Predicting Medical Subject Headings Based on Abstract Similarity and Citations to MEDLINE Records

We describe a classifier-enhanced nearest neighbor approach to assigning Medical Subject Headings (MeSH) to unlabeled documents using a combination of abstract similarities and direct citations to labeled MEDLINE records. The approach frames the classification problem by decomposing it into sets of siblings in the MeSH hierarchy (e.g., training a classifier for predicting "Heterocyclic Compounds, 2-Ring" vs. other "Heterocyclic Compounds"). Preliminary experiments using a small but diverse set of MeSH terms shows the highest performance when using both abstracts and citations compared to each alone, and coupled with a non-naive classifier: 90+% precision and recall with 10-fold cross-validation. NLM's Medical Text Indexer (MTI) tool achieves similar overall performance but varies more across the terms tested. For example, MTI performs better on "Heterocyclic Compounds, 2-Ring", while our approach performs better on Alzheimer Disease and Neuroimaging. Our approach can be applied broadly to documents with abstracts that are similar to (or cite) MEDLINE abstracts, which would help linking and searching across bibliographic databases beyond MEDLINE.Ope

Low Bone Mineral Density in Inflammatory Bowel Disease

Low bone mineral density is a common and detrimental extra-intestinal complication in inflammatory bowel disease (IBO). There are several factors known to contribute to low bone mineral density in this population. The case outlined reviews a postmenopausal female with osteoporosis. While low bone mineral density in postmenopausal women is well-studied and often applied to 180, the process of bone loss is different in IBD which makes treatment more difficult. The literature review discusses the increased 1isk for low bone mineral density in IBD, factors increasing its risk, current screening and preventive care recommendations, barriers to improved bone mineral density in IBD, and future treatments. Although low bone mineral density is a well-known complication of IBD, its management is often neglected in patients with IBD. Screening, preventive care, and treatment of low bone mineral density remain poorly implemented among health care providers. There remains a need for additional studies to better understand the pathophysiology of low bone mineral density in IBD, improve screening and preventive care guidelines, and discover more successful treatment options An online literature search was conducted using the University of North Dakota\u27s Harley E. French Library of the Health Sciences to find literah1re addressing this topic. The database used in this search was PubMed. In the search, the Advanced Search Builder was used with keywords Inflammatory Bowel Disease AND osteoporosis which yielded 548 results. The limit of articles published in English was then applied which narrowed results to 467. The next filter applied allowed only results published within the past five years in order to include the most recent research. After this filter was applied, 122 results remained. The last filter applied narrowed down results with free full text available which left 42 articles. After reviewing these articles, twelve were relevant to the topic

Association of comorbidity burden with abnormal cardiac mechanics: Findings from the HyperGEN study

BACKGROUND: Comorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics. METHODS AND RESULTS: We performed speckle‐tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51±14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, β=−0.32 [95% CI −0.44, −0.20] per 1‐unit increase in number of comorbidities for global longitudinal strain; β=−0.16 [95% CI −0.20, −0.11] for e' velocity; P≤0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons). CONCLUSIONS: Higher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF

Impact of Common Variation in Bone-Related Genes on Type 2 Diabetes and Related Traits

Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r2 > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post–oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations

Struggles of Governance and Autonomy in the Field of Kulturskole

The Norwegian extracurricular schools of music and performing arts, kulturskolen, largely govern themselves. In contrast to other types of law obliged schools, kulturskolen receives no clear signals from either state levels, or municipality/county municipality levels, but rather are left to informal steering mechanisms on individual or collective levels. This leads to a wide diversity of what disciplines that are offered, what collaborations that are conducted, what aims, intentions, profiles, and competences that are managed, and thus to very different conditions for what the pupils might learn and experience. This article is a theoretical discussion of this finding, investigating diverse forms of conduct that are identified on (i) state, (ii) community, and (iii) individual school level. The article particularly looks at the identified steering mechanisms, with Michel Foucault’s thoughts of governmentality and power/knowledge as its basis. This discussion on how the kulturskole regulates itself is a contribution to the body of research about kulturskole, cultural policy, and about extracurricular arts education in the kulturskole that aims to be “for all.”

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin