Medicine and Health Sciences Commons^™

Prdm16 Enhances Osteoblastogenic Runx2 Via Canonical Wnt10b/Β-Catenin Pathway In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Mia Prado, Virginia Fuenmayor Lopez, Georgia Colleluori, Lina Aguirre, Rui Chen, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

We previously reported that PRDM16 mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that Prdm16 regulates Runx2, an important osteoblastic transcription factor, expression and activity. However, the changes in PRDM16, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling …

Small Variant Benchmark From A Complete Assembly Of X And Y Chromosomes, Justin Wagner, Nathan D Olson, Jennifer Mcdaniel, Lindsay Harris, Brendan J Pinto, David Jáspez, Adrián Muñoz-Barrera, Luis A Rubio-Rodríguez, José M Lorenzo-Salazar, Carlos Flores, Sayed Mohammad Ebrahim Sahraeian, Giuseppe Narzisi, Marta Byrska-Bishop, Uday S Evani, Chunlin Xiao, Juniper A Lake, Peter Fontana, Craig Greenberg, Donald Freed, Mohammed Faizal Eeman Mootor, Paul C Boutros, Lisa Murray, Kishwar Shafin, Andrew Carroll, Fritz J Sedlazeck, Melissa Wilson, Justin M Zook

Faculty, Staff and Students Publications

The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets. We show how complete assemblies can expand benchmarks to difficult regions, but highlight …

Mergers And Acquisitions (M&As) In Pharmaceutical Markets: Associations With Market Concentration, Prices, Drug Quantity Sold, And Shortages, J. Daniel Mcgeeney M.S., Aylin Sertkaya Ph.D., Leah Ross M.A., Fred Ledley M.D., Cody Hyman Ph.D.

CISI Publication

In recent decades, the pharmaceutical industry has become increasingly concentrated in the United States, in part due to mergers and acquisitions (M&As) between drug manufacturers. This consolidation from M&As has been cited as a key factor affecting drug prices and drug shortages (U.S. Federal Trade Commission, 2022). In this study, we assessed trends in pharmaceutical M&As during 2010–2023 and evaluated the characteristics of drugs and companies involved in those M&As. We considered the effects of M&As on market concentration, drug prices, drug quantity sold, and drug shortages. We also considered how these associations vary by drug characteristics, including brand drugs …

Application Of Core Functions And Forms In Complex Health Intervention Research: A Scoping Review Protocol, Katelyn Fox, Debbie Passey, Eunyoung Kang, Laura Zeigen, Erin Kenzie, Jessica D Austin, Rachel J Meadows, Maria E Fernandez, Monica Perez Jolles

Faculty, Staff and Student Publications

Introduction: The ability of healthcare, community and public health systems to effectively implement and disseminate research innovations depends on contextual factors at multiple interconnected levels of influence (eg, the innovation, individual, provider/implementor, organisation and health system). Recently, there has been an increase in the development of complex interventions designed to target multiple levels, designed for or adapted to the context in which they are delivered. Two concepts from complex systems thinking have been increasingly used to operationalise such interventions-core functions (theory and evidence-driven purposes of interventions) and forms (adaptable activities that perform each core function). However, there is a gap …

Treatment Of E-Cigarette Use Among Hospitalised Adolescents And Young Adults: A Protocol For Intervention Development And Evaluation Of Preliminary Efficacy And Implementation Outcomes In A Randomised Controlled Trial., Shelbie Wooten, Delwyn Catley, Melissa K. Miller, Karen Wilson, Kimber P. Richter, Abbey Masonbrink

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Hospitalisation represents an opportunity to identify and treat e-cigarette use among adolescents and young adults (AYAs). Knowledge on how to provide this care is lacking. We aim to fill this gap by developing an e-cigarette use intervention and evaluating preliminary efficacy and implementation outcomes among hospitalised AYAs.

METHODS AND ANALYSIS: We will enrol 144 hospitalised AYAs (14-21 years) who report past 30-day e-cigarette use and randomise 2:1 to intervention or control arms. We will develop an evidence-based intervention that includes education, motivational interviewing, quit planning and nicotine replacement therapy prescription offered confidentially in person during the hospital stay and …

Clinical And Imaging Features Of Head And Neck Metastasis Of High-Grade Glioma: A Single-Center Case Series, Rami W Eldaya, Diana Kaya, Michelle Williams, Susana Calle, Dawid Schellingerhout

Faculty, Staff and Student Publications

High-grade gliomas are the most frequent primary brain tumors, yet extraneural metastasis is exceedingly rare. This is in part secondary to the relatively poor survival of these patients and likely the shielding effect of the blood-brain barrier. Given the rarity of extraneural metastasis, the pathophysiology and imaging appearance of extraneural metastasis is under-reported and poorly understood. In this case series we present 6 patients with pathology-confirmed high-grade glioma and extraneural head and neck metastasis. We highlight imaging features of metastasis on CT, MRI, and PET/CT. We also explore potential correlations and pathophysiology of high-grade glioma metastasis to the head and …

Genetic Variations In Mdm2 Gene Contribute To Renal Cell Carcinoma Susceptibility: A Genotype–Phenotype Correlation Study, Shu-Yu Chang, Wen-Shin Chang, Hou-Yu Shih, Chao-Hsiang Chang, Hsi-Chin Wu, Chia-Wen Tsai, Yun-Chi Wang, Jian Gu, Da-Tian Bau

Faculty, Staff and Student Publications

Background: This study aimed to investigate the polymorphic genotypes of MDM2 rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of MDM2 genotypes and environmental factors on RCC susceptibility.

Methods: A total of 135 RCC patients and 590 controls were recruited for MDM2 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients.

Results: MDM2 rs2279744, but not other polymorphisms, was significantly associated with an increased RCC risk (p = 0.0133). The MDM2 rs2279744 G allele was identified as …

Gene Signatures Derived From Transcriptomic-Causal Networks Stratify Colorectal Cancer Patients For Effective Targeted Therapy, Akram Yazdani, Heinz-Josef Lenz, Gianluigi Pillonetto, Raul Mendez-Giraldez, Azam Yazdani, Hanna Sanoff, Reza Hadi, Esmat Samiei, Alan P Venook, Mark J Ratain, Naim Rashid, Benjamin G Vincent, Xueping Qu, Yujia Wen, Michael Kosorok, William F Symmans, John Paul Y C Shen, Michael S Lee, Scott Kopetz, Andrew B Nixon, Monica M Bertagnolli, Charles M Perou, Federico Innocenti

Faculty, Staff and Student Publications

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes. This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. The patients were enrolled in a randomized clinical trial receiving either cetuximab or bevacizumab in combination with chemotherapy. An external cohort of paired CRC normal and tumor …

Venetoclax-Based Combination Regimens In Acute Myeloid Leukemia, Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D Dinardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.

Society For Immunotherapy Of Cancer: Updates And Best Practices For Multiplex Immunohistochemistry (Ihc) And Immunofluorescence (If) Image Analysis And Data Sharing, Janis M Taube, Joel C Sunshine, Michael Angelo, Guray Akturk, Margaret Eminizer, Logan L Engle, Cláudia S Ferreira, Sacha Gnjatic, Benjamin Green, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Daniel Jiménez-Sánchez, Konstanty Korski, Ana Lako, Edwin R Parra, Marlon C Rebelatto, David L Rimm, Scott J Rodig, Jamie Rodriguez-Canales, Jeffrey S Roskes, Kurt A Schalper, Emanuel Schenck, Keith E Steele, Michael J Surace, Alexander S Szalay, Michael T Tetzlaff, Ignacio I Wistuba, Jennifer H Yearley, Carlo B Bifulco

Faculty, Staff and Student Publications

Objectives: Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force. The current effort represents a complementary manuscript for mIHC/IF analysis focused on the associated image analysis and data management.

Methods: The Society for Immunotherapy of Cancer convened a task …

Leveraging A New Data Resource To Define The Response Of Cryptococcus Neoformans To Environmental Signals, Yu Sung Kang, Jeffery Jung, Holly L Brown, Chase Mateusiak, Tamara L Doering, Michael R Brent

2020-Current year OA Pubs

Cryptococcus neoformans is an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of 5 signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-seq in quadruplicate, yielding 881 RNA-seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either …

A Sequencing Overview Of Malignant Peripheral Nerve Sheath Tumors: Findings And Implications For Treatment, Kangwen Xiao, Kuangying Yang, Angela C Hirbe

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies with a low 5-year survival rate despite current treatments. MPNSTs frequently harbor mutations in key genes such as

Waste Clearance Shapes Aging Brain Health, Li-Feng Jiang-Xie, Antoine Drieu, Jonathan Kipnis

2020-Current year OA Pubs

Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer's and Parkinson's diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.

Commensal-Pathogen Dynamics Structure Disease Outcomes During Clostridioides Difficile Colonization, Skye R S Fishbein, Anna L Deveaux, Sakshi Khanna, Aura L Ferreiro, James Liao, Wesley Agee, Jie Ning, Bejan Mahmud, Miranda J Wallace, Tiffany Hink, Kimberly A Reske, Candice Cass, Janaki Guruge, Sidh Leekha, Sunaina Rengarajan, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical outcomes. Microbiota humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clinically prevalent clade 1 lineages and identified candidate taxa, including Blautia, as markers of stable colonization. Using gnotobiotic mice engrafted with defined human microbiota, we validated strain-specific CDI severity across clade 1 strains isolated from patients. Mice engrafted …

Development Of A Metabolome-Based Respiratory Infection Prognostic During Covid-19 Arrival, John I Robinson, Laura R Marks, Andrew L Hinton, Jane A O'Halloran, Charles W Goss, Peter J Mucha, Jeffrey P Henderson

2020-Current year OA Pubs

In a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology. We obtained urine specimens from 163 patients presenting for evaluation. We obtained LC-MS profiles in the initial cohort and used machine learning methods …

Homecoming Mom Returns To Wise After Three Years Absence, Madelyn Lawrence

Virginia Dental Journal

Madelyn Lawrence, a VCU School of Dentistry student and UVA-Wise alum, shares her transformative experience with the Mission of Mercy (MOM) project in Wise, Virginia. Initially volunteering in 2019, she witnessed the profound impact of providing free dental care to underserved rural communities. Returning as a dental student, she felt a deep connection to the patients and recognized the critical need for accessible dental care in such areas. Lawrence urges dental professionals to volunteer for projects like MOM, emphasizing the life-changing benefits for both providers and recipients.

How Can Financial Planning Software Help You Plan For Retirement?, Jeremy Pickett

Virginia Dental Journal

Financial planning software helps retirees navigate the complexities of retirement by considering various factors like assets, liabilities, income sources, and expenses. Unlike the simplistic four percent rule, modern software uses Monte Carlo Simulation to account for uncertainties such as sequence of return risk. This allows retirees to model different scenarios, make informed decisions, and adjust their plans over time to ensure financial stability throughout retirement.

Do You Know How To Prevent Financial Fraud In Your Dental Practice?, Phil Nieto

Virginia Dental Journal

Financial fraud is a significant concern for dental practices, with an estimated 20%-60% of dentists affected over their careers. To prevent embezzlement, dentists should utilize the security functions of their practice management software, including setting high-level user permissions and audit logs. Daily checks on patient returns and weekly audits of financial consistency are crucial. Monitoring these areas can help detect and deter fraudulent activities, ensuring the financial health of the practice.

Reduce Costs And Boost Profits, Robert Mcdermott

Virginia Dental Journal

Dental practices face significant challenges with time-consuming tasks like insurance verification, which can be streamlined through automation. Automated dental insurance verification can save nearly 30 hours a week, effectively adding a full-time employee without the overhead. This not only reduces costs but also improves patient care by identifying revenue and treatment opportunities. Additionally, revenue analytics tools help practices stay on top of patient eligibility and uncollected accounts, boosting overall profits. Solutions like iCoreConnect's cloud-based products offer comprehensive tools to enhance productivity and financial growth for both solo practices and DSOs.

Vda Member Perks Announces Expanded Endorsement With Icoreconnect, Elise Rupinski

Virginia Dental Journal

The VDA Member Perks Program has expanded its endorsement of iCoreConnect, adding five new services to its portfolio. Building on previous endorsements of HIPAA-compliant email, ePrescription software, and automated insurance verification, the new services include iCoreCloud for data backup, iCoreCodeGenius for medical coding, iCoreHuddle for analytics, iCoreHuddle+ for detailed practice metrics, and iCoreIT for managed IT services. These tools aim to enhance productivity and profitability for VDA members, who also receive exclusive savings on these services.

Social Media Trends And Tips For 2023, Michaela Mishoe

Virginia Dental Journal

In 2023, social media trends emphasize the importance of short-form videos, such as TikTok and Instagram Reels, to engage audiences. Educational content that adds value and is easy to understand can help break through the clutter. Collaborating with micro-influencers and other healthcare providers can expand reach and credibility. Regularly analyzing social media performance can guide content strategy adjustments. Lastly, maintaining authenticity in content is crucial for building trust and effectively communicating your practice's values.

Virginia Board Of Dentistry Notes December 2, 2022, Ursula Klostermyer Dds, Phd

Virginia Dental Journal

The Virginia Board of Dentistry meeting on December 2, 2022, addressed several key issues. New Director of the Department of Health Professions, Mr. Arne W. Owens, acknowledged workforce shortages and proposed new ideas to tackle them. The Board discussed regulatory updates, including simplifying language and reducing reactivation costs for inactive licenses. They clarified procedures for taking vital signs during sedation and increased continuing education hours for dentists and dental hygienists providing free services to low-income individuals. The disciplinary report revealed that most closed cases were patient care-related, with some resulting in license suspensions.

Update: Smiles For Children Program (Medicaid), Roger Palmer

Virginia Dental Journal

The Smiles for Children program, part of Virginia's Medicaid, has expanded to provide comprehensive dental care to adults as of July 2021. This includes treatments like endodontics, crowns, and dentures. Despite a 30% fee increase in 2022, there is a shortage of participating dentists to meet the high demand. Dr. Roger Palmer encourages more dentists to join the program to help underserved populations, highlighting the satisfaction of restoring dental health and the streamlined payment process. For more information, dentists can contact Dr. Palmer directly.

Our Success Is Your Success, Laura Givens

Virginia Dental Journal

The Virginia Dental Association (VDA) successfully advocated for a 30% increase in dental Medicaid reimbursement rates, securing $116 million in new funding. The VDA is actively seeking contributions to its Political Action Committee (PAC) and encouraging participation in advocacy events like Dental Days at the Capitol. The 2022 contributions report shows varying levels of success across different regions, with a total of $298,492 raised, falling short of the $375,000 goal.

Reflections On Dentistry In The Year 2022, Gary Oyster Dds

Virginia Dental Journal

In 2022, the dental profession faced ongoing challenges from COVID-19, including workforce shortages. The ADA is working to address staffing issues and improve member engagement through initiatives like the SmileCon meeting and a new mobile app. Efforts are also underway to introduce legislation for a Medical Loss Ratio in dental plans across multiple states. Membership remains a priority, with a focus on engaging young dentists and those working for Dental Service Organizations (DSOs). The ADA aims to make all dentists feel welcome and involved.

School Days, Richard F. Roadcap Dds

Virginia Dental Journal

In the 1980s, Garrison Keillor's radio show humorously suggested that all children are above average, reflecting a modern culture where failure is often avoided. The document discusses the challenges faced by students in Organic Chemistry, particularly at New York University (NYU), where students petitioned for the dismissal of Dr. Maitland Jones Jr. due to his strict grading. This incident raises questions about whether academic standards should be relaxed for aspiring healthcare professionals and the implications of such actions on the quality of future providers. The author reflects on personal academic struggles and emphasizes the importance of overcoming failures to achieve …

Let’S Start The Year Off Right, Cynthia Southern Dds

Virginia Dental Journal

Dr. Cynthia Southern, in her New Year message, highlights a significant victory in Massachusetts where voters approved a dental loss ratio of 83% for insurance companies, similar to medical insurance under the Affordable Care Act. She urges other states, including Virginia, to adopt similar legislation to improve dental care coverage and reimbursement rates. Dr. Southern also addresses the 30% increase in Medicaid reimbursement rates and the ongoing workforce shortage in dental offices. She encourages contributions to the VDA Tooth PAC, recruitment of new members, and participation in Dental Days at the Capitol to advocate for these changes.

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

Nutritional, Phytochemical, And Antimicrobial Properties Of Carica Papaya Leaves: Implications For Health Benefits And Food Applications, Rajni Choudhary, Ravinder Kaushik, Ansab Akhtar, Suvendu Manna, Jyoti Sharma, Aarti Bains

School of Medicine Faculty Publications

BACKGROUND: Papaya leaves (PLs) are known for their therapeutic benefits and traditional use in treating inflammation, infections, and various health conditions. Rich in bioactive compounds, PLs are studied for their potential applications in functional foods. This study analyzed their nutritional, phytochemical, structural, thermal, and antimicrobial properties to evaluate their role as a health-promoting ingredient. METHODS: Phytochemicals were quantified spectrophotometrically and identified via GC-MS. Antioxidant activity was assessed using DPPH and FRAP assays. Mineral content was determined using ICP-OES. Structural and thermal properties were evaluated using FTIR, XRD, and calorimetry, and antimicrobial activity was tested via the agar well diffusion method. …

Achilles Tendon Morphology Adaptations In Chronic Post-Stroke Hemiparesis: A Comparative Analysis With Neurologically Intact Controls, Jing Nong Liang, Greg Bashford, Kornelia Kulig, Kai-Yu Ho

Physical Therapy Faculty Research

Introduction: In individuals with chronic post-stroke hemiparesis, slow walking speed is a significant concern related to inadequate propulsion of the paretic limb. However, an overlooked factor is this population's altered morphology of the Achilles tendon, which may compromise the propulsive forces by the paretic limb. This study aimed to explore changes in Achilles tendon morphology, including gross thickness and intra-tendinous collagen fiber bundle organization, following stroke-induced brain lesions.

Methods: Fifteen individuals with chronic post-stroke hemiparesis (at least 6 months post-stroke) and 19 neurologically intact controls participated. Ultrasound imaging was used to evaluate Achilles tendon thickness and collagen organization in the …