RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial: Study rationale and design.

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful.

Race Differences in Interventions and Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010 to 2014.

Background Following the implementation of the HeartRescue project, with interventions in the community, emergency medical services, and hospitals to improve care and outcomes for out-of-hospital cardiac arrests (OHCA) in North Carolina, improved bystander and first responder treatments as well as survival were observed. This study aimed to determine whether these improvements were consistent across Black versus White individuals. Methods and Results Using the Cardiac Arrest Registry to Enhance Survival (CARES), we identified OHCA from 16 counties in North Carolina (population 3 million) from 2010 to 2014.

Structural and functional diversity among Type III restriction-modification systems that confer host DNA protection via methylation of the N4 atom of cytosine.

We report a new subgroup of Type III Restriction-Modification systems that use m4C methylation for host protection. Recognition specificities for six such systems, each recognizing a novel motif, have been determined using single molecule real-time DNA sequencing. In contrast to all previously characterized Type III systems which modify adenine to m6A, protective methylation of the host genome in these new systems is achieved by the N4-methylation of a cytosine base in one strand of an asymmetric 4 to 6 base pair recognition motif.

Nearly Complete Genome Sequence of Brugia malayi Strain FR3.

Lymphatic filariasis affects ∼120 million people and can result in elephantiasis and hydrocele. Here, we report the nearly complete genome sequence of the best-studied causative agent of lymphatic filariasis, The assembly contains four autosomes, an X chromosome, and only eight gaps but lacks a contiguous sequence for the known Y chromosome.

Care and outcomes of urban and non-urban out-of-hospital cardiac arrest patients during the HeartRescue Project in Washington state and North Carolina.

Aim: We examined overall and temporal differences in out-of-hospital cardiac arrest (OHCA) care and outcomes by urban versus non-urban setting separately for North Carolina (NC) and Washington State (WA) during HeartRescue initiatives and associations of urban/non-urban settings with outcome by state.

Methods: OHCAs of presumed cardiac etiology from counties with complete registry enrollment in NC during 2010-2014 (catchment population = 3,143,809) and WA during 2011-2014 (catchment population = 3,653,506) were identified. Geospatial arrest location data and US Census classification were used to categorize urban areas with ≥50,000 versus non-urban <50,000 people.

Sex chromosome evolution in parasitic nematodes of humans.

Sex determination mechanisms often differ even between related species yet the evolution of sex chromosomes remains poorly understood in all but a few model organisms. Some nematodes such as Caenorhabditis elegans have an XO sex determination system while others, such as the filarial parasite Brugia malayi, have an XY mechanism. We present a complete B.

Correction: Pulse-Field capillary electrophoresis of repeat-primed PCR amplicons for analysis of large repeats in Spinocerebellar Ataxia Type 10.

[This corrects the article DOI: 10.1371/journal.pone.

Pulse-Field capillary electrophoresis of repeat-primed PCR amplicons for analysis of large repeats in Spinocerebellar Ataxia Type 10.

Large expansions of microsatellite DNA cause several neurological diseases. In Spinocerebellar ataxia type 10 (SCA10), the repeat interruptions change disease phenotype; an (ATTCC)n or a (ATCCT)n/(ATCCC)n interruption within the (ATTCT)n repeat is associated with the robust phenotype of ataxia and epilepsy while mostly pure (ATTCT)n may have reduced penetrance. Large repeat expansions of SCA10, and many other microsatellite expansions, can exceed 10,000 base pairs (bp) in size.

CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.

Purpose: To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1).

Methods: We applied an amplification-free method, utilizing the CRISPR/Cas9 system, in combination with PacBio single-molecule real-time (SMRT) long-read sequencing, to study CTG18.

Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis Clinics.

Background: Out-of-hospital cardiac arrest, the leading cause of death among patients on hemodialysis, occurs frequently within outpatient dialysis centers. Practice guidelines recommend resuscitation training for all dialysis clinic staff and on-site defibrillator availability, but the extent of staff involvement in cardiopulmonary resuscitation (CPR) efforts and its association with outcomes is unknown.

Methods: We used data from the Cardiac Arrest Registry to Enhance Survival and the Centers for Medicare & Medicaid Services dialysis facility database to identify patients who had cardiac arrest within outpatient dialysis clinics between 2010 and 2016 in the southeastern United States.

Association Between Driving Distance From Nearest Fire Station and Survival of Out-of-Hospital Cardiac Arrest.

Background Firefighter first responders dispatched in parallel with emergency medical services ( EMS ) personnel for out-of-hospital cardiac arrests ( OHCA ) can provide early defibrillation to improve survival. We examined whether survival following first responder defibrillation differed according to driving distance from nearest fire station to OHCA site. Methods and Results From the CARES (Cardiac Arrest Registry to Enhance Survival) registry, we identified non- EMS witnessed OHCA s of presumed cardiac cause from 2010 to 2014 in Durham, Mecklenburg, and Wake counties, North Carolina.

Association of Bystander and First-Responder Efforts and Outcomes According to Sex: Results From the North Carolina HeartRescue Statewide Quality Improvement Initiative.

Background The Institute of Medicine has called for actions to understand and target sex-related differences in care and outcomes for out-of-hospital cardiac arrest patients. We assessed changes in bystander and first-responder interventions and outcomes for males versus females after statewide efforts to improve cardiac arrest care. Methods and Results We identified out-of-hospital cardiac arrests from North Carolina (2010-2014) through the CARES (Cardiac Arrest Registry to Enhance Survival) registry.

SMRT-Cappable-seq reveals complex operon variants in bacteria.

Current methods for genome-wide analysis of gene expression require fragmentation of original transcripts into small fragments for short-read sequencing. In bacteria, the resulting fragmented information hides operon complexity. Additionally, in vivo processing of transcripts confounds the accurate identification of the 5' and 3' ends of operons.

Detailed analysis of HTT repeat elements in human blood using targeted amplification-free long-read sequencing.

Amplification of DNA is required as a mandatory step during library preparation in most targeted sequencing protocols. This can be a critical limitation when targeting regions that are highly repetitive or with extreme guanine-cytosine (GC) content, including repeat expansions associated with human disease. Here, we used an amplification-free protocol for targeted enrichment utilizing the CRISPR/Cas9 system (No-Amp Targeted sequencing) in combination with single molecule, real-time (SMRT) sequencing for studying repeat elements in the huntingtin (HTT) gene, where an expanded CAG repeat is causative for Huntington disease.

Universal Alternative Splicing of Noncoding Exons.

The human transcriptome is so large, diverse, and dynamic that, even after a decade of investigation by RNA sequencing (RNA-seq), we have yet to resolve its true dimensions. RNA-seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read RNA-seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution.

Methylomic and phenotypic analysis of the ModH5 phasevarion of Helicobacter pylori.

The Helicobacter pylori phase variable gene modH, typified by gene HP1522 in strain 26695, encodes a N-adenosine type III DNA methyltransferase. Our previous studies identified multiple strain-specific modH variants (modH1 - modH19) and showed that phase variation of modH5 in H. pylori P12 influenced expression of motility-associated genes and outer membrane protein gene hopG.

Association of Public Health Initiatives With Outcomes for Out-of-Hospital Cardiac Arrest at Home and in Public Locations.

Importance: Little is known about the influence of comprehensive public health initiatives according to out-of-hospital cardiac arrest (OHCA) location, particularly at home, where resuscitation efforts and outcomes have historically been poor.

Objective: To describe temporal trends in bystander cardiopulmonary resuscitation (CPR) and first-responder defibrillation for OHCAs stratified by home vs public location and their association with survival and neurological outcomes.

Design, Setting, And Participants: This observational study reviewed 8269 patients with OHCAs (5602 [67.

Parkinson's disease associated with pure repeat expansion.

Large, non-coding pentanucleotide repeat expansions of ATTCT in intron 9 of the gene typically cause progressive spinocerebellar ataxia with or without seizures and present neuropathologically with Purkinje cell loss resulting in symmetrical cerebellar atrophy. These repeat expansions can be interrupted by sequence motifs which have been attributed to seizures and are likely to act as genetic modifiers. We identified a Mexican kindred with multiple affected family members with expansions.

Direct Transport to a Percutaneous Cardiac Intervention Center and Outcomes in Patients With Out-of-Hospital Cardiac Arrest.

Background: Practice guidelines recommend regional systems of care for out-of-hospital cardiac arrest. However, whether emergency medical services should bypass nonpercutaneous cardiac intervention (non-PCI) facilities and transport out-of-hospital cardiac arrest patients directly to PCI centers despite longer transport time remains unknown.

Methods And Results: Using the Cardiac Arrest Registry to Enhance Survival with geocoding of arrest location, we identified out-of-hospital cardiac arrest patients with prehospital return of spontaneous circulation and evaluated the association between direct transport to a PCI center and outcomes in North Carolina during 2012 to 2014.

Complete Genome Sequence of Strain CCRI-195ME, Isolated from the Middle Ear.

is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we report the complete genome sequence of strain CCRI-195ME, which contains the phase-variable epigenetic regulator ModM3.

Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies.

Impact of Early Vasopressor Administration on Neurological Outcomes after Prolonged Out-of-Hospital Cardiac Arrest.

Unlabelled: Introduction Vasopressors are associated with return of spontaneous circulation (ROSC), but no long-term benefit has been demonstrated in randomized trials. However, these trials did not control for the timing of vasopressor administration which may influence outcomes. Consequently, the objective of this study was to develop a model describing the likelihood of favorable neurological outcome (cerebral performance category [CPC] 1 or 2) as a function of the public safety answering point call receipt (PSAP)-to-pressor-interval (PPI) in prolonged out-of-hospital cardiac arrest.

Methods for Genome-Wide Methylome Profiling of Campylobacter jejuni.

Methylation has a profound role in the regulation of numerous biological processes in bacteria including virulence. The study of methylation in bacteria has greatly advanced thanks to next-generation sequencing technologies. These technologies have expedited the process of uncovering unique features of many bacterial methylomes such as characterizing previously uncharacterized methyltransferases, cataloging genome-wide DNA methylations in bacteria, identifying the frequency of methylation at particular genomic loci, and revealing regulatory roles of methylation in the biology of various bacterial species.