Medicine and Health Sciences Commons^™

Bottlebrush Polymer Conjugates For Enhanced Antisense Oligonucleotide Therapy In Myotonic Dystrophy Type 1, Yao Li, Gyu Seong Heo, Yongjian Liu, Et Al.

2020-Current year OA Pubs

Oligonucleotides are a promising class of genetic medicine for myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy. However, poor muscle distribution of nucleic acid drugs following systemic administration has hindered drug development, and no curative treatment currently exists. DM1 pathology requires drug localization to the nucleus, where pathogenic mutant RNA is sequestered, posing additional challenges after cellular internalization regarding endosomal escape and nuclear uptake. Here, we show that a locked nucleic acid oligonucleotide targeting mutant CUG repeat RNA tracts, conjugated to a bottlebrush polymer, exhibits improved muscle distribution and potent correction of DM1-associated splicing dysregulation in a …

Chiari Malformation Type 1 Is Associated With A Smaller Fourth Ventricle Volume - A Multi-Cohort Replication Study, Jarod L Roland, Thanda Meehan, Alexandra Gabliani, Scott Marek, Nico Dosenbach, Joshua S Shimony, Nilay Jakati, Yi Li, Leo Sugrue, Jennifer M Strahle, Chenyang Lu, David D Limbrick, Gabe Haller

2020-Current year OA Pubs

Chiari Malformation Type 1 (CM1) is canonically defined by ectopic position of the cerebellar tonsils with additional anatomic variations described inconsistently. Effect on fourth ventricle volume is controversial with prior studies reporting disparate results and methodologically limited to single institution series that hinder generalizability. This limitation was addressed utilizing multiple data sources, longitudinal replication, and reproducible methods using both FreeSurfer and the deep learning-based DL+DiReCT tools for automated volumetrics. First, we analyzed a local retrospective clinical cohort of individuals with CM1 and controls. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we analyzed volumes at baseline then replicated …

Prmt5 As A Key Driver Of Stemness And Metastatic Potential In Triple-Negative Breast Cancer, Jae Jin Jeong, Mauli Maniar, Shahrzad Ghane, Sakshi Deshpande, Claire Ellis, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5-KLF4 axis results in …

The Transitional Liver Clinic: Study Protocol For A Stepped-Wedge Cluster Randomized Trial, Lindsay Yoder, Elliot B. Tapper, Richard S. Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S. Orman

Einstein Health Papers

BACKGROUND: Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.

METHODS: This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention …

Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”¹ Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.

METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …

Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas

Faculty, Staff and Students Publications

Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …

Early Adoption Of Thyroid Radiofrequency Ablation In Canada: Physician Experiences, Barriers, And Facilitators To Implementation, Harrison Gao, David Liu, Ben B. Levy, Justin Shapiro, Kevin M. Higgins, Diana E. Khalil, Elizabeth E. Cottrill, Courtney Poon, Pabiththa Kamalraj, Justine Philteos, Antoine Eskander

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

IMPORTANCE: Thyroid radiofrequency ablation (RFA) is a minimally invasive alternative to surgery for thyroid nodules. Despite strong international evidence, thyroid RFA was only approved by Health Canada in April 2023. Understanding the experiences of early adopters can inform the broader adoption of RFA in Canada and other healthcare systems.

OBJECTIVE: To describe the implementation experiences of early adopters of thyroid RFA in Canada and identify barriers and facilitators to adoption.

DESIGN: Multiple methods.

SETTING: All 8 listed RFA facilities in Canada.

PARTICIPANTS: Physicians performing thyroid RFA (n = 9).

MAIN OUTCOME MEASURES: Survey and semi-structured interviews.

RESULTS: Most participants reported …

Non-Tobacco Nicotine Dependence Is Associated With Increased Complications Following Clavicle Open Reduction Internal Fixation, Akin A. Adio, Rahul K. Goyal, Abby Skiena, Mohammad Daher, John G. Horneff, Hafiz F. Kassam, Brian W. Hill, Joseph A. Abboud

Rothman Institute Papers

BACKGROUND: Tobacco dependence is well established to impair bone healing and increase postoperative complications. However, the independent effects of nicotine, separate from combustion-related factors, remain unclear. This study aimed to evaluate the impact of non-tobacco nicotine dependence (NTND) following open reduction and internal fixation (ORIF) of clavicle fractures, including midshaft and lateral fracture subtypes.

METHODS: A retrospective cohort study was performed using a large national database. Patients undergoing ORIF of clavicle fractures were identified using procedural and diagnostic codes. Patients with non-tobacco nicotine dependence (e.g., vaping, patches, or gum) were identified and propensity score matched to (1) patients without nicotine …

Intrathecal (G4c2)149 Delivery In C9orf72-Deficient Mice Yields Mild Motor Dysfunction And Als/Ftd Pathological Hallmarks, Katelyn Russell, Amelia Shahrabi, Suleyman Akerman, Matthew D. Byrne, Jeffrey Rothstein, Davide Trotti, Brigid Jensen, Aaron Haeusler

Farber Institute for Neuroscience Faculty Papers

A repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet existing mouse models incompletely engage spinal regions implicated in disease. Here, an adeno-associated virus encoding (G4C2)149 repeats was delivered via neonatal intrathecal injection, achieving widespread CNS expression with robust spinal cord targeting. This approach was applied to mice with graded loss of endogenous C9orf72 to interrogate both gain- and loss-of-function mechanisms. Longitudinal motor, behavioral, and pathological analyses revealed that repeat expression primarily drives mild, progressive muscle weakness, whereas coordination deficits were largely genotype dependent. Subtle gait abnormalities and hyperactivity …

Sputum Lautropia Is Decreased In Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Brendan Allen, J. Kirk Harris, Kristine A. Kuhn, Kevin D. Deane, Stephen M. Humphries, Joyce S. Lee, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

OBJECTIVE: To investigate whether lung microbial composition differs between individuals with rheumatoid arthritis and pulmonary fibrosis (RA-PF) compared to those without fibrosis (RA-no-PF).

METHODS: We enrolled 54 RA patients (22 RA-PF, 32 RA-no-PF) from rheumatology and pulmonary clinics. PF was defined by high-resolution computed tomography (HRCT) findings. Induced sputum was analyzed using 16 S rRNA sequencing to identify the relative abundance of sputum bacteria. Taxonomic differences between groups were evaluated using three independent analytic approaches: Mann-Whitney U, DESeq2, and EdgeR, with false discovery rate correction. Logistic regression examined associations between Lautropia abundance and clinical variables.

RESULTS: Individuals with RA-PF were …

Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …

Automated Alerts To Improve Timely Evaluation And Treatment Of Valvular Heart Disease: The Alert Trial., Wayne B Batchelor, Brian R Lindman, Megan Coylewright, Antoine Keller, Brody Wehman, Adnan Chhatriwalla, Sandeep M Patel, Kevin Stiver, Firas Zahr, Miguel Sotelo, Dongho Shin, Chris Rogers, Graeme L Hickey, Jamie Williams, Myra Fan, Sreekanth Vemulapalli

Medical Education Articles

BACKGROUND: Severe aortic stenosis (AS) and mitral regurgitation (MR) are frequently undertreated and characterized by persistent sex, racial and ethnic, socioeconomic, and geographic disparities despite effective valve therapies. Whether automated electronic clinician notification (ECN) alerts improve the evaluation and treatment of AS and MR across health systems is unknown.

OBJECTIVES: The purpose of this study was to evaluate whether ECN alerts improve guideline-directed evaluation and treatment of significant AS and MR across multiple health systems.

METHODS: ALERT is a multisystem, cluster-randomized clinical trial including clinicians ordering echocardiograms across 5 U.S. health systems encompassing 35 hospitals between August 2024 and September …

Electronic Health Record Alerts To Improve Lipid Lowering After A Recent Myocardial Infarction, Dean G. Karalis, Benjamin Richter, Scott Hessen, Patrick Moeller, Laney K. Jones

Division of Cardiology Faculty Papers

BACKGROUND: This observational, quality initiative evaluated the impact of changing from a passive (dismissible) to an active (nondismissible without action) electronic health record alert on guideline-recommended lipid-lowering therapy (LLT) prescriptions in patients with recent myocardial infarction at risk for secondary events.

METHODS: We sequentially recruited a retrospective passive-alert (February 2018-July 2019; n=733) and a prospective active-alert (August 2020-January 2022; n=587) cohort of patients who triggered an alert to intensify LLT or order a low-density lipoprotein-cholesterol (LDL-C) test if they had a recent myocardial infarction (within 12 months) and elevated (≥70 mg/dL) or missing LDL-C. Prescribed LLTs and cumulative percentages of …

Hp1bp3 Loss Links Chromatin Reorganization To Metabolic Vulnerability In Glioma, Brittney Lozzi, Taylor A Gatesman, Pushan Dasgupta, Debosmita Sardar, Yeunjung Ko, Chenyu Mao, Hsiao-Chi Chen, Rachel N Curry, Dongjoo Choi, Carrie A Mohila, Melissa L Bondy, Ganesh Rao, Marco Gallo, Sameer Agnihotri, Benjamin Deneen

Duncan NRI Faculty and Staff Publications

High-grade gliomas (HGGs) are aggressive brain tumors with poor prognosis, driven in part by metabolic and epigenetic adaptations. Methionine metabolism supports HGG growth by supplying S-adenosylmethionine for methylation reactions, yet how nutrient availability influences chromatin organization in HGG remains incompletely understood. Using an immunocompetent mouse model of HGG, we found that dietary methionine restriction reduced tumor proliferation, extended survival, and induced partial nuclear inversion. We identified Hp1bp3 as a key regulator of tumor growth that functions by interacting with nuclear tethering proteins to mediate chromatin reorganization. Loss of Hp1bp3 results in the upregulation of histone demethylases leading to selective depletion …

Broadly Reactive Human Monoclonal Antibodies Targeting Influenza A Nucleoprotein Lack Protective Activity In Vivo, Walter N Harrington, David C Brice, Aaron J Schmitz, Jackson S Turner, Rafael Brent, Philip A Mudd, Ali H Ellebedy, Richard J Webby

2020-Current year OA Pubs

The antibody response to influenza virus infection targets numerous viral proteins, with those specific for the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins being the most extensively studied. Antibodies to HA and NA function as independent immune correlates of protection and form the basis of most vaccine approaches. In contrast, the contribution of antibodies to other viral proteins such as the nucleoprotein (NP) remains unclear, and existing studies have reached conflicting conclusions. In this work, we examined three human monoclonal NP antibodies isolated from plasmablasts of two individuals naturally infected with influenza A virus (IAV) during the 2018-2019 influenza season. …

Macropinocytosis Inhibition Attenuates Profibrotic Responses In Lung Fibroblasts And Pulmonary Fibrosis Models, Ivan O Rosas, Aaron K Mcdowell-Sanchez, Santiago Sanchez, Juan D Cala-Garcia, Alan R Waich Cohen, Elisa Ruiz-Echartea, Scott A Ochsner, Daniel C Kraushaar, Lindsay J Celada, Dandan Sun, Francesca Polverino, Cristian Coarfa, Neil J Mckenna, Konstantin Tsoyi

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in experimental pulmonary fibrosis models. We found that macropinocytosis is increased in human lung fibroblasts (HLFs) derived from patients with IPF. The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs and reduced pulmonary fibrosis in bleomycin-injured (Bleo-injured) mice. EIPA exerted its antifibrotic effects by regulating amino acid uptake, mammalian target of rapamycin complex 1 …

Autophagic Flux Blockade Under Hypocapnia Reveals Co2-Sensitive Regulation Of Autophagy-Lysosome Homeostasis, Naghmana Ashraf, Zhen Sun, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

Hypocapnia, a reduction in partial pressure of carbon dioxide (CO2), commonly occurs in clinical contexts such as mechanical ventilation, panic disorder, and brain injury, yet its impact on cellular homeostasis remains poorly understood. Given the central role of autophagy in stress adaptation, we investigated how low CO2 influences autophagic flux and lysosomal function. We found that hypocapnia induces autophagosome accumulation while impairing cargo degradation, indicating a blockade in autophagic flux. This response was accompanied by increased lysosome biogenesis but, paradoxically, reduced autophagosome-lysosome fusion and lysosomal proteolytic activity. Mechanistically, hypocapnia promoted TFE3 dephosphorylation and nuclear translocation, driving transcriptional activation of lysosomal …

Ultrasound-Enabled Refreshable Electrochemical Sensors For Cardiac Biomarker Monitoring, Mayank Garg, Heng Guo, Myeong Namkoong, Elizabeth Zhanov, Connor Malone, Md Saifur Rahman, Ayse Akcan-Arikan, Limei Tian

Faculty, Staff and Students Publications

Cardiac troponin I (cTnI) is the gold-standard biomarker for acute myocardial infarction, yet current laboratory-based high-sensitivity assays require centralized infrastructure, trained personnel, and serial testing, limiting their suitability for real-time or continuous monitoring in resource-limited settings. Point-of-care electrochemical sensors have shown promise for rapid cTnI detection, but their reliance on antibodies as biorecognition elements and redox mediator solutions, and single-use operation restricts practical translation. Here, we report an ultrasound-enabled refreshable electrochemical biosensor for sensitive, stable, and repeatable cTnI monitoring. The device employs a cTnI-specific peptide as the biorecognition element, providing enhanced stability during storage, transport, and operation. Label-free electrochemical impedance …

Healthcare Experiences And Needs Of Patients With Pregnancy Of Unknown Location: A Qualitative Study, Kavita Vinekar, Zahava Shimshi, Amanda Doty, Samantha Kolowrat, Rebecca Mercier, Agatha Berger, Kristin L. Rising

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: Patients presenting with bleeding or pelvic pain in early pregnancy are commonly found to have pregnancies of unknown location (PUL), with no sonographic findings of intrauterine nor ectopic pregnancy. We aimed to explore healthcare experiences and needs of patients presenting with PUL.

METHODS: This was a qualitative study using semi-structured interviews to explore healthcare experiences among patients with PUL. Patients were eligible if they presented with bleeding or abdominopelvic pain to the OB/GYN office or emergency department and were found to have a PUL followed in an electronic health record tracking list; had an initial human chorionic gonadotropin (hCG) …

Glycosphingolipids Regulate Phosphatidylserine Transport Machinery That Operates At Er-Pm Contact Sites, Ritchel Gannaban, Sher Ali, Wei Chen, Melanie Nguyen, Li Lai, Travis I Moore, Yubin Zhou, John F Hancock, Junchen Liu

The Brown Foundation: Institute of Molecular Medicine

Plasma membrane (PM) localization of KRAS requires specific glycosphingolipids in the outer leaflet and phosphatidylserine (PS) in the inner leaflet. PM PS content is controlled by lipid transport proteins ORP5 and ORP8, which operate at ER-PM membrane contact sites (MCSs). Using high-resolution imaging, we now show that GSLs, including GM3 and SM4, are required to maintain ORP5 and ORP8 localization to MCSs. Genetic deletion or pharmacologic inhibition of enzymes required for the biosynthesis of GM3 or SM4 displaces PI4-kinase Type IIIα (PI4KIIIα) and its adaptor EFR3A from the PM, thereby reducing PM phosphatidylinositol 4-phosphate (PI4P) content. PM interactions of ORP5 …

Apolipoprotein B100 Predicts Cardiovascular And Limb Events In Type 2 Diabetes Patients With Chronic Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population.

METHODS: In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12 months with visits at 1, 3, 6, and 12 months post-procedure. …

Identifying Social Determinants Of Health Subgroups And Their Associations With Health Outcomes In A Prospective Us Adult Covid-19 Cohort: An Analysis Of The Inspire Registry, Yohali Burrola-Mendez, Eugene Lin, Canada Parrish, Chialing Hsu, Mandy J. Hill, Michael Gottlieb, Kristin L. Rising, Lauren E. Wisk, Nicole L. Gentile, Rachel E. Geyer, Robert A. Weinstein, Michelle Santangelo, Kristyn Gatling, Jonathan W. Dyal, Joann G. Elmore, Robert M. Rodriguez, Phillip Watts, Ji Chen, Zihan Diao, Erica S. Spatz, Kwun Cg Chan, K A. Stephens, Kelli N. O'Laughlin, Inspire Group

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

DESIGN: Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

SETTING: Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and …

Patterns Of Brain-Wide Associations Reflect Socioeconomics, Scott Marek, Meghan Rose Donohue, Nicole R Karcher, Caroline P Hoyniak, Roselyne J Chauvin, Ashley C Meyer, John Miller, Andrew N Van, Anxu Wang, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Samuel R Krimmel, Athanasia Metoki, Rebecca F Schwarzlose, Steven E Petersen, Joan Luby, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Previous brain-wide association studies (BWAS) have linked specific environmental and behavioral variables to brain variability. In this work, we mapped 649 variables to children's brains and compared the resultant BWAS maps with each other and with neurobiological reference patterns. Socioeconomic status (SES) showed the strongest brain-wide associations. The SES associations were strongest in motor and sensory but not cognitive regions, a pattern shared across many BWAS maps, including intelligence quotient (IQ). A single, common BWAS brain pattern existed across variables that was most reflective of a child's socioeconomics. Adjusting for SES weakened brain-IQ associations, eliminating the BWAS motor and sensory …

Cryoneurolysis Of Auriculotemporal Nerve For Treatment Of Otalgia, Nikit Patel, Shireen Rabiei, Daniel Moon, Yevgeniya Sergeyenko

Moss-Magee Rehabilitation Papers

Otalgia in adults is often secondary to non-otologic pathology, particularly with normal otoscopic examination. Auriculotemporal neuralgia (ATN) is a rare and overlooked cause of secondary otalgia. We present a case of an Army veteran with chronic right otalgia and dizziness following blast-related mild traumatic brain injury who was initially diagnosed with vestibular migraine. Despite significant improvement in headache symptoms with migraine-directed preventive and abortive treatments, otalgia persisted. Auriculotemporal nerve block produced complete but short-lived pain relief, confirming ATN. Cryoneurolysis of the auriculotemporal nerve resulted in complete resolution of otalgia for 2-3 months after first and second treatments. However, transient worsening …

Targeting Inequities: Addressing Lung Cancer Care Challenges In Africa Through Drug Access, Radiotherapy, And Surgical Innovations, Elvis Obomanu, Chidiebube Ugwu, Muluken Megiso, Tarfa Verinumbe, Colton Jones, Verna Vanderpuye, Nazik Hammad

Division of Internal Medicine Faculty Papers & Presentations

Lung cancer remains one of the leading causes of cancer-related mortality in Africa, with survival rates starkly lagging behind global benchmarks because of systemic inequities in prevention, diagnosis, and treatment access. Despite representing only 6% of global smokers, the continent faces a disproportionate burden driven by environmental and occupational carcinogens, aggressive tobacco marketing, and fragmented health care infrastructure. Key challenges include prohibitive delays in accessing targeted therapies like epidermal growth factor receptor inhibitors and immunotherapies, a dire shortage of radiotherapy infrastructure-0.12 megavoltage units per million people versus the International Atomic Energy Agency's recommended five megavoltage units per million, and a …

Long Term Evaluation Of The Safety And Efficacy Of Local Cooling Anesthesia During Intravitreal Injections: The Cool-2 Trial, Arshad M. Khanani, Samir N. Patel, Charles C. Wykoff, Gun-Ho Kim, Ajay E. Kuriyan

Wills Eye Hospital Papers

BACKGROUND/OBJECTIVE: To evaluate the safety and effectiveness of a medical device providing cooling anesthesia to the eye as local anesthesia for intravitreal (IVT) injections.

SUBJECTS/METHODS: As a multicenter, open label, dose escalation clinical trial, subjects receiving at least 3 IVT injections in the study eye were recruited to participate. All patients received subconjunctival lidocaine as their anesthesia for previous IVT injections. Subjects receiving IVT injections were assigned (non-randomized) to four groups in which the cooling device was applied to the conjunctiva at the location of the intravitreal injection: Group 1: -10˚C for 20 seconds; Group 2: -15˚C for 10 seconds; …

The Effect Of Hunger On The Likelihood Of Glucose Excursions In Adults With Overweight Or Obesity: Continuous Glucose Monitoring And Ecological Momentary Assessment Observational Study, Byunggul Lim, Phrashiah Githinji, Yue Liao, Jacob Szeszulski, Alexandra L Macmillan Uribe, Rebecca A Seguin-Fowler, Jane Anderson, Chad D Rethorst

Faculty, Staff and Students Publications

Background: Maintaining stable glucose levels is important for metabolic health. Glucose excursions (GEs), which are marked increases in glucose following food intake, have been associated with a higher risk for cardiovascular disease and metabolic dysfunction. Individuals with overweight or obesity who do not have diabetes may still show impaired glucose regulation, as reflected in increased glucose variability. Hunger, as a real-time physiological cue, may be associated with subsequent glucose changes and represents a potential target for just-in-time adaptive interventions.

Objective: This study aimed to investigate the temporal relationship between self-reported hunger and subsequent glucose dynamics, including the likelihood of GE …

Cure Sickle Cell Initiative Recommendations On Common Data Elements For Sickle Cell Disease Gene Therapy Trials, Sophie Lanzkron, Victoria H. Coleman-Cowger, Alexis A. Thompson, C. Patrick Carroll, Traci Clemons, Michael Debaun, Julie Kanter, Punam Malik, Deepa Manwani, Francis John Pierciey, Mark C. Walters, Sherita Alai

Cardeza Foundation for Hematologic Research

The Cure Sickle Cell Initiative (CureSCi), created by the National Heart, Lung, and Blood Institute, has developed data standards to increase interoperability and meta-analysis of studies specifically investigating gene therapy for sickle cell disease (SCD). The aims of the CureSCi Common Data Elements (CDE) initiative are to facilitate the development of safe, effective, and accessible gene therapies. Five working groups (WGs) comprising people living with SCD, stakeholders, clinicians, and researchers reviewed current definitions used for SCD clinical studies, including those from the American Society of Hematology, US Food and Drug Administration, PhenX catalog of consensus measures for phenotypes and exposures, …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models, Pushan Dasgupta

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Text Messaging Support For Patients Diagnosed With Impaired Glucose Tolerance During Pregnancy: Nonrandomized Pre-Post Implementation Study Assessing Impact On Postpartum Transitions Of Care, Natasha R. Kumar, Whitney Bender, Celeste Durnwald

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Patients with impaired glucose tolerance (IGT) identified during pregnancy who do not develop gestational diabetes mellitus (GDM) often do not receive additional interventions for their long-term metabolic risks.

OBJECTIVE: This nonrandomized pre-post implementation study reports the design process and initial program evaluation for Better Follow-up of Impaired Glucose Tolerance (BRIDGE), a 12-week text-based postpartum support program promoting hemoglobin A1c (HbA1c) completion and primary care provider (PCP) visit scheduling for patients diagnosed with IGT during pregnancy, assessing improvement in desired postpartum transition milestones. The 19-month program was divided into 2 arms lasting 9.5 months each, BRIDGE- (SMS text messaging support …