Faculty Bibliography

INTRODUCTION:As the utility of genomic sequencing increases, its use in healthcare will continue to expand beyond expert clinics toward nonspecialist practices such as primary care. At the same time, discordance in genetic variant identification and classification between laboratories remains a concern for the field. This research assesses how clinicians with and without genetics expertise understand and trust genetic test results, underscoring how variation in the handling of genetic test results can have real impact on patient care. METHODS:We conducted 40 interviews with genetics experts, including clinical geneticists and genetic counselors, and nonexpert clinicians including primary care providers and cardiologists. RESULTS:Clinical geneticists and genetic counselors reported spending significant time assessing the validity of results from genetic testing laboratories, conversing with laboratories about those results, and potentially reinterpreting results. Conversely, primary care providers and cardiologists without specific genetics expertise reported high levels of trust in laboratory accuracy and variant interpretation, and did not reassess results. CONCLUSION:We find significant variation in how genetics experts and nonexperts understand the trustworthiness of genetic laboratory reports. This variation could lead to differences in patient care between clinical settings and requires additional guidance for clinicians regarding the handling of genetic test results.

State and local health departments were responsible for ensuring equitable distribution of the COVID-19 vaccine. This qualitative study aimed to identify the challenges, strategies, disappointments, and successes in achieving equity for hard-to-reach and at-risk populations. Using a purposive sampling strategy, 16 individuals affiliated with health departments across nine states, each holding leadership roles in vaccine distribution, were interviewed between late 2021 and mid-2022. The key factors promoting vaccine equity included (1) inviting community members to serve on vaccine advisory groups to participate in decision-making; (2) utilizing pre-existing community relationships and spaces to facilitate the planning and distribution of the vaccine; and (3) establishing and building upon community outreach to support accessibility and uptake of the vaccine. The barriers included (1) a lack of clarity on vaccine prioritization criteria; (2) language/communication access; and (3) the initial focus on mass vaccination sites for vaccine delivery. The stakeholders also highlighted potential facilitators for increasing equity in future vaccine rollouts. Overall, community engagement emerged as a critical factor in ensuring equity during disaster response efforts.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a major driver of cirrhosis and liver-related mortality. However, therapeutic options for MASLD, including prevention of liver steatosis, are limited. We previously described that vasoactive intestinal peptide-producing neurons (VIP-neurons) regulate the efficiency of intestinal dietary fat absorption and IL-22 production by type 3 innate lymphoid cells (ILC3) in the intestine. Given the described hepatoprotective role of IL-22, we hypothesize that modulation of this neuroimmune circuit could potentially be an innovative approach for the control of liver steatosis. METHODS:We used a model of diet-induced MASLD by exposing mice to a high-fat diet (HFD) for 16 weeks, when the development of liver steatosis was first observed in our animals. We characterized IL-22 production by intestinal ILC3 at this dietary endpoint. We then evaluated whether communication between VIP-neurons and ILC3 affected IL-22 production and MASLD development by exposing mice with a conditional genetic deletion of Vipr2 in ILC3 (Rorc(t)CreVipr2fl/fl) to the HFD. We also performed intermittent global inhibition of VIP-neurons using a chemogenetic inhibitory approach (VipIres-CrehM4DiLSL) in HFD-fed mice. RESULTS:Production of IL-22 by intestinal ILC3 is reduced in steatotic mice that were exposed to an HFD for 16 weeks. Targeted deletion of VIP receptor 2 in ILC3 resulted in higher production of IL-22 in ILC3 and was associated with a significant reduction in liver steatosis in mice under HFD. Global inhibition of VIP-producing neurons also resulted in a significant reduction in liver steatosis. CONCLUSIONS:Modulating VIPergic neuroimmune signaling can ameliorate the development of hepatic steatosis induced by a surplus of fat ingestion in the diet. This neuroimmune pathway should be further investigated as a potential therapeutic avenue in MASLD.

This study evaluated the survival probabilities of two lithia-based glass-ceramics after final crystallization in a microwave furnace using conventional crystallization as a reference. Disc-shaped samples of a lithium silicate (LS, Celtra Duo) and a lithium disilicate (LD, e.max CAD) were prepared and divided into two groups according to the crystallization method (n = 30): microwave (M) or conventional furnaces (C). The biaxial flexural strength test was used to determine the fatigue test profile and its parameters. Then, specimens were submitted to an accelerated life test (step stress) using three profile levels - mild, moderate, and aggressive - varying the load increments and the number of cycles until fracture (4 Hz). Survival data were used to calculate Weibull's beta (β) value and reliability of the assigned missions. Scanning electron microscopy was employed to analyze surface morphology, fracture characteristics, and failure patterns. Beta (β) values for the LS-C, LS-M, LD-C, and LD-M groups were 2.65, 0.25, 0.62, and 0.3, respectively. Similar reliability was observed in all groups after 50,000 cycles at 100 and 150 Mpa. At 200 Mpa, the crystallization method did not affect the reliability within LS or LD. However, LD showed greater reliability than LS when crystallized by microwave energy. Thus, microwave energy can be suggested as an alternative to the process of conventional lithia-based glass-ceramics crystallization without damaging their survival probabilities.

Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35-75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Operating rooms (ORs) are critical for hospital revenue and cost management, with utilization efficiency directly affecting financial outcomes. Traditional surgical scheduling often results in suboptimal OR use. We aim to build a machine learning (ML) model to predict incision times for robotic-assisted hysterectomies, enhancing scheduling accuracy and hospital finances. METHODS/UNASSIGNED:A retrospective study was conducted using data from robotic-assisted hysterectomy cases performed between January 2017 and April 2021 across 3 hospitals within a large academic health system. Cases were filtered for surgeries performed by high-volume surgeons and those with an incision time of under 3 hours (n = 2,702). Features influencing incision time were extracted from electronic medical records and used to train 5 ML models (linear ridge regression, random forest, XGBoost, CatBoost, and explainable boosting machine [EBM]). Model performance was evaluated using a dynamic monthly update process and novel metrics such as wait-time blocks and excess-time blocks. RESULTS/UNASSIGNED: < .001, 95% CI [-329 to -89]), translating to approximately 52-hours over the 51-month study period. The model predicted more surgeries within a 15% range of the true incision time compared to traditional methods. Influential features included surgeon experience, number of additional procedures, body mass index (BMI), and uterine size. CONCLUSION/UNASSIGNED:The ML model enhanced the prediction of incision times for robotic-assisted hysterectomies, providing a potential solution to reduce OR underutilization and increase surgical throughput and hospital revenue.

Image-guided biopsy is an integral step in the diagnosis and management of suspicious image-detected breast or axillary lesions, allowing for accurate diagnosis and, if indicated, treatment planning. Tissue sampling can be performed under guidance of a full spectrum of breast imaging modalities, including stereotactic, tomosynthesis, sonographic, and MRI, each with its own set of advantages and limitations. Procedural planning, which includes consideration of technical, patient, and lesion factors, is vital for diagnostic accuracy and limitation of complications. The purpose of this paper is to review and provide guidance for breast imaging radiologists in selecting the best procedural approach for the individual patient to ensure accurate diagnosis and optimal patient outcomes. Common patient and lesion factors that may affect successful sampling and contribute to postbiopsy complications are reviewed and include obesity, limited patient mobility, patient motion, patients prone to vasovagal reactions, history of anticoagulation, and lesion location, such as proximity to vital structures or breast implant.

"See Your Dentist Twice a Year" is the standard of care today honored by dentists, requested by patients, and covered by insurance. Where is the scientific evidence to support this dictate? Several systematic reviews could find no support for or against it. When did it start? This paper traces the timeline of the statement and its appearance in toothpaste advertisements. It was first spotted in 1890 as part of a household guide for beauty preservation. Subsequently, the idea became a tagline in dental advertisements for Colgate Ribbon Toothpaste, Dr. Lyon's Dentifrice from 1913, and Pepsodent toothpaste starting in 1926.

Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratified, identity-by-descent sharing between siblings to unbiasedly estimate heritability of height (0.76 ± 0.05) and BMI (0.55 ± 0.07). Our results imply that substantial heritability remains unaccounted for by GWAS-identified loci and this residual genetic variation is polygenic and enriched near these loci.