Cardiac Manifestations of Lyme Disease.

Lyme carditis is an uncommon manifestation of Lyme disease. Most cases present with heart block of varying degrees, but the spectrum of disease includes other transient arrhythmias and structural manifestations, such as myopericarditis or cardiomyopathy. Antibiotics hasten the resolution of Lyme carditis, and cardiac pacing can be an adjunctive therapy.

Lyme Carditis in Hospitalized Children and Adults, a Case Series.

Background: Lyme carditis is an uncommon manifestation of Lyme disease. This report compares Lyme carditis presentation, management, and outcomes in pediatric and adult populations.

Methods: Charts of pediatric and adult patients with heart block (PR interval >300 ms) and positive Lyme serologies hospitalized in Portland, Maine, between January 2010 and December 2018 were analyzed.

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs.

Cancer is the leading cause of death in dogs, in part because many cases are identified at an advanced stage when clinical signs have developed, and prognosis is poor. Increased understanding of cancer as a disease of the genome has led to the introduction of liquid biopsy testing, allowing for detection of genomic alterations in cell-free DNA fragments in blood to facilitate earlier detection, characterization, and management of cancer through non-invasive means. Recent discoveries in the areas of genomics and oncology have provided a deeper understanding of the molecular origins and evolution of cancer, and of the "one health" similarities between humans and dogs that underlie the field of comparative oncology.

Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California.

Background: Bedaquiline (BDQ) is recommended for the treatment of multidrug-resistant tuberculosis (MDR TB), however, it has the potential to prolong QTc interval. We assessed the frequency and severity of QTc prolongation in patients receiving BDQ in California.

Methods: Based on chart review for patients receiving BDQ as part of MDR TB therapy from January 2013-May 2019, we analyzed QTc values at six pre-specified time points during BDQ therapy (baseline, 2, 4, 8, 12, and 24 weeks), as well as peak QTc, time to peak QTc, and the clinical characteristics of patients who had QTc elevation >500 milliseconds (ms) during therapy.

Development and Validation of an Ultradeep Next-Generation Sequencing Assay for Testing of Plasma Cell-Free DNA from Patients with Advanced Cancer.

Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy.

Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.

The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture.

High density DNA methylation array with single CpG site resolution.

We have developed a new generation of genome-wide DNA methylation BeadChip which allows high-throughput methylation profiling of the human genome. The new high density BeadChip can assay over 480K CpG sites and analyze twelve samples in parallel. The innovative content includes coverage of 99% of RefSeq genes with multiple probes per gene, 96% of CpG islands from the UCSC database, CpG island shores and additional content selected from whole-genome bisulfite sequencing data and input from DNA methylation experts.

Strengthening and neuromuscular reeducation of the gluteus maximus in a triathlete with exercise-associated cramping of the hamstrings.

Study Design: Case report.

Objective: To highlight the effects of an intervention program consisting of strengthening and neuromuscular reeducation of the gluteus maximus in an elite triathlete with exercise-associated muscle cramping (EAMC).

Background: Researchers have described 2 theories concerning the etiology of EAMC: (1) muscle fatigue and (2) electrolyte deficit.

Genome-wide DNA methylation profiling using Infinium® assay.

Aims: Bisulfite sequence analysis of individual CpG sites within genomic DNA is a powerful approach for methylation analysis in the genome. The major limitation of bisulfite-based methods is parallelization. Both array and next-generation sequencing technology are capable of addressing this bottleneck.

Medium- to high-throughput SNP genotyping using VeraCode microbeads.

Recent breakthroughs in multiplexed SNP (single nucleotide polymorphism) genotyping technology have enabled global mapping of the relationships between genetic variation and disease. Discoveries made by such whole-genome association studies often spur further interest in surveying more focused subsets of SNPs for validation or research purposes. Here we describe a new SNP genotyping platform that is flexible in assay content and multiplexing (up to 384 analytes), and can serve medium- to high-throughput applications.

Power to detect risk alleles using genome-wide tag SNP panels.

Advances in high-throughput genotyping and the International HapMap Project have enabled association studies at the whole-genome level. We have constructed whole-genome genotyping panels of over 550,000 (HumanHap550) and 650,000 (HumanHap650Y) SNP loci by choosing tag SNPs from all populations genotyped by the International HapMap Project. These panels also contain additional SNP content in regions that have historically been overrepresented in diseases, such as nonsynonymous sites, the MHC region, copy number variant regions and mitochondrial DNA.

Whole-genome genotyping.

We have developed an array-based whole-genome genotyping (WGG) assay (Infinium) using our BeadChip platform that effectively enables unlimited multiplexing and unconstrained single nucleotide polymorphism (SNP) selection. A single tube whole-genome amplification reaction is used to amplify the genome, and loci of interest are captured by specific hybridization of amplified gDNA to 50-mer probe arrays. After target capture, SNPs are genotyped on the array by a primer extension reaction in the presence of hapten-labeled nucleotides.

Illumina universal bead arrays.

This chapter describes an accurate, scalable, and flexible microarray technology. It includes a miniaturized array platform where each individual feature is quality controlled and a versatile assay that can be adapted for various genetic analyses, such as single nucleotide polymorphism genotyping, DNA methylation detection, and gene expression profiling. This chapter describes the concept of the BeadArray technology, two different Array of Arrays formats, the assay scheme and protocol, the performance of the system, and its use in large-scale genetic, epigenetic, and expression studies.

High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping.

Array-CGH is a powerful tool for the detection of chromosomal aberrations. The introduction of high-density SNP genotyping technology to genomic profiling, termed SNP-CGH, represents a further advance, since simultaneous measurement of both signal intensity variations and changes in allelic composition makes it possible to detect both copy number changes and copy-neutral loss-of-heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP loci, to detect chromosomal aberrations in samples bearing constitutional aberrations as well tumor samples at sub-100 kb effective resolution.

Whole-genome genotyping of haplotype tag single nucleotide polymorphisms.

The International HapMap Consortium recently completed genotyping over 3.8 million single nucleotide polymorphisms (SNPs) in three major populations, and the results of studying patterns of linkage disequilibrium indicate that characterization of 300,000-500,000 tag SNPs is sufficient to provide good genomic coverage for linkage-disequilibrium-based association studies in many populations. These whole-genome association studies will be used to dissect the genetics of complex diseases and pharmacogenomic drug responses.

Whole-genome genotyping with the single-base extension assay.

We describe an efficient, accurate and robust whole-genome genotyping (WGG) assay based on a two-color, single-base extension (SBE), single-nucleotide polymorphism (SNP)-scoring step. We report genotyping results for biallelic International HapMap quality control (QC) SNPs using a single probe per locus. We show scalability, throughput and accuracy of the system by resequencing homozygous loci from our 100k Human-1 Genotyping BeadChip.

High-throughput SNP genotyping on universal bead arrays.

We have developed a flexible, accurate and highly multiplexed SNP genotyping assay for high-throughput genetic analysis of large populations on a bead array platform. The novel genotyping system combines high assay conversion rate and data quality with >1500 multiplexing, and Array of Arrays formats. Genotyping assay oligos corresponding to specific SNP sequences are each linked to a unique sequence (address) that can hybridize to its complementary strand on universal arrays.

A highly informative SNP linkage panel for human genetic studies.

We have developed a highly informative set of single-nucleotide polymorphism (SNP) assays designed for linkage mapping of the human genome. These assays were developed on a robust multiplexed assay system to provide a combination of very high accuracy and data completeness with high throughput for linkage studies. The linkage panel is comprised of approximately 4,700 SNPs with 0.

Two methods of whole-genome amplification enable accurate genotyping across a 2320-SNP linkage panel.

Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.

A versatile assay for high-throughput gene expression profiling on universal array matrices.

We report a flexible, sensitive, and quantitative gene-expression profiling system for assaying more than 400 genes, with three probes per gene, for 96 samples in parallel. The cDNA-mediated annealing, selection, extension and ligation (DASL) assay targets specific transcripts, using oligonucleotides containing unique address sequences that can hybridize to universal arrays. Cell-specific gene expression profiles were obtained using this assay for hormone-treated cell lines and laser-capture microdissected cancer tissues.

A draft sequence of the rice genome (Oryza sativa L. ssp. japonica).

The genome of the japonica subspecies of rice, an important cereal and model monocot, was sequenced and assembled by whole-genome shotgun sequencing. The assembled sequence covers 93% of the 420-megabase genome. Gene predictions on the assembled sequence suggest that the genome contains 32,000 to 50,000 genes.

Design, synthesis, and evaluation of opioid analogues with non-peptidic beta-turn scaffold: enkephalin and endomorphin mimetics.

We have identified a mu-selective opioid receptor agonist without a cationic amino group in the molecule from libraries of bicyclic beta-turn peptidomimetics. The biologically active conformation of the lead is proposed to mimic an endomorphin type III 4 --> 1 beta-turn conformation.