by the painful intramuscular (i.m) route is limiting. We hypothesized that intraductal (i.duc) administration of fulvestrant will provide a direct, safe and effective treatment for DCIS. Mice bearing mammary ductal xenografts of ER+, luciferase-tagged MCF-7 breast cancer cells were administered vehicle or fulvestrant i.m or i.duc. I.duc MCF-7-luc tumors in mice treated with fulvestrant i.duc or i.m grew significantly slower than vehicle control. Whole mount analysis and histopathology showed that i.duc fulvestrant achieved significantly larger cancer-free areas. Western blot analysis showed reduced levels of estrogen receptor alpha (ERα) and its downstream targets, c-Myc and Cyclin D1, and increased levels of ERβ, which is known to inhibit ERα function. Immunohistochemical analysis of tumor sections showed that Ki67 and ERα protein levels decreased by 3-fold, and neoangiogenesis was inhibited by i.duc fulvestrant treatment. I.duc fulvestrant also reduced outgrowth of ERα+, autochthonous N-methyl-N-nitrosourea-induced mammary tumors in rats. Overall, we have shown that i.duc fulvestrant was significantly more effective than, or equivalent in action to i.m fulvestrant in two preclinical models of breast cancer. These studies provide evidence for a novel and safe route for fulvestrant therapy of DCIS and prevention of breast cancer. This preclinical study provides a strong basis for conducting clinical trials for DCIS and early breast cancer.
Quality of Life in Patients With Olfactory Loss Is Better Predicted by Flavor Identification Than by Orthonasal Olfactory Function
Authors: Oleszkiewicz Anna , Park Dahae , Resler Katarzyna , Draf Julia , Schulze Anja , Zang Yunpeng , Hähner Antje , Hummel Thomas 
Published: May 2019

Abstract
To date, most studies on the relationship between chemosensory performance and quality of life have focused on orthonasal measures of olfactory function. In the current investigation, we examined the predictive value of orthonasal and flavor identification indices of olfactory function on a wide spectrum of health and sociopsychological factors, including quality of life, life satisfaction, overall health, and depressive symptoms. Participants were 178 ENT patients (Mage = 58 ± 1), representing various causes of olfactory loss: idiopathic smell loss (n = 51; Mage = 63 ± 2), sinunasal disease (n = 27; Mage = 56 ± 3), head trauma (n = 33; Mage = 51 ± 2), and infections of the upper respiratory tract (n = 67; Mage = 59 ± 2). They completed self-report questionnaires and underwent olfactory testing using Sniffin’ Sticks (orthonasal olfactory testing) and “Taste Powder” (intraorally applied flavors for retronasal olfactory testing, additionally inducing taste sensation). Data were analyzed with hierarchical regression models wherein the first step included subjects’ sex, age, and orthonasal olfaction score. In the second step, we included the “Taste Powder” score. Tested models revealed that the first step was not significantly predicting variables of interest; however, there was an improvement of the model’s predictive value when the “Taste Powder” score was added. Results of this study suggest that flavor identification significantly improves predictions of health and sociopsychological functioning of ENT patients with various etiologies.
A Validated HPTLC Densitometric Method for Determination of Lupeol, β-Sitosterol and Rotenone in Tephrosia purpurea: A Seasonal Study
Authors: Khatoon Sayyada , Irshad Saba , Pandey Madan Mohan , Rastogi Subha , Rawat Ajay Kumar Singh 
Published: May 2019

Abstract
Tephrosia purpurea (L.) Pers., commonly known as “sarpunkha” and “wild indigo”, is being used in traditional systems of medicine to treat liver disorders, spleen and kidney. In the present study, a validated High Performance Thin Layer Chromatography (HPTLC) method was established for the estimation of lupeol, β-sitosterol and rotenone in various extracts of T. purpurea with the aim to see the effect of seasons on the quantity of aforesaid phytoconstituents. The plant material was collected in summer (April), rainy (August) and winter (December) during 2013–2014 from Lucknow, India. The method was validated in terms of precision, repeatability, specificity, sensitivity linearity and robustness. The method permits reliable quantification and showed good resolution on silica gel with toluene-ethyl acetate-formic acid (9:1:1 v/v/v) as mobile phase, and characteristic bands of β-sitosterol, rotenone and lupeol were observed at Rf 0.38, 0.45 and 0.52, respectively. The content of aforesaid phytoconstituents varies from season to season and extract to extract. Our finding indicated that winter season (December) may not be appropriate for collection of T. purpurea for the preparation of therapeutic formulations because of the high content of rotenone, a known insecticide that is responsible for Parkinson’s disease and associated with heart failure, fatty liver and liver necrosis.
Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam
Authors: Dong Huan V , Pham Loc Q , Nguyen Hoa T , Nguyen Minh X B , Nguyen Trung V , May Folasade , Le Giang M , Klausner Jeffrey D 
Published: May 2019

Abstract

Background
Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking.

Methods
Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups.

Results
Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1–4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P &lt; .05, all comparisons).

Conclusions
MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.
A curated collection of transcriptome datasets to investigate the molecular mechanisms of immunoglobulin E-mediated atopic diseases
Authors: Huang Susie S Y , Al Ali Fatima , Boughorbel Sabri , Toufiq Mohammed , Chaussabel Damien , Garand Mathieu 
Published: May 2019

Abstract
Prevalence of allergies has reached ~20% of population in developed countries and sensitization rate to one or more allergens among school age children are approaching 50%. However, the combination of the complexity of atopic allergy susceptibility/development and environmental factors has made identification of gene biomarkers challenging. The amount of publicly accessible transcriptomic data presents an unprecedented opportunity for mechanistic discoveries and validation of complex disease signatures across studies. However, this necessitates structured methodologies and visual tools for the interpretation of results. Here, we present a curated collection of transcriptomic datasets relevant to immunoglobin E-mediated atopic diseases (ranging from allergies to primary immunodeficiencies). Thirty-three datasets from the Gene Expression Omnibus, encompassing 1860 transcriptome profiles, were made available on the Gene Expression Browser (GXB), an online and open-source web application that allows for the query, visualization and annotation of metadata. The thematic compositions, disease categories, sample number and platforms of the collection are described. Ranked gene lists and sample grouping are used to facilitate data visualization/interpretation and are available online via GXB (http://ige.gxbsidra.org/dm3/geneBrowser/list). Dataset validation using associated publications showed good concordance in GXB gene expression trend and fold-change.
Age-related analysis of the gut microbiome in a purebred dog colony
Authors: Mizukami Keijiro , Uchiyama Jumpei , Igarashi Hirotaka , Murakami Hironobu , Osumi Takafumi , Shima Ayaka , Ishiahra Genki , Nasukawa Tadahiro , Une Yumi , Sakaguchi Masahiro 
Published: May 2019

ABSTRACT
Dogs are model animals that can be used to study the gut microbiome. Although the gut microbiome is assumed to be closely related to aging, information pertaining to this relationship in dogs is limited. Here, we examined the association between the canine gut microbiome and age via a bacterial 16S rRNA gene amplicon sequence analysis in a colony of 43 Japanese purebred Shiba Inu dogs. We found that microbial diversity tended to decrease with aging. A differential abundance analysis showed an association of a single specific microbe with aging. The age-related coabundance network analysis showed that two microbial network modules were positively and negatively associated with aging, respectively. These results suggest that the dog gut microbiome is likely to vary with aging.
A Category of Wide Subcategories
Authors: Buan Aslak Bakke , Marsh Bethany Rose 
Published: May 2019

Abstract
An algebra is said to be $\tau$-tilting finite provided it has only a finite number of $\tau$-rigid objects up to isomorphism. To each such algebra, we associate a category whose objects are the wide subcategories of its category of finite dimensional modules, and whose morphisms are indexed by support $\tau$-tilting pairs.
Multiple-Strain Infections of Human Cytomegalovirus With High Genomic Diversity Are Common in Breast Milk From Human Immunodeficiency Virus–Infected Women in Zambia
Authors: Suárez Nicolás M , Musonda Kunda G , Escriva Eric , Njenga Margaret , Agbueze Anthony , Camiolo Salvatore , Davison Andrew J , Gompels Ursula A 
Published: May 2019

Abstract

Background
In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, where multiple-strain infection appears linked to disease severity. The situation is less documented in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in human immunodeficiency virus (HIV)–infected women. We investigated HCMV strain diversity.

Methods
High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-infected and 7 HIV-negative) at 4–16 weeks postpartum, then analyzed by genome assembly and novel motif-based genotyping in 12 hypervariable HCMV genes.

Results
Among the 20 samples from 14 donors (13 HIV-infected and one HIV-negative) who yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to 5 strains per person were apparent in 9 HIV-infected women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus entry and immunomodulation, but not between genes more distant from each other.

Conclusions
Breast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.
Plasma Fibronectin Levels Identified via Quantitative Proteomics Profiling Predicts Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B
Authors: Liu Fen , Seto Wai-Kay , Wong Danny Ka-Ho , Huang Fung-Yu , Cheung Ka-Shing , Mak Lung-Yi , Sharma Rakesh , Zhang Saisai , Fung James , Lai Ching-Lung , Yuen Man-Fung 
Published: May 2019

Abstract

Background
Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined.

Methods
We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-positive controls. Plasma protein profiling was performed using isobaric tags for relative and absolute quantitation-based proteomics, with the expression of candidate proteins validated in a separate cohort. The predictive value of fibronectin was assessed at 3 years, 1 year (Year -1) before, and at the time (Year 0) of HBsAg seroclearance.

Results
Four hundred eighty-seven plasma proteins were identified via proteomics, with 97 proteins showing altered expression. In the verification cohort (n = 90), median plasma fibronectin levels in patients with HBsAg seroclearance was higher than in controls (P = .009). In the longitudinal cohort (n = 164), patients with HBsAg seroclearance, compared with controls, had a higher median fibronectin levels at Year -1 (413.26 vs 227.95 µg/mL) and Year 0 (349.45 vs 208.72 µg/mL) (both P < .001). In patients with an annual HBsAg log reduction >0.5, Year -1 fibronectin level achieved an area under the receiving operator characteristic of 0.884 in predicting HBsAg seroclearance.

Conclusions
Using proteomics-based technology, plasma fibronectin may be associated with HBsAg seroclearance and a potential predictor of “functional cure”.
Tracing the Legacy: China's Historical Aid and Contemporary Investment in Africa
Authors: Morgan Pippa , Zheng Yu 
Published: May 2019

Abstract
In this article we depart from the classic model of foreign direct investment (FDI) determinants and examine the effect of sociohistorical factors on FDI. We argue that past foreign aid projects confer social capital that constitutes specific resources available to investors in the present, increasing their preferences for host countries in which their home country has accumulated more social capital. We use new data on China's historical aid in Africa to test these contentions, uncovering a positive, significant connection between China's historical aid program in Africa (1956–1999) and contemporary (2000–2015) investments by Chinese companies. While China's historical aid may have been politically driven, it has had important long-term consequences for its commercial investors. More broadly, these findings suggest a sociohistorical explanation of the puzzle of why Chinese foreign investments deviate from conventional FDI patterns.
Hybrid bag of approaches to characterize selection criteria for cohort identification
Authors: Vydiswaran V G Vinod , Strayhorn Asher , Zhao Xinyan , Robinson Phil , Agarwal Mahesh , Bagazinski Erin , Essiet Madia , Iott Bradley E , Joo Hyeon , Ko PingJui , Lee Dahee , Lu Jin Xiu , Liu Jinghui , Murali Adharsh , Sasagawa Koki , Wang Tianshi , Yuan Nalingna 
Published: May 2019

Abstract

Objective
The 2018 National NLP Clinical Challenge (2018 n2c2) focused on the task of cohort selection for clinical trials, where participating systems were tasked with analyzing longitudinal patient records to determine if the patients met or did not meet any of the 13 selection criteria. This article describes our participation in this shared task.

Materials and Methods
We followed a hybrid approach combining pattern-based, knowledge-intensive, and feature weighting techniques. After preprocessing the notes using publicly available natural language processing tools, we developed individual criterion-specific components that relied on collecting knowledge resources relevant for these criteria and pattern-based and weighting approaches to identify “met” and “not met” cases.

Results
As part of the 2018 n2c2 challenge, 3 runs were submitted. The overall micro-averaged F1 on the training set was 0.9444. On the test set, the micro-averaged F1 for the 3 submitted runs were 0.9075, 0.9065, and 0.9056. The best run was placed second in the overall challenge and all 3 runs were statistically similar to the top-ranked system. A reimplemented system achieved the best overall F1 of 0.9111 on the test set.

Discussion
We highlight the need for a focused resource-intensive effort to address the class imbalance in the cohort selection identification task.

Conclusion
Our hybrid approach was able to identify all selection criteria with high F1 performance on both training and test sets. Based on our participation in the 2018 n2c2 task, we conclude that there is merit in continuing a focused criterion-specific analysis and developing appropriate knowledge resources to build a quality cohort selection system.