Publications by authors named "David Cutler"

Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa.

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Importance: Low-value care is a persistent problem with direct and cascading harms. Telemedicine is now commonly used and may reduce low-value testing by introducing barriers to completing tests at a given visit or expand opportunities for low-value testing by contributing to higher visit volumes.

Objective: To quantify the association between telemedicine adoption and low-value testing among fee-for-service Medicare beneficiaries.

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Objective: To examine differences between patients treated in integrated systems of care and patients treated outside of such systems during the COVID pandemic in the use of primary and preventive care, emergency services, inpatient services, and mortality.

Data Sources And Study Setting: Data are used from all enrollees in traditional Medicare aged 66 and older.

Study Design: Difference-in-differences estimates are calculated from the pre-COVID time period (January 2019-February 2020) to the initial COVID time period (March-May 2020) and the ongoing COVID time period (June 2020-December 2021) for patients treated by primary care physicians working in a health system versus not, and by the type of health system.

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Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of approximately 1 in 35,000 live births, it is the most common form of syndromic clefting and may account for ~2% of all OFCs. The majority of VWS is attributed to genetic variants in (~70%) or (~5%), leaving up to 25% of individuals with VWS without a molecular diagnosis.

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Differential co-expression analysis (DCA) aims to identify genes in a pathway whose shared expression depends on a risk factor. While DCA provides insights into the biological activity of diseases, existing methods are limited to categorical risk factors and/or suffer from bias due to batch and variance-specific effects. We propose a new framework, Kernel-based Differential Co-expression Analysis (KDCA), that harnesses correlation patterns between genes in a pathway to detect differential co-expression arising from general (i.

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Rotating algae biofilm reactors (RABRs) can reduce energy requirements for wastewater reclamation but require further optimization for implementation at water resource recovery facilities (WRRF). Optimizing RABR operation is challenging because conditions at WRRF change frequently, and disregarding interaction terms related to these changes can produce incorrect conclusions about RABR behavior. This study evaluated the two-way interaction and main effects of four factors on the biomass productivity and phosphorus removal efficiency of a microalgae-bacteria biofilm grown in municipal anaerobic digester centrate, with factor levels and operating conditions selected to mimic a pilot RABR at a WRRF in Utah.

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Article Synopsis
  • Perianal fistulizing Crohn's disease is a severe condition with limited treatment options, especially affecting non-European populations, but the underlying genetic and cellular reasons are not well understood.
  • This study investigated rectal organoids from patients with and without Crohn's disease, analyzing gene expression at a single-cell level to identify specific pathways and cell types linked to the disease.
  • The findings revealed that organoids showed disease-related gene expression patterns and retained unique signatures related to gender and ancestry, indicating their potential for personalized research on Crohn's disease.
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Background: The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions.

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Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP.

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Objectives: This paper provides an examination of: (1) the frequency and net rates of change for general pediatric inpatient (GPI) unit closures and openings nationally and by state; (2) how often closures or openings are caused by GPI unit changes only or caused by hospital-level changes; and (3) the relationship between hospital financial status and system ownership and GPI unit closures or openings.

Methods: This study used the Health Systems and Providers Database (2011-2018) plus 3 data sources on hospital closures. We enumerated GPI unit closures and openings to calculate net rates of change.

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The prior authorization (PA) process consumes time and money on the part of patients, providers, and payers. While some research shows substantial possible savings in the PA process, identifying what different groups can do is not as well known. Thus, organizations have struggled to capture this opportunity.

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Family-based heritability estimates of complex traits are often considerably larger than their single-nucleotide polymorphism (SNP) heritability estimates. This discrepancy may be due to non-additive effects of genetic variation, including variation that interacts with other genes or environmental factors to influence the trait. Variance-based procedures provide a computationally efficient strategy to screen for SNPs with potential interaction effects without requiring the specification of the interacting variable.

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Article Synopsis
  • Congenital heart defects (CHDs) are prevalent in children with Down syndrome, affecting 40-50% of this population.
  • A study sequenced the genomes of a diverse group of children with Down syndrome, both with CHD and with normal hearts, to explore the genetic factors associated with these heart defects.
  • While no specific genetic variants reached significant levels, several loci were identified with suggestive links to risk factors for different types of CHD, providing insights into potential genetic contributors to these defects.
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Background: During the COVID-19 pandemic, patients with Alzheimer's disease and related dementias (ADRD) were especially vulnerable, and modes of medical care delivery shifted rapidly. This study assessed the impact of the pandemic on care for people with ADRD, examining the use of primary, emergency, and long-term care, as well as deaths due to COVID and to other causes.

Methods: Among 4.

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Article Synopsis
  • * It aims to fill gaps in existing research by focusing on clinicians' views about which care sites are suitable and by analyzing all possible locations for care shifts along with their potential savings.
  • * A large survey was conducted among various healthcare professionals, examining over 5000 care activities to determine how much care could be safely moved to different settings, with data analyzed between April 2022 and October 2023.
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Article Synopsis
  • US health care administrative spending hits around $1 trillion annually, with the financial transactions ecosystem accounting for about $200 billion of that.
  • Efficient systems in other industries show that immediate payment assurance and high automation can lead to cost savings.
  • By implementing interventions to streamline the financial processes, the health care system could potentially save $40 billion to $60 billion, with half of the savings coming from organizational improvements and the other half from broader industry-wide changes.
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Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP.

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The "missing" heritability of complex traits may be partly explained by genetic variants interacting with other genes or environments that are difficult to specify, observe, and detect. We propose a new kernel-based method called Latent Interaction Testing (LIT) to screen for genetic interactions that leverages pleiotropy from multiple related traits without requiring the interacting variable to be specified or observed. Using simulated data, we demonstrate that LIT increases power to detect latent genetic interactions compared to univariate methods.

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Telemedicine use remains substantially higher than it was before the COVID-19 pandemic, although it has fallen from pandemic highs. To inform the ongoing debate about whether to continue payment for telemedicine visits, we estimated the association of greater telemedicine use across health systems with utilization, spending, and quality. In 2020, Medicare patients receiving care at health systems in the highest quartile of telemedicine use had 2.

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Allele-specific methylation (ASM) is an epigenetic modification whereby one parental allele becomes methylated and the other unmethylated at a specific locus. ASM is most often driven by the presence of nearby heterozygous variants that influence methylation, but also occurs somatically in the context of genomic imprinting. In this study, we investigate ASM using publicly available single-cell reduced representation bisulfite sequencing (scRRBS) data on 608 B cells sampled from six healthy B cell samples and 1,230 cells from 11 chronic lymphocytic leukemia (CLL) samples.

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