bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying and ranking potential driver genes of Alzheimer’s disease using multiview evidence aggregation
Authors: Mukherjee Sumit , Perumal Thanneer M , Daily Kenneth , Sieberts Solveig K , Omberg Larsson , Preuss Christoph , Carter Gregory W , Mangravite Lara M , Logsdon Benjamin A 
Published: May 2019

Abstract

Motivation
Late onset Alzheimer’s disease is currently a disease with no known effective treatment options. To better understand disease, new multi-omic data-sets have recently been generated with the goal of identifying molecular causes of disease. However, most analytic studies using these datasets focus on uni-modal analysis of the data. Here, we propose a data driven approach to integrate multiple data types and analytic outcomes to aggregate evidences to support the hypothesis that a gene is a genetic driver of the disease. The main algorithmic contributions of our article are: (i) a general machine learning framework to learn the key characteristics of a few known driver genes from multiple feature sets and identifying other potential driver genes which have similar feature representations, and (ii) A flexible ranking scheme with the ability to integrate external validation in the form of Genome Wide Association Study summary statistics. While we currently focus on demonstrating the effectiveness of the approach using different analytic outcomes from RNA-Seq studies, this method is easily generalizable to other data modalities and analysis types.

Results
We demonstrate the utility of our machine learning algorithm on two benchmark multiview datasets by significantly outperforming the baseline approaches in predicting missing labels. We then use the algorithm to predict and rank potential drivers of Alzheimer’s. We show that our ranked genes show a significant enrichment for single nucleotide polymorphisms associated with Alzheimer’s and are enriched in pathways that have been previously associated with the disease.

Availability and implementation
Source code and link to all feature sets is available at https://github.com/Sage-Bionetworks/EvidenceAggregatedDriverRanking.
ARMBIS: accurate and robust matching of brain image sequences from multiple modal imaging techniques
Authors: Shen Qi , Xiao Goayu , Zheng Yingwei , Wang Jie , Liu Yue , Zhu Xutao , Jia Fan , Su Peng , Nie Binbin , Xu Fuqiang , Zhang Bin 
Published: May 2019

Abstract

Motivation
Study of brain images of rodent animals is the most straightforward way to understand brain functions and neural basis of physiological functions. An important step in brain image analysis is to precisely assign signal labels to specified brain regions through matching brain images to standardized brain reference atlases. However, no significant effort has been made to match different types of brain images to atlas images due to influence of artifact operation during slice preparation, relatively low resolution of images and large structural variations in individual brains.

Results
In this study, we develop a novel image sequence matching procedure, termed accurate and robust matching brain image sequences (ARMBIS), to match brain image sequences to established atlas image sequences. First, for a given query image sequence a scaling factor is estimated to match a reference image sequence by a curve fitting algorithm based on geometric features. Then, the texture features as well as the scale and rotation invariant shape features are extracted, and a dynamic programming-based procedure is designed to select optimal image subsequences. Finally, a hierarchical decision approach is employed to find the best matched subsequence using regional textures. Our simulation studies show that ARMBIS is effective and robust to image deformations such as linear or non-linear scaling, 2D or 3D rotations, tissue tear and tissue loss. We demonstrate the superior performance of ARMBIS on three types of brain images including magnetic resonance imaging, mCherry with 4′,6-diamidino-2-phenylindole (DAPI) staining and green fluorescent protein without DAPI staining images.

Availability and implementation
The R software package is freely available at https://www.synapse.org/#!Synapse:syn18638510/wiki/591054 for Not-For-Profit Institutions. If you are a For-Profit Institution, please contact the corresponding author.

Supplementary information
Supplementary data are available at Bioinformatics online.
The epigenetic impacts of endocrine disruptors on female reproduction across generations†
Authors: Rattan Saniya , Flaws Jodi A 
Published: May 2019

AbstractHumans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic dose responses that are atypical of standard toxicant exposures. The female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures.
Genetics of human female infertility†
Authors: Yatsenko Svetlana A , Rajkovic Aleksandar 
Published: May 2019

AbstractAbout 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.
Scientists' Warning on the Conservation of Subterranean Ecosystems
Authors: Mammola Stefano , Cardoso Pedro , Culver David C , Deharveng Louis , Ferreira Rodrigo L , Fišer Cene , Galassi Diana M P , Griebler Christian , Halse Stuart , Humphreys William F , Isaia Marco , Malard Florian , Martinez Alejandro , Moldovan Oana T , Niemiller Matthew L , Pavlek Martina , Reboleira Ana Sofia P S , Souza-Silva Marconi , Teeling Emma C , Wynne J Judson , Zagmajster Maja 
Published: May 2019

Abstract
In light of recent alarming trends in human population growth, climate change, and other environmental modifications, a “Warning to humanity” manifesto was published in BioScience in 2017. This call reiterated most of the ideas originally expressed by the Union of Concerned Scientists in 1992, including the fear that we are “pushing Earth's ecosystems beyond their capacities to support the web of life.” As subterranean biologists, we take this opportunity to emphasize the global importance and the conservation challenges associated with subterranean ecosystems. They likely represent the most widespread nonmarine environments on Earth, but specialized subterranean organisms remain among the least documented and studied. Largely overlooked in conservation policies, subterranean habitats play a critical role in the function of the web of life and provide important ecosystem services. We highlight the main threats to subterranean ecosystems and propose a set of effective actions to protect this globally important natural heritage.
Nakata index above 1500 mm2/m2 predicts death in absent pulmonary valve syndrome
Authors: Karaca-Altintas Yasemin , Laux Daniela , Gouton Marielle , Bensemlali Myriam , Roussin Régine , Hörer Jürgen , Raisky Olivier , Bonnet Damien 
Published: May 2019

AbstractOBJECTIVESAbsent pulmonary valve syndrome is a rare congenital heart disease with severe airway compression due to dilatation of the pulmonary arteries (PAs). We investigated risk factors for death and prolonged mechanical ventilation (&gt;7 days) and a threshold PA size for these outcomes.METHODSThis retrospective 2-centre cohort study included 68 patients with complete repair between January 1996 and December 2015.RESULTSMedian age at repair was 3.9 months (1.3–8.7 months), and median weight was 5 kg (4–7 kg). The mortality rate before hospital discharge was 12%, and the mortality rate at last follow-up was 19%. In multivariable analysis, risk factors for death were higher Nakata index [hazard ratio (HR) 1.001, 95% confidence interval (CI) 1.001–1.002; P &lt; 0.001] and lower SpO2 (HR 1.06, 95% CI 1.02–1.09; P = 0.002). The accuracy of the Nakata index to predict death was excellent (area under the curve at 6 months: 0.92; P = 0.010). A Nakata index above 1500 mm2/m2 predicted mortality at 6 months with a sensitivity of 98% and a specificity of 82%. Twenty-five patients (37%) had prolonged mechanical ventilation. The only multivariable risk factor for prolonged ventilation was lower weight at repair (odds ratio 2.9, 95% CI 1.3–6.7; P = 0.008). Neither PA plasty nor the LeCompte manoeuvre had a protective effect on mortality or prolonged ventilation. A Nakata index above 1500 mm2/m2 remained a risk factor for mortality (P = 0.022) in patients who had a PA plasty or the LeCompte manoeuvre.CONCLUSIONSIn patients with absent pulmonary valve syndrome, the Nakata index predicts mortality with a cut-off of 1500 mm2/m2. Lower weight at repair is the only multivariable risk factor for prolonged ventilation. Neither PA plasty nor the LeCompte manoeuvre had a protective effect on these outcomes.
The effectiveness of a professional development course: teachers’ perceptions
Authors: Sokel Frances 
Published: May 2019

Abstract
Although there has been increased interest in what constitutes effective professional development (PD) for in-service teachers in recent decades, the literature indicates that the issue continues to promote ongoing debate. Based upon the findings of previous research, this qualitative study set out to determine the extent to which, how, and why a PD course was considered effective in its contribution to the development and practice of the 28 in-service EFL teachers in Israel who participated in the course. Data from written reflective accounts, interviews, and field notes were collected and analysed. The findings identify various ways in which the course was considered effective, and reasons for such effectiveness, that, in turn, indicate the need for PD courses to be tailored to the current needs of practitioners as perceived by the course participants themselves.
Importance of EU regional support programmes for firm performance*
Authors: Beņkovskis Konstantīns , Tkačevs Oļegs , Yashiro Naomitsu 
Published: May 2019

Summary
This paper investigates the effects of EU regional support on firm productivity, the number of employees and other performance indicators. We use a rich firm-level dataset for Latvia – the country, where investment activities are largely affected by the availability of EU funding. After controlling for the fact that more productive and larger firms are more likely to acquire EU finds, we find that participation in projects co-financed by the European Regional Development Fund (ERDF) increases firms’ employment, turnover and capital stock per employee immediately, while it raises their productivity only two years after the launch of the projects. ERDF beneficiaries that are initially less productive, larger, less capital intensive and more financially leveraged enjoy larger productivity gains.
Multimorbidity and the Transition Out of Full-Time Paid Employment: A Longitudinal Analysis of the Health and Retirement Study
Authors: van Zon Sander K R , Reijneveld Sijmen A , Galaurchi Anne , Mendes de Leon Carlos F , Almansa Josué , Bültmann Ute 
Published: May 2019

Abstract

Objectives
This study aims to examine whether older workers aged 50–64 years with multimorbidity are at increased risk to transition from full-time paid employment to part-time employment, partial retirement, unemployment, disability, economic inactivity, full retirement or die than workers without a chronic health condition and workers with one chronic health condition, and whether socioeconomic position (SEP) modifies these transitions.

Method
Using data from the Health and Retirement Study (1992–2014; n = 10,719), sub-distribution hazard ratios with 95% confidence intervals were calculated with a time-varying Fine and Gray competing-risks survival regression model to examine exit from full-time paid employment. We investigated the modifying effect of SEP by examining its interaction with multimorbidity.

Results
Workers with multimorbidity had a higher risk of transitioning to partial retirement (1.45; 1.22, 1.72), disability (1.84; 1.21, 2.78) and full retirement (1.63; 1.47, 1.81), and they had a higher mortality risk (2.58; 1.71, 3.88) than workers without chronic disorders. Compared to workers with one chronic health condition, workers with multimorbidity had an increased risk for partial (1.19; 1.02, 1.40) and full retirement (1.29; 1.17, 1.42), and mortality (1.49; 1.09, 2.04). Only SEP measured as educational level modified the relationship between multimorbidity and mortality.

Discussion
Workers with multimorbidity seem more prone to leave full-time paid employment than workers without or with one a chronic health condition. Personalized work accommodations may be necessary to help workers with multimorbidity prolong their working life.
Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State
Authors: Diab Joseph , Hansen Terkel , Goll Rasmus , Stenlund Hans , Ahnlund Maria , Jensen Einar , Moritz Thomas , Florholmen Jon , Forsdahl Guro 
Published: May 2019

ABSTRACTBackgroundThe onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects.MethodsTreatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified.ResultsThe relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups.ConclusionThis study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.
Cmtm7 knockout inhibits B-1a cell development at the transitional (TrB-1a) stage
Authors: Liu Zhengyang , Liu Yuan , Li Ting , Wang Pingzhang , Mo Xiaoning , Lv Ping , Ge Qing , Ma Dalong , Han Wenling 
Published: May 2019

Abstract
Innate-like B-1a cells are an important cell population for production of natural IgM and interleukin-10 (IL-10), and act as the first line against pathogens. We determined that CMTM7 is essential for B-1a cell development. Following Cmtm7 (CKLF-like MARVEL transmembrane domain-containing 7) knockout, B-1a cell numbers decreased markedly in all investigated tissues. Using a bone marrow and fetal liver adoptive transfer model and conditional knockout mice, we showed that the reduction of B-1a cells resulted from B-cell-intrinsic defects. Because of B-1a cell loss, Cmtm7-deficient mice produced less IgM and IL-10, and were more susceptible to microbial sepsis. Self-renewal and homeostasis of mature B-1a cells in Cmtm7−/− mice were not impaired, suggesting the effect of Cmtm7 on B-1a cell development. Further investigations demonstrated that the function of Cmtm7 in B-1a cell development occurred at the specific transitional B-1a (TrB-1a) stage. Cmtm7 deficiency resulted in a slow proliferation and high cell death rate of TrB-1a cells. Thus, Cmtm7 controls B-1a cell development at the transitional stage.
Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing
Authors: Alghamdi Wael A , Antwi Sampson , Enimil Anthony , Yang Hongmei , Dompreh Albert , Wiesner Lubbe , Langaee Taimour , Peloquin Charles A , Kwara Awewura 
Published: May 2019

Abstract

Objectives
The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling.

Methods
This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12).

Results
One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only.

Conclusions
Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.
A Case-Control Study to Add Volumetric or Clinical Mammographic Density into the Tyrer-Cuzick Breast Cancer Risk Model
Authors: Brentnall Adam R , Cohn Wendy F , Knaus William A , Yaffe Martin J , Cuzick Jack , Harvey Jennifer A 
Published: May 2019

Abstract

Background
Accurate breast cancer risk assessment for women attending routine screening is needed to guide screening and preventive interventions. We evaluated the accuracy of risk predictions from both visual and volumetric mammographic density combined with the Tyrer-Cuzick breast cancer risk model.

Methods
A case-control study (474 patient participants and 2243 healthy control participants) of women aged 40–79 years was performed using self-reported classical risk factors. Breast density was measured by using automated volumetric software and Breast Imaging and Reporting Data System (BI-RADS) density categories. Odds ratios (95% CI) were estimated by using logistic regression, adjusted for age, demographic factors, and 10-year risk from the Tyrer-Cuzick model, for a change from the 25th to 75th percentile of the adjusted percent density distribution in control participants (IQ-OR).

Results
After adjustment for classical risk factors in the Tyrer-Cuzick model, age, and body mass index (BMI), BI-RADS density had an IQ-OR of 1.55 (95% CI = 1.33 to 1.80) compared with 1.40 (95% CI = 1.21 to 1.60) for volumetric percent density. Fibroglandular volume (IQ-OR = 1.28, 95% CI = 1.12 to 1.47) was a weaker predictor than was BI-RADS density (Pdiff = 0.014) or volumetric percent density (Pdiff = 0.065). In this setting, 4.8% of women were at high risk (8% + 10-year risk), using the Tyrer-Cuzick model without density, and 7.1% (BI-RADS) compared with 6.8% (volumetric) when combined with density.

Conclusion
The addition of volumetric and visual mammographic density measures to classical risk factors improves risk stratification. A combined risk could be used to guide precision medicine, through risk-adapted screening and prevention strategies.
The Fall of a Giant. Chemical evolution of Enceladus, alias the Gaia Sausage
Authors: Vincenzo Fiorenzo , Spitoni Emanuele , Calura Francesco , Matteucci Francesca , Silva Aguirre Victor , Miglio Andrea , Cescutti Gabriele 
Published: May 2019

ABSTRACT
We present the first chemical evolution model for Enceladus, alias the Gaia Sausage, to investigate the star formation history of one of the most massive satellites accreted by the Milky Way during a major merger event. Our best chemical evolution model for Enceladus nicely fits the observed stellar [α/Fe]–[Fe/H] chemical abundance trends, and reproduces the observed stellar metallicity distribution function, by assuming low star formation efficiency, fast infall time-scale, and mild outflow intensity. We predict a median age for Enceladus stars $12.33^{+0.92}_{-1.36}$ Gyr, and – at the time of the merger with our Galaxy (≈10 Gyr ago from Helmi et al.) – we predict for Enceladus a total stellar mass M⋆ ≈ 5 × 109 M$\odot$. By looking at the predictions of our best model, we discuss that merger events between the Galaxy and systems like Enceladus may have inhibited the gas accretion on to the Galaxy disc at high redshifts, heating up the gas in the halo. This scenario could explain the extended period of quenching in the star formation activity of our Galaxy about 10 Gyr ago, which is predicted by Milky Way chemical evolution models, in order to reproduce the observed bimodality in [α/Fe]–[Fe/H] between thick- and thin-disc stars.