Performance of upper limb entry item to predict forced vital capacity in dysferlin-deficient limb girdle muscular dystrophy.

Dysferlin-deficient limb girdle muscular dystrophy (LGMD R2), also referred to as dysferlinopathy, can be associated with respiratory muscle weakness as the disease progresses. Clinical practice guidelines recommend biennial lung function assessments in patients with dysferlinopathy to screen for respiratory impairment. However, lack of universal access to spirometry equipment and trained specialists makes regular monitoring challenging.

Longitudinal Pilot Evaluation of the Gut Microbiota Comparing Patients With and Without Chronic Kidney Disease.

Objective: The gut microbiota contributes to metabolic diseases, such as diabetes and hypertension, but is poorly characterized in chronic kidney disease (CKD).

Design And Methods: We enrolled 24 adults within household pairs, in which at least one member had self-reported kidney disease, diabetes, or hypertension. CKD was classified based on estimated glomerular filtration rate < 60 mL/min/1.

Diversity of plant DNA in stool is linked to dietary quality, age, and household income.

Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast -P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Objective: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification.

Methods: A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months.

RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.

Objectives: Despite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored.

Materials And Methods: We identified differentially spliced genes (DSGs) and differentially expressed genes (DEGs) in biobanked lung squamous cell carcinoma (LUSC) between patients of West African and European ancestry, using ancestral genotyping and Affymetrix Clariom D array. DSGs and DEGs were validated independently using the National Cancer Institute Genomic Data Commons.

The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants.

Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types from The Cancer Genome Atlas (TCGA), revealing that species equiprevalent across sample types are predominantly contaminants, bearing unique signatures from each TCGA-designated sequencing center. Removing such species mitigated batch effects and isolated the tissue-resident microbiome, which was validated by original matched TCGA samples.

Short-Chain Fatty Acid Production by Gut Microbiota from Children with Obesity Differs According to Prebiotic Choice and Bacterial Community Composition.

Pediatric obesity remains a public health burden and continues to increase in prevalence. The gut microbiota plays a causal role in obesity and is a promising therapeutic target. Specifically, the microbial production of short-chain fatty acids (SCFA) from the fermentation of otherwise indigestible dietary carbohydrates may protect against pediatric obesity and metabolic syndrome.

Rationale and design of "Hearts & Parks": study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity.

Background: The prevalence of child and adolescent obesity and severe obesity continues to increase despite decades of policy and research aimed at prevention. Obesity strongly predicts cardiovascular and metabolic disease risk; both begin in childhood. Children who receive intensive behavioral interventions can reduce body mass index (BMI) and reverse disease risk.

Bridging the gaps: using an NHP model to predict single dose radiation absorption in humans.

Design and characterization of a radiation biodosimetry device are complicated by the fact that the requisite data are not available in the intended use population, namely humans exposed to a single, whole-body radiation dose. Instead, one must turn to model systems. We discuss our studies utilizing healthy, unexposed humans, human bone marrow transplant patients undergoing total body irradiation (TBI), non-human primates subjected to the same irradiation regimen received by the human TBI patients and NHPs given a single, whole-body dose of ionizing radiation.

Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling.

Abnormal feedback of serum calcium to parathyroid hormone (PTH) secretion is the hallmark of primary hyperparathyroidism (PHPT). Although the molecular pathogenesis of parathyroid neoplasia in PHPT has been linked to abnormal expression of genes involved in cell growth (e.g.

A Molecular Profile of the Endothelial Cell Response to Ionizing Radiation.

Ionizing radiation exposure can cause acute radiation sickness (ARS) by damaging the hematopoietic compartment. Radiation damages quiescent hematopoietic stem cells (HSCs) and proliferating hematopoietic cells, resulting in neutropenia, thrombocytopenia and increased risk for long-term hematopoietic dysfunction and myelodysplasia. While some aspects of the hematopoietic response to radiation injury are intrinsic to hematopoietic cells, the recovery of the HSC pool and overall hematopoiesis is also dependent on signals from bone marrow endothelial cells (BM ECs) within the HSC vascular niche.

Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.

Purpose: We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: (1) gene expression profiles are associated with DCE-MRI perfusion patterns, and (2) association between long-term overall survival data and gene expression profiles can lead to the identification of novel predictive biomarkers.

A translatable predictor of human radiation exposure.

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims.

Biological pathway selection through Bayesian integrative modeling.

Pathway analysis has become a central approach to understanding the underlying biology of differentially expressed genes. As large amounts of microarray data have been accumulated in public repositories, flexible methodologies are needed to extend the analysis of simple case-control studies in order to place them in context with the vast quantities of available and highly heterogeneous data sets. To address this challenge, we have developed a two-level model, consisting of 1) a joint Bayesian factor model that integrates multiple microarray experiments and ties each factor to a predefined pathway and 2) a point mass mixture distribution that infers which factors are relevant/irrelevant to each dataset.

A methodology for utilization of predictive genomic signatures in FFPE samples.

Background: Gene expression signatures developed to measure the activity of oncogenic signaling pathways have been used to dissect the heterogeneity of tumor samples and to predict sensitivity to various cancer drugs that target components of the relevant pathways, thus potentially identifying therapeutic options for subgroups of patients. To facilitate broad use, including in a clinical setting, the ability to generate data from formalin-fixed, paraffin-embedded (FFPE) tissues is essential.

Methods: Patterns of pathway activity in matched fresh-frozen and FFPE xenograft tumor samples were generated using the MessageAmp Premier methodology in combination with assays using Affymetrix arrays.

Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.

The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased expression of the calcium-sensing receptor (CaSR), a G protein-coupled receptor. However, CaSR expression is highly variable in parathyroid adenomas, and the lack of correlation between CaSR abundance and calcium-responsive PTH kinetics indicates that mechanisms independent of CaSR expression may contribute to aberrant calcium sensing in parathyroid disease.

Retraction: A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-80.

To the Editor: We would like to retract our article, "A Genomic Strategy to Refine Prognosis in Early-Stage Non-Small-Cell Lung Cancer,"(1) which was published in the Journal on August 10, 2006. Using a sample set from a study by the American College of Surgeons Oncology Group (ACOSOG) and a collection of samples from a study by the Cancer and Leukemia Group B (CALGB), we have tried and failed to reproduce results supporting the validation of the lung metagene model described in the article. We deeply regret the effect of this action on the work of other investigators.

Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.

In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB) can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI). However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals.

Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Purpose: Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clinical assays. The technical reproducibility of microarray platforms is well established. Here, we investigate the additional impact of intratumor heterogeneity, a largely unstudied component of variance, on the performance of several microarray-based assays in breast cancer.

Ovarian cancer tumor infiltrating T-regulatory (T(reg)) cells are associated with a metastatic phenotype.

Objective: The objective of this study was to examine the clinicopathologic correlates of T-regulatory (T(reg)) cell infiltration in serous ovarian cancers and to define gene signatures associated with high T(reg)s.

Methods: Tumor infiltrating T(reg) and cytotoxic T-cells (CTLs) were quantitated in 232 primary serous ovarian cancers by immunostaining for FOXP3 and CD8. Expression microarray analysis was performed in a subset of 48 advanced cancers with the highest and lowest numbers of infiltrating T(reg)s and a genomic signature was developed using binary regression.

Microarray analysis of early stage serous ovarian cancers shows profiles predictive of favorable outcome.

Purpose: Although few women with advanced serous ovarian cancer are cured, detection of the disease at an early stage is associated with a much higher likelihood of survival. We previously used gene expression array analysis to distinguish subsets of advanced cancers based on disease outcome. In the present study, we report on gene expression of early-stage cancers and validate our prognostic model for advanced-stage cancers.