Medicine and Health Sciences Commons^™

Evaluating The Effect Of Ethnicity And Amyloid On Gait Speed In The Healthy Aging Brain Study-Health Disparities Study, Alexandra M. Reed, Andrew Hooyman, Edward Ofori, Sydney Y. Schaefer

Physical Therapy Faculty Articles and Research

Background

Many novel Alzheimer's disease (AD) biomarkers have been studied in non-Hispanic White populations, despite Hispanic/Latino adults being 1.5 times more likely to develop AD and receiving a later diagnosis. Equitable, accessible assessments are needed to identify individuals at risk earlier. While cognitive screening monitors early AD signs, neuropsychological tests are often inequitable across ethnicity, race, and other social determinants of health. However, we have shown that performance-based motor assessments may be less susceptible to demographic factors than memory tests, and may be more equitable for screening older adults. Gait speed has been linked to elevated amyloid in non-Hispanic White …

Real-World Outcomes Of Talimogene Laherparepvec As Salvage Therapy For Advanced Melanoma, Melissa M Yamada, Smitha Chandrasekhar, Ted A Gooley, Rita E Chen, Coley Doolittle-Amieva, George Ansstas, Shailender Bhatia, Evan T Hall, Paul T Nghiem, Song Y Park, David Y Chen

2020-Current year OA Pubs

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories.

METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates.

RESULTS: Among …

Impact Of Physical Activity On Sleep In Adults Recovering From Substance Use Disorders: A Protocol For An N-Of-1 Observational Study, Sascha Thal, Cele Richardson, Joanne Mcveigh, Craig Thompson, Phoebe Wan, Bingyan Pang, Hugh Riddell, Stephen Bright, James Clarke, Bronwyn Myers

Research outputs 2022 to 2026

Introduction Sleep impairments are prevalent among individuals recovering from substance use disorders (SUDs) and are associated with poorer treatment outcomes and increased relapse risk. Physical activity (PA) is known to enhance sleep in general populations, but its day-to-day effects on sleep during SUD recovery remain underexplored, especially across different recovery stages. Methods and Analysis In this observational n-of-1 study, we aim to examine within-person associations between daily PA and sleep quality in three groups of individuals at varying stages of substance use recovery (early treatment, continuing care and long-term recovery). A substudy will validate the agreement between two wearable sleepmonitoring …

Benign Small Bowel Pneumatosis Intestinalis: Report Of A Rare Adverse Effect Of Tirzepatide, Kenneth Newcomer, Hani Soudah, Michael Beal, Thoi H Ngo

2020-Current year OA Pubs

No abstract provided.

Mental Health First Aid Certification's Impact On Filipino Nurses' Ability To Increase Personal Help-Seeking Behaviors, Self-Awareness Of Health Changes, And Improved Self-Connection, Maria Elena Holguin, Brenda Marshall, Faith Atte, Katherine J. Roberts

School of Nursing Faculty Scholarship and Creative Works

Background

Post COVID-19, almost 50% of nurses reported severe depression, and over 30% moderate to severe anxiety. Nurses from minority racial and ethnic backgrounds, including Filipino nurses, accounted for more than 54% of COVID-related deaths, despite comprising only 24.1% of the nursing workforce. Filipino nurses, making up only 1% of the U.S. population, comprise 4.5 % of the nursing workforce and face significant barriers to seeking mental health services, including stigma, a sense of shame, and adherence to cultural values that view mental illness as unacceptable.

Aim 

To assess the impact of Mental Health First Aid (MHFA) certification among Filipino …

Lost In Translation: How Health Literacy Impacts Pharmaceutical Transactions From Healthcare Professionals To Patients, Grace Nwaege

2025 Fall Honors Capstones Projects - Archive

Health literacy is a core element of public health, involving the ability to access, understand, evaluate, and use information to maintain well-being. In the United States, it aligns with an average reading level of about an eighth grader, which continues to decline over time. As pharmacists serve as the final point of contact in most outpatient settings, their ability to communicate effectively at this literacy level is crucial. This study examines how pharmacies address this challenge using qualitative methods, including health literacy assessments of patient consent forms and stakeholder interviews with pharmacy technicians about resource use. Findings show materials higher …

Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …

Too Much Of A Good Thing: Otc Calcium Carbonate Overdose Causing Milk-Alkali Syndrome In A Psychiatric Patient., Alexandra She, Sangay Bhutia, Francis Jenney

PCOM Scholarly Works

BACKGROUND: In the United States, milk-alkali syndrome or calcium-alkali syndrome is the third most common cause of hypercalcemia, after primary hyperparathyroidism and malignancy. Clinically, patients present with a triad of hypercalcemia, acute kidney injury, and metabolic alkalosis. Classically, it has been associated with excessive intake of calcium and absorbable alkali, and recently it has become more common in postmenopausal females who ingest calcium supplements for osteoporosis.

CASE PRESENTATION: Here, we present the case of a 72-year-old Caucasian female with a longstanding diagnosis of bipolar I disorder who presented to the Emergency Department (ED) with a sudden onset of generalized weakness, …

Surgical Treatment Of Post-Traumatic Elbow Stiffness In Pediatric Patients: A Systematic Review And Meta-Analysis, Roya Khorram, Areeb Ahmad, Reza Vafadar, Ronald Joseph Shamus, Surena Namdari, G. Russell Huffman, Amir R. Kachooei

Rothman Institute Papers

BACKGROUND: Post-traumatic elbow stiffness (PTES) has been reported in up to 21% of pediatric patients following elbow fractures and can profoundly compromise a child's function, and independence. The primary surgical approaches include open and arthroscopic arthrolysis, both of which have demonstrated improvements in range of motion (ROM) and functional scores. This systematic review and meta-analysis aims to compare the effectiveness, ROM, and complication rates between open and arthroscopic release in pediatric patients with PTES.

METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilized to conduct a systematic review and meta-analysis on surgical treatment for PTES. Comprehensive …

Using A Heuristic Tool To Improve Symptom Self-Management In Adolescents And Young Adults With Cancer: Protocol For A Randomized Controlled Trial., Suzanne Ameringer, Grace Hodges, R K Elswick, Lauri Linder, Catherine Fiona Macpherson, Kristin Stegenga

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYAs) with cancer experience multiple distressing symptoms during treatment, yet few developmentally relevant resources have been developed to help them self-manage their symptoms. Empowering patients to have a more active role in self-management during cancer treatment may lessen their symptom severity and distress.

OBJECTIVE: The aim of this study is to test an intervention designed to improve symptom self-management, the Computerized Symptom Capture Tool (C-SCAT), by helping AYAs understand their unique symptom experience and discuss it with their health care providers.

METHODS: We are conducting a multisite, 2-group randomized controlled trial to evaluate the effects …

Evaluating The Impact Of A Community-Based Prostate Cancer Screening Program, Amy Leader, Kristine Pham, Nicola Cianci, Hannah Knapp, Fatuma Doka, Suzanne Barron, Oleksandr Kolesnikov, Jordan Dehoratius, Katie Bradley, Le'ann Robles, Robert Giamboy, Olivia Dahlgren, Leonard G. Gomella

Kimmel Cancer Center Faculty Papers

BACKGROUND: One out of eight men in the U.S. will be diagnosed with prostate cancer during his lifetime. Black men are more likely to be diagnosed with and die from prostate cancer than other males, contributing to significant prostate cancer disparities. Early detection, often by routine screening, allows for more options for treatment and an increased chance of survival. Barriers to screening contribute to prostate cancer disparities, particularly among those who lack regular access to health care. Community based screening programs may overcome barriers to prostate cancer screening.

METHODS: An urban, NCI-designated cancer center collaborated with a national prostate cancer …

Intraventricular Iron Causes Severe Hydrocephalus – A Model Of Severe Neonatal Hydrocephalus, Kwang-Min Kim, Arokoruba Oboba Cheetham-West, Mohamed Rafiuddin Ahmed, Megan Phillips, Andrey V Malkovskiy, Venkata Raveendra Pothineni, Kyle D Brewer, Chirag B Patel, Jayakumar Rajadas, Kelly B Mahaney

Faculty, Staff and Student Publications

Background: Neonatal germinal matrix hemorrhage-intraventricular hemorrhage and subsequent post-hemorrhagic hydrocephalus (PHH) is a leading cause of neurologic morbidity and mortality in preterm infants. Preclinical models of PHH have implicated hemoglobin and iron-mediated cellular injury in the pathogenesis of PHH, but have typically demonstrated a phenotype characterized by mild to moderate ventriculomegaly – the equivalent of which may not even require intervention in the human condition. We sought to establish a preclinical model of severe IVH that recapitulates the severity of the hydrocephalus phenotype requiring neurosurgical intervention and to determine the causal blood degradation product resulting in severe hydrocephalus following preterm …

Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju

Faculty, Staff and Student Publications

No abstract provided.

Phospholipid Scramblase 1 (Plscr1) Regulates Interferon-Lambda Receptor 1 (Ifn-Λr1) And Ifn-Λ Signaling In Influenza A Virus (Iav) Infection, Alina Xiaoyu Yang, Lisa Ramos-Rodriguez, Parand Sorkhdini, Dongqin Yang, Carmelissa Norbrun, Sonoor Majid, Sanghyun Lee, Yong Zhang, Michael Holtzman, David F Boyd, Yang Zhou

2020-Current year OA Pubs

Phospholipid scramblase 1 (PLSCR1) is an interferon-stimulated gene (ISG) that has several known anti-influenza functions. However, the mechanisms in relation to its expression compartment and enzymatic activity have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections. Our results showed that influenza A virus (IAV)-infected

Development And Evaluation Of The Agitation In Alzheimer's Screener For Caregivers (Aasc): A Clinical Tool To Screen For Agitation., Carolyn Clevenger, W Clay Jackson, Jared Stroud, Malaak Brubaker, Mehul Patel, Iwona Bucior, Emily Bratlee-Whitaker, T Michelle Brown, Sheri Fehnel, Sue Peschin, Jeffrey Cummings, George Grossberg

Ambulatory and Primary Care Articles

OBJECTIVE: Although agitation is a common neuropsychiatric symptom in Alzheimer's dementia, it can be challenging to recognize and diagnose. Caregivers of individuals with Alzheimer's dementia are often the first to encounter agitation behaviors but may struggle to recognize and communicate symptoms to healthcare professionals (HCPs). Here, we describe the development and evaluation of the Agitation in Alzheimer's Screener for Caregivers (AASC), a practical screening tool to identify agitation symptoms and facilitate caregiver-HCP communication.

METHODS: The AASC was developed based on the International Psychogeriatric Association (IPA) criteria for agitation in cognitive disorders, input from multidisciplinary experts, and qualitative interviews with caregivers …

Stimulant Medications Affect Arousal And Reward, Not Attention Networks, Benjamin P Kay, Muriah D Wheelock, Ryan V Raut, Roselyne J Chauvin, Athanasia Metoki, Aishwarya Rajesh, Andrew Eck, Jim Pollaro, Anxu Wang, Vahdeta Suljic, Babatunde Adeyemo, Noah J Baden, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Nadeshka Ramirez-Perez, Samuel R Krimmel, Anita Randolph, Jarod L Roland, Ginger E Nicol, Timothy O Laumann, Scott Marek, Evan M Gordon, Marcus E Raichle, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Prescription stimulants (e.g., methylphenidate) are thought to improve attention, but evidence from prior fMRI studies is conflicted. We utilized resting-state fMRI data from the Adolescent Brain Cognitive Development Study (n = 11,875; 8-11 years old) and validated the functional connectivity findings in a precision imaging drug trial with highly sampled (n = 5, 165-210 min each) healthy adults (methylphenidate 40 mg). Stimulant-related connectivity differences in sensorimotor regions matched fMRI patterns of daytime arousal, sleeping longer at night, and norepinephrine transporter expression. Taking stimulants reversed the effects of sleep deprivation on connectivity and school grades. Connectivity was also changed in salience …

A Phase-Ii Randomized Controlled Pilot And Feasibility Study Of Nicotinamide Riboside Supplementation In Older Adults With Amnestic Mild Cognitive Impairment, Christopher R. Martens, Kevin P. Decker, Theodore M. Deconne, Faria Sanjana, Fiona Horvat, Nicholas A. Rizzi, Catherine Awad, Elizabeth Habash, Joshua C. Hobson, Michael L. Armstrong, Nichole Reisdorph, Ryan T. Pohlig, Alyssa M. Lanzi, Curtis L. Johnson, Matthew L. Cohen, James M. Ellison

Department of Psychiatry and Human Behavior Faculty Papers

Abstract

Background

The decline of nicotinamide adenine dinucleotide (NAD+) with aging may elevate risk of Alzheimer’s disease and related neurocognitive disorders (ADRD) by impairing cellular energy metabolism and reducing cerebral blood flow.

Method

We conducted a 12-week double-blind, randomized, placebo-controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD+ precursor, nicotinamide riboside (NR; 500 mg b.i.d.), for enhancing cognitive function and cerebral perfusion in older adults with mild cognitive impairment (MCI).

Result

52 participants (33 females, 19 males) were randomized and 42 completed the trial (NR = 22, placebo = 20). Adherence was similar between groups …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Light-Induced Oslike1 Phosphorylation Enhances Rice Resistance Against Blast Disease, Jiangtao Liu, Lei Su, Wenya Wang, Jintao Wang, Weizhong Chen, Zhixiang Yang, Leiyun Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Zhongqiang Qi, Yongfeng Liu, Yuqiang Liu, Ping Wang, Muxing Liu, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Rice blast caused by Magnaporthe oryzae poses a major threat to world food supply. Conditions conducive to the disease include insufficient light. Our previous studies found that light-dependent phosphorylation of light-harvesting complex II protein (LHCB5) mediates rice immunity; however, the underlying mechanisms, in particular, the upstream regulators of LHCB5 phosphorylation, remain unknown. Here, we show that OsLIKE1 functions as a lectin receptor-like kinase (LecRLK) to play a critical role in rice resistance against M. oryzae. OsLIKE1 interacts with and phosphorylates LHCB5. In addition, we find two phosphorylation sites in the kinase domain of OsLIKE1 important for its auto-phosphorylation and phosphorylation …

Synergistic Effects Of Gfap With Tnfr1 And Tnfr2 On Conversion To Ad Dementia And Overall Survival Across The Alzheimer’S Disease Spectrum, Laura Alejandra Ramirez Tirado, Ann D. Cohen, C. Elizabeth Shaaban, Cristy Matan, Brian J. Lopresti, Milos D. Ikonomovic, Thomas K. Karikari, Victor L. Villemagne, Oscar L. Lopez

Department of Neurology Faculty Papers

Background: We recently reported synergistic effects of TNFR1 and TNFR2 with
astrogliosis resulting in greater vascular burden and neurodegeneration, particularly in
Aβ+ participants. Here, we aimed to assess the interactions of peripheral inflammation
and astrogliosis on incidence of AD dementia and mortality. We hypothesized
synergistic effects with astrogliosis resulting in increased incidence of dementia, and
mortality, particularly in Aβ+ participants.
Methods: Participants of the Gingko evaluation of memory (GEM) study underwent
PiB-PET scans between 2009-2018. GFAP and peripheral inflammatory markers were
measured in 2009 by immunoassay. We evaluated the relationship of peripheral
markers of inflammation (TNFR1,TNFR2) and astrogliosis (GFAPdementia incidence …

The Role Of Reproductive Aging And Surgeries For Alzheimer’S Disease And Related Dementias (Adrd) Diagnoses In The Cardiovascular Health Study, Alexis Reeves, Oscar L. Lopez, Michelle D. Shardell, Hoda S. Abdel Magid, C. Elizabeth Shaaban, Michelle C. Odden

Department of Neurology Faculty Papers

Abstract

Background

Most US individuals with ADRD are women. Menopause typically occurs in midlife, accompanied by declines in potentially neuroprotective and cardioprotective hormones. Earlier menopause leads to earlier exposure to decreased sex hormones, potentially increasing ADRD risk. Surgical menopause via reproductive surgeries may cause a sudden loss of hormones and may represent be a modifiable risk factor for ADRD. We aimed to determine if menopausal type and age are associated with physician adjudicated-ADRD diagnoses.

Methods

Data were from 3371 women prospectively followed from age 65+ years. Participants self-reported age of menopause and/or surgeries, hormone-therapy, education, and race (Black/White). For this …

A Tissue Renewal-Based Mechanism Drives Colon Tumorigenesis, Ryan M. Boman, Gilberto Schleiniger, Christopher Raymond, Juan P. Palazzo, Anne Shehab, Bruce M. Boman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Our Goal is to identify how colorectal cancer (CRC) arises in the single-layered cell epithelium (simple columnar epithelium) that lines the luminal surface of the large intestine. Background: We recently reported that the dynamic organization of cells in colonic epithelium is encoded by five biological rules and conjectured that colon tumorigenesis involves an autocatalytic tissue renewal reaction. Introduction Our objective was to define how altered crypt turnover explains tissue disorganization that leads to adenoma morphogenesis and CRC. Hypothesis: Changes in rate of tissue renewal-based cell polymerization leads to epithelial expansion and tissue disorganization during adenoma histogenesis. Methods: Accordingly, we created …

Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang

Faculty, Staff and Students Publications

Determining tumor-specificity of MHC-bound peptides is crucial for cancer immunotherapy development, yet current methods struggle with class II peptides and non-reference sequences. We introduce PepQueryMHC, an ultra-fast tool that integrates MHC-bound peptide sequences with translated RNA-seq reads for efficient tumor antigen prioritization. We demonstrate its versatility in prioritizing class I and II tumor antigens, mapping the cellular origins of presented peptides, and resolving uncertainties surrounding the prevalence of proteasome-spliced peptides.

Sox11 Modulates Bcr Signaling Through The Pax5/Cd19 Axis For Therapeutic Targeting In Btk-Resistant Mantle Cell Lymphoma, Rudra Prasad Dutta, Heng-Huan Lee, Violetta V Leshchenko, Ravi Prakash Shukla, Fangfang Yan, Yang Liu, H Ümit Kaniskan, Xing Qiu, Jian Jin, Lapo Alinari, Michael Wang, Samir Parekh

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is an incurable subtype of B-cell non-Hodgkin lymphoma. Despite multiple approved Bruton tyrosine kinase inhibitors (BTKis), resistance to BTKi continues to pose a major clinical challenge. The transcription factor sex determining region Y-box 11 (SOX11) is expressed in most patients with MCL and is associated with poor outcomes. We have previously demonstrated SOX11-dependent B-cell receptor (BCR) signaling in transgenic models of MCL. Here, we report that SOX11 drives BCR signaling via the transcriptional activation of the PAX5/CD19 axis. The translational potential of these results is significant as single-cell RNA sequencing data show that SOX11 is overexpressed …

Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie

Faculty, Staff and Student Publications

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7-14 days of age, designated "transitional ages," as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …

Ribosomal Protein Control Of Hematopoietic Stem Cell Transformation Through Regulation Of Metabolism, Bryan Harris, Stephen Sykes, Et Al.

2020-Current year OA Pubs

We report here that expression of the ribosomal protein RPL22 is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), and reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from altered metabolism, including increased fatty acid oxidation (FAO) and a striking induction of the stemness factor Lin28b in the resulting leukemia. Lin28b promotes a substantial increase in lipid …

Esat-6 And Cfp-10 Reactive Igg In Patients With Tuberculosis Inhibits Intracellular Bacteria, Joshua R. Miles, Pei Lu, Shuangyi Bai, Genesis P. Aguillón-Durán, Javier E. Rodríguez-Herrera, Bronwyn M. Gunn, Blanca I. Restrepo, Lenette L. Lu

School of Medicine Publications

Perspectives beyond the CD4 T cell interferon (IFN)-γ paradigm are needed to understand immunity in tuberculosis (TB). Growing data in patients across a spectrum of TB highlight that changes in antibody Fc domain glycosylation and Fc effector functions correlate with disease and impact Mycobacterium tuberculosis (Mtb) infection. How antigen-specific antibodies within polyclonal responses affect bacteria is less clear. This study examines antibodies targeting ESAT-6 and CFP-10, Mtb virulence proteins essential for pathogenesis. Data from patients with TB show that polyclonal immunoglobulin (Ig)G reactive to ESAT-6 and CFP-10 diverges from other Mtb and non-Mtb antigens with enhanced sialylation, …

Liberal Or Restrictive Postoperative Transfusion In Patients At High Cardiac Risk: The Top Randomized Clinical Trial, Panos Kougias, Sherene E Sharath, Min Zhan, Jeffrey L Carson, L Erin Norman, Zhibao Mi, Rupsi Pal, Hasan Dosluoglu, J Gregory Modrall, George A Sarosi, Peter Nelson, Shipra Arya, Alexandra Scrymgeour, Jade Ollison, Lawrence A Calais, Vijay Nambi, L Parker Gregg, Shuaib M Abdullah, Shirling Tsai, Natasha Becker, Justin C Choi, Louisa Chiu, Salvatore Scali, Neal R Barshes, Samir Awad, Mohammed Moursi, Matthew C Koopmann, Mitchell Sally, Daniel Ihnat, Archana Ramaswamy, Warren Gasper, Edith Tzeng, Mark A Wilson, Gale Tang, Grant Huang, Kousick Biswas

Faculty, Staff and Students Publications

Importance: Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear.

Objective: To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia.

Design, setting, and participants: This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac …