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2025

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Full-Text Articles in Medicine and Health Sciences

Decreased Lipidated Apoe-Receptor Interactions Confer Protection Against Pathogenicity Of Apoe And Its Lipid Cargoes In Lysosomes, Jing L Guo, Alexandra Litvinchuk, David M Holtzman, Et Al. Jan 2025

Decreased Lipidated Apoe-Receptor Interactions Confer Protection Against Pathogenicity Of Apoe And Its Lipid Cargoes In Lysosomes, Jing L Guo, Alexandra Litvinchuk, David M Holtzman, Et Al.

2020-Current year OA Pubs

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation. Lipofuscin increased lysosomal accumulation of tau …


Tamm-Horsfall Protein Augments Neutrophil Netosis During Urinary Tract Infection, Vicki Mercado-Evans, Holly Branthoover, Claude Chew, Camille Serchejian, Alexander B Saltzman, Marlyd E Mejia, Jacob J Zulk, Ingrid Cornax, Victor Nizet, Kathryn A Patras Jan 2025

Tamm-Horsfall Protein Augments Neutrophil Netosis During Urinary Tract Infection, Vicki Mercado-Evans, Holly Branthoover, Claude Chew, Camille Serchejian, Alexander B Saltzman, Marlyd E Mejia, Jacob J Zulk, Ingrid Cornax, Victor Nizet, Kathryn A Patras

Faculty, Staff and Students Publications

Urinary neutrophils are a hallmark of urinary tract infection (UTI), yet the mechanisms governing their activation, function, and efficacy in controlling infection remain incompletely understood. Tamm-Horsfall glycoprotein (THP), the most abundant protein in urine, uses terminal sialic acids to bind an inhibitory receptor and dampen neutrophil inflammatory responses. We hypothesized that neutrophil modulation is an integral part of THP-mediated host protection. In a UTI model, THP-deficient mice showed elevated urinary tract bacterial burdens, increased neutrophil recruitment, and more severe tissue histopathological changes compared with WT mice. Furthermore, THP-deficient mice displayed impaired urinary NETosis during UTI. To investigate the effect of …


Biophysical Mapping Of Trem2-Ligand Interactions Reveals Shared Surfaces For Engagement Of Multiple Alzheimer's Disease Ligands, Jessica A Greven, Joshua R Wydra, Rory A Greer, Cynthia Zhi, David A Price, Jordyn D Svoboda, Christopher L M Camitta, Mya Washington, Daisy W Leung, Yuhua Song, Jen Alexander-Brett, Tom J Brett Jan 2025

Biophysical Mapping Of Trem2-Ligand Interactions Reveals Shared Surfaces For Engagement Of Multiple Alzheimer's Disease Ligands, Jessica A Greven, Joshua R Wydra, Rory A Greer, Cynthia Zhi, David A Price, Jordyn D Svoboda, Christopher L M Camitta, Mya Washington, Daisy W Leung, Yuhua Song, Jen Alexander-Brett, Tom J Brett

2020-Current year OA Pubs

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry. The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated …


Cancer-Related Health Behaviors During The Covid 19 Pandemic In Geographically Diverse Samples Across The Us, Breanna B Greteman, Bettina F Drake, Kia L Davis, Et Al. Jan 2025

Cancer-Related Health Behaviors During The Covid 19 Pandemic In Geographically Diverse Samples Across The Us, Breanna B Greteman, Bettina F Drake, Kia L Davis, Et Al.

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors. Our study assessed changes in cancer-related health behaviors during the pandemic, specifically physical activity, fruit/vegetable intake, smoking/tobacco use, and alcohol consumption.

METHODS: Eight cancer centers administered mailed/web-based/telephone surveys between June 2020 and March 2021. Surveys assessed demographics, perceptions on social distancing, and self-reported changes of behaviors (less/same/more) associated with cancer prevention or risk, e.g., physical activity, fruit/vegetable intake, tobacco/smoking use, and alcohol consumption. Descriptive analyses and logistic regression models assessed association of variables with behavior change. …


Full Issue, Volume 12, Number 3, Donna J. Peterson, Scott Cummings, Elizabeth Gregory North Jan 2025

Full Issue, Volume 12, Number 3, Donna J. Peterson, Scott Cummings, Elizabeth Gregory North

Journal of Human Sciences and Extension

No abstract provided.


Evaluation Of Tenecteplase In Patients With Acute Ischemic Stroke, Ithar Alsarraf, Rebecca Baker, Jennifer Pilotto, Emily Reich Jan 2025

Evaluation Of Tenecteplase In Patients With Acute Ischemic Stroke, Ithar Alsarraf, Rebecca Baker, Jennifer Pilotto, Emily Reich

Conference Presentation Abstracts

Purpose: As of January 2024, Corewell Health East hospitals updated their guidelines to include tenecteplase as the first line agent in the treatment of acute ischemic stroke. Tenecteplase is a high-risk medication, it is important to identify opportunities to improve its use and patient safety. This study aims to evaluate the appropriate usage and hemorrhagic events of tenecteplase in patients with suspected acute ischemic stroke according to Corewell Health Beaumont Troy Hospital guidelines. Methods: This was a single-center retrospective cohort study that evaluated adults age 18 years and older admitted to Corewell Health Beaumont Troy Hospital for acute ischemic stroke …


Evaluation Of Intravenous Surgical Prophylaxis Antibiotics Used In Colorectal And Hysterectomy Surgeries, Mehreen Hasan, Sandra Hartnagle, Sapna Shah Jan 2025

Evaluation Of Intravenous Surgical Prophylaxis Antibiotics Used In Colorectal And Hysterectomy Surgeries, Mehreen Hasan, Sandra Hartnagle, Sapna Shah

Conference Presentation Abstracts

Purpose: Colorectal and hysterectomy surgeries can expose patients to various bacterial organisms which can increase their risk of surgical site infections. The most common offending bacteria include Bacteroides fragilis, Escherichia coli, and other obligate anaerobes. Per the institution’s policy, cefazolin plus metronidazole is the preferred prophylactic antibiotic regimen in colorectal and hysterectomy surgeries. However, patient allergies or physician preference may lead towards utilization of alternative antibiotic therapy. This study will evaluate the number of patients who received antibiotics in accordance with the hospital guidelines, prior to colorectal and hysterectomy surgeries. Methods: This study will be a retrospective chart review including …


Customized Feminine Hygiene Wash Containing Postbiotics From Lactobacillus Spp. To Treat Urinary Tract Infections (Uti), Veena G. Nair Jan 2025

Customized Feminine Hygiene Wash Containing Postbiotics From Lactobacillus Spp. To Treat Urinary Tract Infections (Uti), Veena G. Nair

Theses and Dissertations

Probiotics, which support host health by maintaining normal microbial flora, offer a promising approach for preventing recurrent infections. To evaluate the prophylactic potential of vaginal probiotics against urinary tract infections (UTIs), we conducted a study on 54 healthy South Indian women aged 18–40 who visited the Obstetrics and Gynaecology outpatient clinic at Trichy SRM Medical College and Research Centre between June and July 2022. Vaginal swabs were collected following ethical guidelines, and commensal microbiota were isolated for probiotic characterization, with the broader objective of developing a customized feminine hygiene wash enriched with vaginal postbiotics.

Lactobacilli cell-free supernatant (CFS) demonstrated potent …


Nursing Knowledge Regarding Pap Smears For Transgender Men, Caytlin Capulong Jan 2025

Nursing Knowledge Regarding Pap Smears For Transgender Men, Caytlin Capulong

Nursing | Student Research Posters

Cervical cancer screening (CCS) is a crucial test used for preventative measures against cervical cancer, yet transgender men (TM) experience significantly lower screening rates in comparison to cisgender women due to pain, anxiety, and systemic healthcare barriers. A major factor for deterrence is pain during speculum insertion, often because of vaginal atrophy related to testosterone usage. Other factors include fear of discrimination, mistreatment, and lack of provider awareness, particularly among nurses who play a pivotal role in patient preparation and care. This research aims to assess the extent of nurses’ knowledge regarding Pap smears for female-to-male (FTM) patients through a …


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 Jan 2025

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 …


Measures Of Joint Kinematic Reliability During Repeated Softball Pitching, Erin Pletcher, Mita Lovalakar, Takashi Nagai, Chris Connaboy Jan 2025

Measures Of Joint Kinematic Reliability During Repeated Softball Pitching, Erin Pletcher, Mita Lovalakar, Takashi Nagai, Chris Connaboy

Department of Exercise Science Faculty Papers

Background/Objectives: Three-dimensional motion analysis is often used to evaluate improvements or decrements in movement patterns in athletes. The purpose of this study was to evaluate the reliability of joint flexion/extension angles of the pitching elbow and bilateral knees and hips in softball pitchers. Methods: Fourteen softball pitchers (17.9 ± 2.3 years) were tested in one session consisting of four sets of five consecutive fastballs and a second session of two sets of five fastballs. The magnitude of systematic bias and within-subject variation was calculated between pitches. An iterative intraclass correlation coefficient (ICC) process was used to determine intra- and inter-session …


Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay Jan 2025

Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive …


A Sequencing Overview Of Malignant Peripheral Nerve Sheath Tumors: Findings And Implications For Treatment, Kangwen Xiao, Kuangying Yang, Angela C Hirbe Jan 2025

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


Expanding Nucleic Acid-Encoded Medicine, Dafei Chai, Yong Li Jan 2025

Expanding Nucleic Acid-Encoded Medicine, Dafei Chai, Yong Li

Faculty, Staff and Students Publications

No abstract provided.


Exploring The Lived Experiences Of Persons Living With Hiv Who Are Homebound Due To One Or More Comorbidities Within A Southern State Using Photovoice, Anthony Alyn "Deek" Cunningham Jan 2025

Exploring The Lived Experiences Of Persons Living With Hiv Who Are Homebound Due To One Or More Comorbidities Within A Southern State Using Photovoice, Anthony Alyn "Deek" Cunningham

All ETDs from UAB

At the end of 2022, there were 1,109,418 adults and adolescents with HIV in the United States and the six dependent areas of American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, the Republic of Palau, and the US Virgin Islands (CDC, 2024). Due to ongoing advances in medications and treatments, people who have been diagnosed with HIV are living longer and healthier lives, making this a chronic health condition. Yet, there are gaps in the literature that focuses on this population growing older and aging in place. This dissertation investigated the lived experiences of individuals fifty years and older …


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. Jan 2025

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 Jan 2025

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 …


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 Jan 2025

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 …


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 Jan 2025

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 Jan 2025

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 Jan 2025

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 Jan 2025

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.


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 Jan 2025

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 …


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 Jan 2025

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 …


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 Jan 2025

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 …


Patient-Derived Xenografts Of Triple-Negative Breast Cancer Enable Deconvolution And Prediction Of Chemotherapy Responses, Jonathan T Lei, Lacey E Dobrolecki, Chen Huang, Ramakrishnan R Srinivasan, Suhas V Vasaikar, Alaina N Lewis, Christina Sallas, Na Zhao, Jin Cao, John D Landua, Chang In Moon, Yuxing Liao, Susan G Hilsenbeck, C Kent Osborne, Mothaffar F Rimawi, Matthew J Ellis, Varduhi Petrosyan, Bo Wen, Kai Li, Alexander B Saltzman, Antrix Jain, Anna Malovannaya, Gerburg M Wulf, Elisabetta Marangoni, Shunqiang Li, Daniel C Kraushaar, Tao Wang, Senthil Damodaran, Xiaofeng Zheng, Funda Meric-Bernstam, Gloria V Echeverria, Meenakshi Anurag, Xi Chen, Bryan E Welm, Alana L Welm, Bing Zhang, Michael T Lewis Jan 2025

Patient-Derived Xenografts Of Triple-Negative Breast Cancer Enable Deconvolution And Prediction Of Chemotherapy Responses, Jonathan T Lei, Lacey E Dobrolecki, Chen Huang, Ramakrishnan R Srinivasan, Suhas V Vasaikar, Alaina N Lewis, Christina Sallas, Na Zhao, Jin Cao, John D Landua, Chang In Moon, Yuxing Liao, Susan G Hilsenbeck, C Kent Osborne, Mothaffar F Rimawi, Matthew J Ellis, Varduhi Petrosyan, Bo Wen, Kai Li, Alexander B Saltzman, Antrix Jain, Anna Malovannaya, Gerburg M Wulf, Elisabetta Marangoni, Shunqiang Li, Daniel C Kraushaar, Tao Wang, Senthil Damodaran, Xiaofeng Zheng, Funda Meric-Bernstam, Gloria V Echeverria, Meenakshi Anurag, Xi Chen, Bryan E Welm, Alana L Welm, Bing Zhang, Michael T Lewis

Faculty, Staff and Students Publications

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to multiple single agents cannot be delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination. Combination responses were usually no better than the best single agent, with enhanced response in only ~13% of PDX, and apparent antagonism in a comparable percentage. Single-omic comparisons showed largely non-overlapping results between genes associated with single agent and combination treatments that …


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 Jan 2025

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 Jan 2025

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 …


Waste Clearance Shapes Aging Brain Health, Li-Feng Jiang-Xie, Antoine Drieu, Jonathan Kipnis Jan 2025

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.


Homecoming Mom Returns To Wise After Three Years Absence, Madelyn Lawrence Jan 2025

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.