Allelic based gene-gene interactions in rheumatoid arthritis

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel method that can detect the interaction by a definition of nonrandom association of alleles that occurs when the contribution to RA of a particular allele inherited in one gene depends on a particular allele inherited at other unlinked genes. Starting with 639 single-nucleotide polymorphisms (SNPs) from 26 candidate genes, we identified ten two-way interacting genes and one case of three-way interacting genes. SNP rs2476601 on PTPN22 interacts with rs2306772 on SLC22A4, which interacts with rs881372 on TRAF1 and rs2900180 on C5, respectively. SNP rs2900180 on C5 interacts with rs2242720 on RUNX1, which interacts with rs881375 on TRAF1. Furthermore, rs2476601 on PTPN22 also interacts with three SNPs (rs2905325, rs1476482, and rs2106549) in linkage disequilibrium (LD) on IL6. The other three SNPs (rs2961280, rs2961283, and rs2905308) in LD on IL6 interact with two SNPs (rs477515 and rs2516049) on HLA-DRB1. SNPs rs660895 and rs532098 on HLA-DRB1 interact with rs2834779 and four SNPs in LD on RUNX1. Three-way interacting genes of rs10229203 on IL6, rs4816502 on RUNX1, and rs10818500 on C5 were also detected

Risk factors for recurrent injuries in victims of suspected non-accidental trauma: a retrospective cohort study

BACKGROUND: Many children who are victims of non-accidental trauma (NAT) may be repeatedly evaluated for injuries related to maltreatment. The purpose of this study was to identify risk factors for repeated injuries in children with suspected NAT. METHODS: We conducted a retrospective cohort study using claims data from a pediatric Medicaid accountable care organization. Children with birth claims and at least one non-birth related claim indicating a diagnosis of NAT or skeletal survey in 2007–2011 were included. Recurrent events were defined as independent episodes of care involving an urgent/emergent care setting that included a diagnosis code specific for child abuse, a CPT code for a skeletal survey, or a diagnosis code for an injury suspicious for abuse. Cox proportional hazards models were used to examine risk factors for recurrent events. RESULTS: Of the 1,361 children with suspected NAT, a recurrent NAT event occurred in 26% within 1 year and 40% within 2 years of their initial event. Independent risk factors for a recurrent NAT event included a rural residence, age < 30 months old, having only 1 or 2 initially detected injuries, and having a dislocation, open wound, or superficial injury at the previous event (p ≤ 0.01 for all). CONCLUSIONS: Over 25% of children who experienced a suspected NAT event had a recurrent episode within one year. These children were younger and more likely to present with “minor” injuries at their previous event

Detecting Machine-obfuscated Plagiarism

Related dataset is at https://doi.org/10.7302/bewj-qx93 and also listed in the dc.relation field of the full item record.Research on academic integrity has identified online paraphrasing tools as a severe threat to the effectiveness of plagiarism detection systems. To enable the automated identification of machine-paraphrased text, we make three contributions. First, we evaluate the effectiveness of six prominent word embedding models in combination with five classifiers for distinguishing human-written from machine-paraphrased text. The best performing classification approach achieves an accuracy of 99.0% for documents and 83.4% for paragraphs. Second, we show that the best approach outperforms human experts and established plagiarism detection systems for these classification tasks. Third, we provide a Web application that uses the best performing classification approach to indicate whether a text underwent machine-paraphrasing. The data and code of our study are openly available.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152346/1/Foltynek2020_Paraphrase_Detection.pdfDescription of Foltynek2020_Paraphrase_Detection.pdf : Foltynek2020_Paraphrase_Detectio

The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care

Observational and Physical Classification of Supernovae

This chapter describes the current classification scheme of supernovae (SNe). This scheme has evolved over many decades and now includes numerous SN Types and sub-types. Many of these are universally recognized, while there are controversies regarding the definitions, membership and even the names of some sub-classes; we will try to review here the commonly-used nomenclature, noting the main variants when possible. SN Types are defined according to observational properties; mostly visible-light spectra near maximum light, as well as according to their photometric properties. However, a long-term goal of SN classification is to associate observationally-defined classes with specific physical explosive phenomena. We show here that this aspiration is now finally coming to fruition, and we establish the SN classification scheme upon direct observational evidence connecting SN groups with specific progenitor stars. Observationally, the broad class of Type II SNe contains objects showing strong spectroscopic signatures of hydrogen, while objects lacking such signatures are of Type I, which is further divided to numerous subclasses. Recently a class of super-luminous SNe (SLSNe, typically 10 times more luminous than standard events) has been identified, and it is discussed. We end this chapter by briefly describing a proposed alternative classification scheme that is inspired by the stellar classification system. This system presents our emerging physical understanding of SN explosions, while clearly separating robust observational properties from physical inferences that can be debated. This new system is quantitative, and naturally deals with events distributed along a continuum, rather than being strictly divided into discrete classes. Thus, it may be more suitable to the coming era where SN numbers will quickly expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most welcom

Iron Incorporation and Post-Malaria Anaemia

BACKGROUND: Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined the red blood cell incorporation of oral administered stable isotopes of iron and compared incorporation between age matched 18 to 36 months old children with either anaemia post-malaria (n = 37) or presumed iron deficiency anaemia alone (n = 36). All children were supplemented for 30 days with 2 mg/kg elemental iron as liquid iron sulphate and administered (57)Fe and (58)Fe on days 1 and 15 of supplementation respectively. (57)Fe and(58)Fe incorporation were significantly reduced (8% vs. 28%: p<0.001 and 14% vs. 26%: p = 0.045) in the malaria vs. non-malaria groups. There was a significantly greater haemoglobin response in the malaria group at both day 15 (p = 0.001) and 30 (p<0.000) with a regression analysis estimated greater change in haemoglobin of 7.2 g/l (s.e. 2.0) and 10.1 g/l (s.e. 2.5) respectively. CONCLUSION/SIGNIFICANCE: Post-malaria anaemia is associated with a better haemoglobin recovery despite a significant depressant effect on oral iron incorporation which may indicate that early erythropoetic iron need is met by iron recycling rather than oral iron. Supplemental iron administration is of questionable utility within 2 weeks of clinical malaria in children with mild or moderate anaemia

Risk Factors for Breast Cancer and Expression of Insulin-Like Growth Factor-2 (IGF-2) in Women with Breast Cancer in Wuhan City, China

PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue). RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016), working attributes (OR = 1.004, 95%CI = 1.002 = 1.006), long menstrual period (OR = 1.007, 95%CI = 1.005-1.009), high parity OR = 1.003, 95%CI = 1.001-1.005) , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005), family history of cancer (OR = 1.003, 95%CI = 1.000-1.005), period of night shift (OR = 1.003, 95%CI = 1.001-1.006), live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008), and family problems (OR = 1.010, 95%CI = 1.005-1.014) were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively). In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05). CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue)

The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish

A genomic atlas of systemic interindividual epigenetic variation in humans

BACKGROUND: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. RESULTS: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. CONCLUSIONS: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease

Simulating the carbon balance of a temperate larch forest under various meteorological conditions

<p>Abstract</p> <p>Background</p> <p>Changes in the timing of phenological events may cause the annual carbon budget of deciduous forests to change. Therefore, one should take such events into account when evaluating the effects of global warming on deciduous forests. In this article, we report on the results of numerical experiments done with a model that includes a phenological module simulating the timing of bud burst and other phenological events and estimating maximum leaf area index.</p> <p>Results</p> <p>This study suggests that the negative effects of warming on tree productivity (net primary production) outweigh the positive effects of a prolonged growing season. An increase in air temperature by 3°C (5°C) reduces cumulative net primary production by 21.3% (34.2%). Similarly, cumulative net ecosystem production (the difference between cumulative net primary production and heterotrophic respiration) decreases by 43.5% (64.5%) when temperatures are increased by 3°C (5°C). However, the positive effects of CO₂enrichment (2 × CO₂) outweigh the negative effects of warming (<5°C).</p> <p>Conclusion</p> <p>Although the model was calibrated and validated for a specific forest ecosystem, the implications of the study may be extrapolated to deciduous forests in cool-temperate zones. These forests share common features, and it can be conjectured that carbon stocks would increase in such forests in the face of doubled CO₂and increased temperatures as long as the increase in temperature does not exceed 5°C.</p