Multi-omics analysis in primary T cells elucidates mechanisms behind disease-associated genetic loci.

Background: Genome-wide association studies (GWAS) have uncovered the genetic basis behind many diseases and conditions. However, most of these genetic loci affect regulatory regions, making the interpretation challenging. Chromatin conformation has a fundamental role in gene regulation and is frequently used to associate potential target genes to regulatory regions.

Assessing Baseline Knowledge and Usage Patterns of Sexual Orientation/Gender Identity Affirming Electronic Health Record Modules Within a Urology Division at a Single Tertiary Care Institution.

Objective: To evaluate how sexual orientation and gender identity (SOGI)-affirming electronic health record (EHR) modules (which enable seamless location and documentation of patient SOGI data) are being used by providers/staff within a urology practice.

Materials And Methods: All 120 patient-facing providers/staff at a tertiary urology program were offered a 39-question Qualtrics-based survey, which assessed respondents' cultural competency, baseline knowledge of SOGI EHR modules, and SOGI module usage patterns. Cultural competency was assessed using the LGBT-Development of Clinical Skills Scale (LGBT-DOCCS).

Prognostic significance of sarcomatoid features in metastatic renal cell carcinoma treated with cytoreductive nephrectomy and targeted therapy.

Introduction: The presence of sarcomatoid features in localized renal cell carcinoma (RCC) is associated with worse outcomes. We sought to use a national database to evaluate the outcomes and prognosis of metastatic RCC (mRCC) with sarcomatoid features treated with cytoreductive nephrectomy (CN) and targeted therapy (TT).

Methods: The National Cancer Database (2010-2013) was used to identify patients with mRCC at diagnosis.

Identification of Mechanisms by Which Genetic Susceptibility Loci Influence Systemic Sclerosis Risk Using Functional Genomics in Primary T Cells and Monocytes.

Objective: Systemic sclerosis (SSc) is a complex autoimmune disease with a strong genetic component. However, most of the genes associated with the disease are still unknown because associated variants affect mostly noncoding intergenic elements of the genome. We used functional genomics to translate the genetic findings into a better understanding of the disease.

Automated Machine Learning Segmentation and Measurement of Urinary Stones on CT Scan.

Objectives: To evaluate the performance of an engineered machine learning algorithm to identify kidney stones and measure stone characteristics without the need for human input.

Methods: We performed a cross-sectional study of 94 children and adults who had kidney stones identified on non-contrast CT. A previously developed deep learning algorithm was trained to segment renal anatomy and kidney stones and to measure stone features.

Association of Inherited Mutations in DNA Repair Genes with Localized Prostate Cancer.

Background: Identification of germline mutations in DNA repair genes has significant implications for the personalized treatment of individuals with prostate cancer (PrCa).

Objective: To determine DNA repair genes associated with localized PrCa in a diverse academic biobank and to determine genetic testing burden.

Design, Setting, And Participants: A cross-sectional study of 2391 localized PrCa patients was carried out.

Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays.

Genetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease.

Chromatin Looping Links Target Genes with Genetic Risk Loci for Dermatological Traits.

Chromatin looping between regulatory elements and gene promoters presents a potential mechanism whereby disease risk variants affect their target genes. In this study, we use H3K27ac HiChIP, a method for assaying the active chromatin interactome in two cell lines: keratinocytes and skin lymphoma-derived CD8+ T cells. We integrate public datasets for a lymphoblastoid cell line and primary CD4+ T cells and identify gene targets at risk loci for skin-related disorders.

Characterisation of CD4+ T-cell subtypes using single cell RNA sequencing and the impact of cell number and sequencing depth.

CD4+ T-cells represent a heterogeneous collection of specialised sub-types and are a key cell type in the pathogenesis of many diseases due to their role in the adaptive immune system. By investigating CD4+ T-cells at the single cell level, using RNA sequencing (scRNA-seq), there is the potential to identify specific cell states driving disease or treatment response. However, the impact of sequencing depth and cell numbers, two important factors in scRNA-seq, has not been determined for a complex cell population such as CD4+ T-cells.

Stakeholder Perspective on Opioid Stewardship After Prostatectomy: Evaluating Barriers and Facilitators From the Pennsylvania Urology Regional Collaborative.

Objective: To evaluate existing practice patterns and potential barriers to implementing opioid stewardship protocols after robot-assisted prostatectomies among providers in the Pennsylvania Urology Regional Collaborative.

Methods: The Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement initiative of 11 academic and community urology practices in Pennsylvania and New Jersey representing 97 urologists. PURC distributed a web-based survey of 24 questions, with 74 respondents, including 56 attendings, 11 residents, and 7 advanced practice providers.

Functional genomics in autoimmune diseases.

Associations between genetic loci and increased susceptibility to autoimmune disease have been well characterized, however, translating this knowledge into mechanistic insight and patient benefit remains a challenge. While improvements in the precision, completeness and accuracy of our genetic understanding of autoimmune diseases will undoubtedly be helpful, meeting this challenge will require two interlinked problems to be addressed: first which of the highly correlated variants at an individual locus is responsible for increased disease risk, and second what are the downstream effects of this variant. Given that the majority of loci are thought to affect non-coding regulatory elements, the second question is often reframed as what are the target gene(s) and pathways affected by causal variants.

Mapping DNA interaction landscapes in psoriasis susceptibility loci highlights KLF4 as a target gene in 9q31.

Background: Genome-wide association studies (GWAS) have uncovered many genetic risk loci for psoriasis, yet many remain uncharacterised in terms of the causal gene and their biological mechanism in disease. This is largely a result of the findings that over 90% of GWAS variants map outside of protein-coding DNA and instead are enriched in cell type- and stimulation-specific gene regulatory regions.

Results: Here, we use a disease-focused Capture Hi-C (CHi-C) experiment to link psoriasis-associated variants with their target genes in psoriasis-relevant cell lines (HaCaT keratinocytes and My-La CD8+ T cells).

A Model for Improving Health Care Quality for Transgender and Gender Nonconforming Patients.

Problem Definition: Transgender and gender nonconforming (TGNC) populations are disproportionately affected by limited health care access and poor health outcomes and commonly report discrimination and mistreatment in health care settings. Despite these disparities, comprehensive approaches to improve the quality of health care of TGNC patient populations are currently lacking.

Initial Approach: The Vanderbilt Program for LGBTQ Health has developed a multifaceted, community-engaged approach to improve the quality of health care of TGNC patients, which includes the creation of a transgender patient advocacy program, a community advisory board, and a transgender health clinic.

Preventing Excess Narcotic Prescriptions in New Robotic Surgery Discharges: The PENN Prospective Cohort Quality Improvement Initiative.

To reduce the amount of opioids prescribed at discharge after robotic surgery, we hypothesized that the majority patients do not require opioids for pain control after robotic urologic oncologic procedures. This prospective study aimed to reduce opioids prescribed at discharge after robot-assisted radical prostatectomy (RARP), robot-assisted radical nephrectomy (RARN), and robot-assisted partial nephrectomy (RAPN). Before 9/2018, 100% of patients were discharged on varying amounts of oxycodone (range: 75-337.

Chromatin interactions reveal novel gene targets for drug repositioning in rheumatic diseases.

Objectives: There is a need to identify effective treatments for rheumatic diseases, and while genetic studies have been successful it is unclear which genes contribute to the disease. Using our existing Capture Hi-C data on three rheumatic diseases, we can identify potential causal genes which are targets for existing drugs and could be repositioned for use in rheumatic diseases.

Methods: High confidence candidate causal genes were identified using Capture Hi-C data from B cells and T cells.

Improving Operating Room Efficiency.

Purpose Of Review: Operating rooms are critical financial centers for hospital systems, with surgical care representing about a third of all health care spending. However, not all of the costs are appropriate or necessary, as there are sometimes significant inefficiencies in how operating rooms are utilized.

Recent Findings: Recent innovations utilizing patient-centered data, systems principles from manufacturing industries, and enhanced communication processes have made significant improvements in improving operating room efficiency.

Identification of rheumatoid arthritis causal genes using functional genomics.

Over the past decade, genome-wide association studies have contributed a wealth of knowledge to our understanding of polygenic disorders such as rheumatoid arthritis. As the size of sample cohorts has improved so too have the computational and experimental methods used to robustly define variants associated with disease susceptibility. The challenge now remains to translate these findings into improved understanding of disease aetiology and patient care.

Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP.