The Impact of Health Insurer Acquisitions of Physician Practices on Prices and Patient Visits.

Objective: To investigate whether the acquisition of physician practices by Optum, a subsidiary of United Health Group (UHG), influences patient volume and service prices, particularly, for patients enrolled in health insurance plans competing with UHG.

Study Setting And Design: We employed a novel database cataloging health insurer acquisitions of physician practices to identify those acquired by Optum-the nation's largest payvider (vertically integrated payer-provider)-from 2007 to 2023. These data were integrated with non-UHG commercial health insurance claims for practices acquired between 2015 and 2019.

Atlas-scale single-cell DNA methylation profiling with sciMETv3.

Single-cell methods to assess DNA methylation have not achieved the same level of cell throughput per experiment compared to other modalities, with large-scale datasets requiring extensive automation, time, and other resources. Here, we describe sciMETv3, a combinatorial indexing-based technique that enables atlas-scale libraries to be produced in a single experiment. To reduce the sequencing burden, we demonstrate the compatibility of sciMETv3 with capture techniques to enrich regulatory regions, as well as the ability to leverage enzymatic conversion, which can yield higher library diversity.

Single-cell DNA methylation analysis tool Amethyst reveals distinct noncanonical methylation patterns in human glial cells.

Single-cell sequencing technologies have revolutionized biomedical research by enabling deconvolution of cell type-specific properties in highly heterogeneous tissue. While robust tools have been developed to handle bioinformatic challenges posed by single-cell RNA and ATAC data, options for emergent modalities such as methylation are much more limited, impeding the utility of results. Here we present Amethyst, a comprehensive R package for atlas-scale single-cell methylation sequencing data analysis.

Increased intake of tree forage by moose is associated with intake of crops rich in nonstructural carbohydrates.

Animals representing a wide range of taxonomic groups are known to select specific food combinations to achieve a nutritionally balanced diet. The nutrient balancing hypothesis suggests that, when given the opportunity, animals select foods to achieve a particular target nutrient balance, and that balancing occurs between meals and between days. For wild ruminants who inhabit landscapes dominated by human land use, nutritionally imbalanced diets can result from ingesting agricultural crops rich in starch and sugar (nonstructural carbohydrates [NCs]), which can be provided to them by people as supplementary feeds.

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds.

sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden.

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap).

Factors that influence performance in pediatric cochlear implant recipients with cochlear nerve deficiency.

Objectives: Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance.

Methods: The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital.

Accessible high-throughput single-cell whole-genome sequencing with paired chromatin accessibility.

Single-cell whole-genome sequencing (scWGS) enables the assessment of genome-level molecular differences between individual cells with particular relevance to genetically diverse systems like solid tumors. The application of scWGS was limited due to a dearth of accessible platforms capable of producing high-throughput profiles. We present a technique that leverages nucleosome disruption methodologies with the widely adopted 10× Genomics ATAC-seq workflow to produce scWGS profiles for high-throughput copy-number analysis without new equipment or custom reagents.

sciMET-cap: High-throughput single-cell methylation analysis with a reduced sequencing burden.

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap).

Comparison of Two Place-Based Mapping Procedures on Masked Sentence Recognition as a Function of Electrode Array Angular Insertion Depth and Presence of Acoustic Low-Frequency Information: A Simulation Study.

Introduction: Cochlear implant (CI) and electric-acoustic stimulation (EAS) users may experience better performance with maps that align the electric filter frequencies to the cochlear place frequencies, known as place-based maps, than with maps that present spectrally shifted information. Individual place-based mapping procedures differ in the frequency content that is aligned to cochlear tonotopicity versus discarded or spectrally shifted. The performance benefit with different place-based maps may vary due to individual differences in angular insertion depth (AID) of the electrode array and whether functional acoustic low-frequency information is available in the implanted ear.

Atlas-scale single-cell chromatin accessibility using nanowell-based combinatorial indexing.

Here we present advancements in single-cell combinatorial indexed Assay for Transposase Accessible Chromatin (sciATAC) to measure chromatin accessibility that leverage nanowell chips to achieve atlas-scale cell throughput (>10 cells) at low cost. The platform leverages the core of the sciATAC workflow where multiple indexed tagmentation reactions are performed, followed by pooling and distribution to a second set of reaction wells for polymerase chain reaction (PCR)-based indexing. In this work, we instead leverage a chip containing 5184 nanowells at the PCR stage of indexing, enabling a 52-fold improvement in scale and reduction in per-cell preparation costs.

Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation.

High-throughput robust single-cell DNA methylation profiling with sciMETv2.

DNA methylation is a key epigenetic property that drives gene regulatory programs in development and disease. Current single-cell methods that produce high quality methylomes are expensive and low throughput without the aid of extensive automation. We previously described a proof-of-principle technique that enabled high cell throughput; however, it produced only low-coverage profiles and was a difficult protocol that required custom sequencing primers and recipes and frequently produced libraries with excessive adapter contamination.

Cas12a-Capture: A Novel, Low-Cost, and Scalable Method for Targeted Sequencing.

Targeted sequencing remains a valuable technique for clinical and research applications. However, many existing technologies suffer from pervasive guanine-cytosine (GC) sequence content bias, high input DNA requirements, and high cost for custom panels. We have developed Cas12a-Capture, a low-cost and highly scalable method for targeted sequencing.

Effect of Place-Based Versus Default Mapping Procedures on Masked Speech Recognition: Simulations of Cochlear Implant Alone and Electric-Acoustic Stimulation.

Purpose: Cochlear implant (CI) recipients demonstrate variable speech recognition when listening with a CI-alone or electric-acoustic stimulation (EAS) device, which may be due in part to electric frequency-to-place mismatches created by the default mapping procedures. Performance may be improved if the filter frequencies are aligned with the cochlear place frequencies, known as place-based mapping. Performance with default maps versus an experimental place-based map was compared for participants with normal hearing when listening to CI-alone or EAS simulations to observe potential outcomes prior to initiating an investigation with CI recipients.

Deeply conserved synteny and the evolution of metazoan chromosomes.

Animal genomes show networks of deeply conserved gene linkages whose phylogenetic scope and chromosomal context remain unclear. Here, we report chromosome-scale conservation of synteny among bilaterians, cnidarians, and sponges and use comparative analysis to reconstruct ancestral chromosomes across major animal groups. Comparisons among diverse metazoans reveal the processes of chromosome evolution that produced contemporary karyotypes from their Precambrian progenitors.

Insertion Depth and Cochlear Implant Speech Recognition Outcomes: A Comparative Study of 28- and 31.5-mm Lateral Wall Arrays.

Objectives: 1) To compare speech recognition outcomes between cochlear implant (CI) recipients of 28- and 31.5-mm lateral wall electrode arrays, and 2) to characterize the relationship between angular insertion depth (AID) and speech recognition.

Study Design: Retrospective review.

Relationship Between Intraoperative Electrocochleography and Hearing Preservation.

Objectives: To compare intraoperative intracochlear electrocochleography (ECochG) with hearing preservation outcomes in cochlear implant (CI) subjects.

Design: Intraoperative electrocochleography was performed in adult CI subjects who were recipients of Advanced Bionics' Bionics LLC precurved HiFocus MidScala or straight HiFocus SlimJ electrode arrays. ECochG responses were recorded from the most apical electrode contact during insertion.

High-content single-cell combinatorial indexing.

Single-cell combinatorial indexing (sci) with transposase-based library construction increases the throughput of single-cell genomics assays but produces sparse coverage in terms of usable reads per cell. We develop symmetrical strand sci ('s3'), a uracil-based adapter switching approach that improves the rate of conversion of source DNA into viable sequencing library fragments following tagmentation. We apply this chemistry to assay chromatin accessibility (s3-assay for transposase-accessible chromatin, s3-ATAC) in human cortical and mouse whole-brain tissues, with mouse datasets demonstrating a six- to 13-fold improvement in usable reads per cell compared with other available methods.

Influence of Cochlear Implant Use on Perceived Listening Effort in Adult and Pediatric Cases of Unilateral and Asymmetric Hearing Loss.

Objective: Assess the influence of cochlear implant (CI) use on the perceived listening effort of adult and pediatric subjects with unilateral hearing loss (UHL) or asymmetric hearing loss (AHL).

Study Design: Prospective cohort.

Setting: Tertiary referral center.