Proteins in scalp hair of preschool children.

Background: (1)Early childhood experiences have long-lasting effects on subsequent mental and physical health, education, and employment. Measurement of these effects relies on insensitive behavioral signs, subjective assessments by adult observers, neuroimaging or neurophysiological studies, or retrospective epidemiologic outcomes. Despite intensive search, the underlying mechanisms for these long-term changes in development and health status remain unknown.

International Medical Graduate Physician Deaths From COVID-19 in the United States.

This case series study examines mortality rates due to COVID-19 among all physicians and international medical graduate physicians in the US.

Semantic Changepoint Detection for Finding Potentially Novel Research Publications.

How has the focus of research papers on a given disease changed over time? Identifying the papers at the cusps of change can help highlight the emergence of a new topic or a change in the direction of research. We present a generally applicable unsupervised approach to this question based on semantic changepoints within a given collection of research papers. We illustrate the approach by a range of examples based on a nascent corpus of literature on COVID-19 as well as subsets of papers from PubMed on the World Health Organization list of neglected tropical diseases.

Exposure to NO, CO, and PM is linked to regional DNA methylation differences in asthma.

Background: DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation ( and ) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites.

Erratum: Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, , from whole-genome sequences.

[This corrects the article DOI: 10.1038/npjgenmed.2015.

Automated Prediction of Hepatic Arterial Stenosis.

Several thousand life-saving liver transplants are performed each year. One of the most common causes of early transplant failure is arterial stenosis of the anastomotic junction. Early detection of transplant arterial stenosis can help prevent transplant failure and the need to re-transplant.

Engineered Tissue Inhibitor of Metalloproteinases-3 Variants Resistant to Endocytosis Have Prolonged Chondroprotective Activity.

Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a central inhibitor of matrix-degrading and sheddase families of metalloproteinases. Extracellular levels of the inhibitor are regulated by the balance between its retention on the extracellular matrix and its endocytic clearance by the scavenger receptor low density lipoprotein receptor-related protein 1 (LRP1). Here, we used molecular modeling to predict TIMP-3 residues potentially involved in binding to LRP1 based on the proposed LRP1 binding motif of 2 lysine residues separated by about 21 Å and mutated the candidate lysine residues to alanine individually and in pairs.

Association of tree nut and coconut sensitizations.

Background: Coconut (Cocos nucifera), despite being a drupe, was added to the US Food and Drug Administration list of tree nuts in 2006, causing potential confusion regarding the prevalence of coconut allergy among tree nut allergic patients.

Objective: To determine whether sensitization to tree nuts is associated with increased odds of coconut sensitization.

Methods: A single-center retrospective analysis of serum specific IgE levels to coconut, tree nuts (almond, Brazil nut, cashew, chestnut, hazelnut, macadamia, pecan, pistachio, and walnut), and controls (milk and peanut) was performed using deidentified data from January 2000 to August 2012.

Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, , from whole-genome sequences.

An important component of precision medicine-the use of whole-genome sequencing (WGS) to guide lifelong healthcare-is electronic decision support to inform drug choice and dosing. To achieve this, automated identification of genetic variation in genes involved in drug absorption, distribution, metabolism, excretion and response (ADMER) is required. is a major enzyme for drug bioactivation and elimination.

Drug repositioning using disease associated biological processes and network analysis of drug targets.

The analysis of disease using protein-protein interaction networks and network pharmacology has enabled better understanding of disease etiology and drug action. New insights into disease etiology and a better understanding of biological subsystems have opened up the possibility of finding new uses for existing drugs besides their original medical indication. We present an approach which makes use of the biological processes associated with diseases along with their known drugs and drug targets to predict Biological Process-Drug relationships.

Finding disease similarity based on implicit semantic similarity.

Genomics has contributed to a growing collection of gene-function and gene-disease annotations that can be exploited by informatics to study similarity between diseases. This can yield insight into disease etiology, reveal common pathophysiology and/or suggest treatment that can be appropriated from one disease to another. Estimating disease similarity solely on the basis of shared genes can be misleading as variable combinations of genes may be associated with similar diseases, especially for complex diseases.

Automated ontological gene annotation for computing disease similarity.

The annotation of gene/gene products with information on associated diseases is useful as an aid to clinical diagnosis and drug discovery. Several supervised and unsupervised methods exist that automate the association of genes with diseases, but relatively little work has been done to map protein sequence data to disease terminologies. This paper augments an existing open-disease terminology, the Disease Ontology (DO), and uses it for automated annotation of Swissprot records.

MindTrial: An Intelligent System for Clinical Trials.

The recruitment of human subjects for clinical trials research is a critically important step in the discovery of new cures for diseases. However, the current recruitment methodologies are inherently inefficient. Considerable resources are expended in efforts to recruit adequate numbers of patient volunteers who meet the inclusion/exclusion criteria for clinical trials.

A pragmatic approach to mapping the open biomedical ontologies.

There has been a large increase in the number of ontologies that have been introduced by the biomedical community in recent years. To maximise their potential, there is an urgent need for a mechanism to build interoperability between ontologies developed by different groups. While identifying and linking related concepts is of obvious importance, it is also essential to analyse how ontologies as a whole overlap and can be clustered.

Applications of medical informatics in allergy/immunology.

Objective: To provide a general overview of informatics and its interface with allergy/immunology.

Data Sources: The PubMed interface to MEDLINE was searched with the keywords asthma, allergy, or immunology together with the keywords informatics, bioinformatics, and information technology to retrieve the articles relevant to this review.

Study Selection: The authors' knowledge of the field was used to include sources of information other than those obtained through the MEDLINE search.

Ontological modeling of transformation in heart defect diagrams.

The accurate portrayal of a large volume data of variable heart defects is crucial to providing good patient care in pediatric cardiology. Our research aims to span the universe of congenital heart defects by generating illustrative diagrams that enhance data interpretation. To accommodate the range and severity of defects to be represented, we base our diagrams on transformation models applied to a normal heart rather than a static set of defects.

MachineProse: an ontological framework for scientific assertions.

Objective: The idea of testing a hypothesis is central to the practice of biomedical research. However, the results of testing a hypothesis are published mainly in the form of prose articles. Encoding the results as scientific assertions that are both human and machine readable would greatly enhance the synergistic growth and dissemination of knowledge.

Tandem machine learning for the identification of genes regulated by transcription factors.

Background: The identification of promoter regions that are regulated by a given transcription factor has traditionally relied upon the identification and distributions of binding sites recognized by the factor. In this study, we have developed a tandem machine learning approach for the identification of regulatory target genes based on these parameters and on the corresponding binding site information contents that measure the affinities of the factor for these cognate elements.

Results: This method has been validated using models of DNA binding sites recognized by the xenobiotic-sensitive nuclear receptor, PXR/RXRalpha, for target genes within the human genome.

An informatics search for the low-molecular weight chromium-binding peptide.

BACKGROUND: The amino acid composition of a low molecular weight chromium binding peptide (LMWCr), isolated from bovine liver, is reportedly E:G:C:D::4:2:2:2, though its sequence has not been discovered. There is some controversy surrounding the exact biochemical forms and the action of Cr(III) in biological systems; the topic has been the subject of many experimental reports and continues to be investigated. Clarification of Cr-protein interactions will further understanding Cr(III) biochemistry and provide a basis for novel therapies based on metallocomplexes or small molecules.

Collagenase unwinds triple-helical collagen prior to peptide bond hydrolysis.

Breakdown of triple-helical interstitial collagens is essential in embryonic development, organ morphogenesis and tissue remodelling and repair. Aberrant collagenolysis may result in diseases such as arthritis, cancer, atherosclerosis, aneurysm and fibrosis. In vertebrates, it is initiated by collagenases belonging to the matrix metalloproteinase (MMP) family.