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Prenatal Alcohol Exposure Inhibits Transient Expression Of Autophagy And Synaptic Proteins In Developing Brain, Monica Hampe, Nune Darbinian, Nana Merabova, Armine Darbinyan, Jamal Hamze, Uday Bharai, Yuri Persidsky, Mary F Morrison, Shohreh Amini, Laura Goetzl, Michael E Selzer Jan 2025

Prenatal Alcohol Exposure Inhibits Transient Expression Of Autophagy And Synaptic Proteins In Developing Brain, Monica Hampe, Nune Darbinian, Nana Merabova, Armine Darbinyan, Jamal Hamze, Uday Bharai, Yuri Persidsky, Mary F Morrison, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: Neuronal apoptosis and consequent inhibition of autophagy, with loss of synaptic connections are central events in the genesis of fetal alcohol spectrum disorders (FASD). However, studies of molecular mechanisms of autophagy in human fetal brain are limited. Recently, prenatal exposure to EtOH was associated with reduced miRNA-9 levels in fetal brain-derived exosomes (FB- Es) isolated from maternal plasma, which correlated with small eyes, an anatomical hallmark of fetal alcohol syndrome (FAS). Since miR-9 targets several genes that regulate synaptic plasticity, EtOH-induced inhibition of miR-9 could potentially result in dysregulation of genes involved in synaptogenesis/plasticity.

Methods: Rats were fed a …


The Short And Sweet On Sodium-Glucose Cotransporter Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists In Heart Failure, Jose L. Batista, Tracy Makuvire, Jonathan D. Davis, Salvatore Carbone Jan 2025

The Short And Sweet On Sodium-Glucose Cotransporter Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists In Heart Failure, Jose L. Batista, Tracy Makuvire, Jonathan D. Davis, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Heart failure (HF) affects 6 million people in the US, and type 2 diabetes (T2D) is a significant risk factor for HF. Since 2008, regulatory agencies have required cardiovascular safety trials for new T2D therapies, and these have consistently demonstrated the cardiovascular benefits of glucose-lowering drugs. Sodium-glucose cotransporter inhibitors (SGLTi) and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs)/glucose-dependent insulinotropic polypeptide (GIP) reduce major adverse cardiovascular events and deaths, regardless of diabetes status, and improve cardiorespiratory fitness. SGLTis, such as dapagliflozin and empagliflozin, benefit patients with reduced and preserved ejection fraction, significantly reducing HF hospitalizations and cardiovascular deaths. The DAPA-HF and EMPEROR-Reduced …


Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran Jan 2025

Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

Background: Transcranial direct current stimulation is a non-invasive neuromodulation technique with emerging therapeutic potential in neurodevelopmental conditions. While childhood-onset stroke survivors frequently experience long-term motor impairment, there are very few studies examining the safety and feasibility of transcranial direct current stimulation in this population.

Objective: To evaluate the safety, feasibility, and tolerability of bihemispheric transcranial direct current stimulation paired with occupational therapy in children and adolescents with chronic hemiparesis following childhood-onset arterial ischemic stroke or intracranial hemorrhage.

Methods: In this single-arm, open-label pilot study, five participants aged 6-19 years of age received five daily sessions of transcranial direct current stimulation …


Racial Differences In Systemic Immune Parameters In Individuals With Lung Cancer, Mitchell S Von Itzstein, Jialiang Liu, Hong Mu-Mosley, Farjana Fattah, Jason Y Park, Jeffrey A Sorelle, J David Farrar, Mary E Gwin, David Hsiehchen, Yvonne Gloria-Mccutchen, Edward K Wakeland, Suzanne Cole, Sheena Bhalla, Radhika Kainthla, Igor Puzanov, Benjamin Switzer, Gregory A Daniels, Yousef Zakharia, Montaser Shaheen, Jianjun Zhang, Yang Xie, David E Gerber Jan 2025

Racial Differences In Systemic Immune Parameters In Individuals With Lung Cancer, Mitchell S Von Itzstein, Jialiang Liu, Hong Mu-Mosley, Farjana Fattah, Jason Y Park, Jeffrey A Sorelle, J David Farrar, Mary E Gwin, David Hsiehchen, Yvonne Gloria-Mccutchen, Edward K Wakeland, Suzanne Cole, Sheena Bhalla, Radhika Kainthla, Igor Puzanov, Benjamin Switzer, Gregory A Daniels, Yousef Zakharia, Montaser Shaheen, Jianjun Zhang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Introduction: Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer.

Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pretreatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons.

Results: A …


Burkitt's Lymphoma Presenting As Multiple Nerve Sheath Tumors Of The Cauda Equina., Jason Milton, Punit Pandya, Sergio Ulloa, Vijay Kudithipudi, Shakir Sarwar, Victor Awuor Jan 2025

Burkitt's Lymphoma Presenting As Multiple Nerve Sheath Tumors Of The Cauda Equina., Jason Milton, Punit Pandya, Sergio Ulloa, Vijay Kudithipudi, Shakir Sarwar, Victor Awuor

Oncology Articles

BACKGROUND: Primary central nervous system lymphomas comprise 0.8% of all lymphomas. Burkitt's lymphoma is a B-cell lymphoma with highly aggressive features that rapidly progress and have early hematogenous spread. Sporadic Burkitt's lymphoma accounts for 1-2% of adult lymphomas worldwide. Extranodal sites are involved in approximately 40% of cases of B-cell lymphomas. Central nervous system disease is found in < 15% of sporadic cases. Less than 5% of cases of all non-Hodgkin's lymphomas present with radiculopathy, with the thoracic spinal region being most commonly affected.

CASE DESCRIPTION: In this report, we discuss the case of a patient with extranodal Burkitt's lymphoma within the nerve roots of the cauda equina who underwent surgical intervention due to the presence of lumbar radiculopathy and weakness. This patient also exhibited hematogenous …


Prophylactic Use Of Lipid Emulsion Therapy After Inadvertent Administration Of 0.5% Ropivacaine For A Bier Block: A Case Report., Alexander Luong, Sirimas Lau, Elizabeth Johnson-Gray, Rayyan Bhutta, Austin Shaffer, Mitchell Hughes, Andrew Gable, Matthias Franzen Jan 2025

Prophylactic Use Of Lipid Emulsion Therapy After Inadvertent Administration Of 0.5% Ropivacaine For A Bier Block: A Case Report., Alexander Luong, Sirimas Lau, Elizabeth Johnson-Gray, Rayyan Bhutta, Austin Shaffer, Mitchell Hughes, Andrew Gable, Matthias Franzen

Surgery Articles

The Bier block for intravenous regional anesthesia is generally well tolerated, and few complications have been reported. It provides a bloodless surgical field and adequate analgesia when performed correctly. A diluted short-acting local anesthetic such as 0.5% lidocaine is typically used. Our case is a 41-year-old female who presented for endoscopic carpal tunnel release of her right wrist. An accidental injection of 30 mL of 0.5% ropivacaine was given instead of the normal 30 mL of 0.5% lidocaine, with a total tourniquet time of 46 min. Although the maximum safe dose of local anesthetic was not exceeded, lipid emulsion was …


A Primer On Anatomy, Biophysics, Pathology, Imaging And Treatment Of The Intervertebral Disc And The Anterior Spinal Column: The Discogenic, Intervertebral, Spinal Column (Disc) Aspn Workgroup., Jay S Grider, Timothy R Deer, Douglas P Beall, Melissa Z Murphy, Jacob W Fleming, Steven M Falowski, Christopher J Mallard, Hamzah A Ramawad, Rosa Amelia Garcia, Usman Latif, Chau M Vu, Anne Christopher, Michael E Harned, Raj G Patel, Anuj J Shah, Iden M Cowan, Kristin Jarzombek, Jordan L Tate, Nasir Khatri, Mateusz J Graca, Marcin K Karcz, Timothy T Davis, Kaku Barkoh, Olivier Clerk-Lamalice, Brian Durkin, Mark N Malinowski, Dagmar K Gross, Thomas Hedman, Matthew Green, Michael J Dorsi, Kasra Amirdelfan, Dawood Sayed Jan 2025

A Primer On Anatomy, Biophysics, Pathology, Imaging And Treatment Of The Intervertebral Disc And The Anterior Spinal Column: The Discogenic, Intervertebral, Spinal Column (Disc) Aspn Workgroup., Jay S Grider, Timothy R Deer, Douglas P Beall, Melissa Z Murphy, Jacob W Fleming, Steven M Falowski, Christopher J Mallard, Hamzah A Ramawad, Rosa Amelia Garcia, Usman Latif, Chau M Vu, Anne Christopher, Michael E Harned, Raj G Patel, Anuj J Shah, Iden M Cowan, Kristin Jarzombek, Jordan L Tate, Nasir Khatri, Mateusz J Graca, Marcin K Karcz, Timothy T Davis, Kaku Barkoh, Olivier Clerk-Lamalice, Brian Durkin, Mark N Malinowski, Dagmar K Gross, Thomas Hedman, Matthew Green, Michael J Dorsi, Kasra Amirdelfan, Dawood Sayed

Surgery Articles

OBJECTIVE: As therapeutic options are rapidly expanding to treat pain of discogenic and vertebrogenic origin, it is important for the clinician to have an evidence-based understanding of the latest information regarding the normal and pathological anatomy of the intervertebral disc as well as imaging characteristics and treatment strategies. The American Society of Pain and Neuroscience (ASPN) commissioned the DISC project to inform and update the interventional spine community about anterior column pain syndromes.

METHODS: Using established literature review methods a clinical oversight group was convened to create an outline covering topics that will be key to meeting the objectives delineated …


An Evidence-Based Consensus For The Use Of Neurostimulation For The Treatment Of Non-Surgical Low Back Pain: The Neuron Group., Timothy Ray Deer, Jason E Pope, Erika A Petersen, Rany T Abdallah, Kasra Amirdelfan, Nomen Azeem, Vishal Bansal, Kaku Barkoh, Kenneth B Chapman, Daniel R Denis, Michael J Dorsi, Alexander Escobar, Steven Michael Falowski, Rosa Amelia Garcia, Jonathan M Hagedorn, Robert D Heros, Whitney S James, Hemant Kalia, Todd Lansford, Mark N Malinowski, Suzanne Marie Manzi, Pankaj Mehta, Robert Z Moghim, Gregory Anthony Moore, Soriaya Lizette Motivala, Yeshvant A Navalgund, Raj G Patel, Julie G Pilitsis, Michael E Schatman, Philip Michael Shumsky, Natalie Holmes Strand, Nestor D Tomycz, James J Yue, Dawood Sayed Jan 2025

An Evidence-Based Consensus For The Use Of Neurostimulation For The Treatment Of Non-Surgical Low Back Pain: The Neuron Group., Timothy Ray Deer, Jason E Pope, Erika A Petersen, Rany T Abdallah, Kasra Amirdelfan, Nomen Azeem, Vishal Bansal, Kaku Barkoh, Kenneth B Chapman, Daniel R Denis, Michael J Dorsi, Alexander Escobar, Steven Michael Falowski, Rosa Amelia Garcia, Jonathan M Hagedorn, Robert D Heros, Whitney S James, Hemant Kalia, Todd Lansford, Mark N Malinowski, Suzanne Marie Manzi, Pankaj Mehta, Robert Z Moghim, Gregory Anthony Moore, Soriaya Lizette Motivala, Yeshvant A Navalgund, Raj G Patel, Julie G Pilitsis, Michael E Schatman, Philip Michael Shumsky, Natalie Holmes Strand, Nestor D Tomycz, James J Yue, Dawood Sayed

Neuroscience Articles

INTRODUCTION: The use of electrical neuromodulation has often been limited to those with previous back surgery, peripheral neuropathy, and complex regional pain syndrome. Many patients with severe intractable low back pain were thought to be candidates for spinal cord stimulation (SCS), dorsal root ganglion stimulation, or peripheral nerve stimulation but did not meet the criteria. Recently, additional high-level data has supported the use of SCS in non-surgical low back pain (NSLBP), and United States Food and Drug Administration approval has been granted. The American Society of Pain and Neuroscience (ASPN) executive committee realized an unmet need to develop criteria for …


Associations Of Vegetable And Potato Intakes With Markers Of Type 2 Diabetes Risk In The Ausdiab Cohort, Pratik Pokharel, Lauren C. Blekkenhorst, Catherine P. Bondonno, Kevin Murray, Simone Radavelli-Bagatini, Dianna J. Magliano, Robin M. Daly, Jonathan E. Shaw, Joshua Lewis, Jonathan M. Hodgson, Nicola P. Bondonno Jan 2025

Associations Of Vegetable And Potato Intakes With Markers Of Type 2 Diabetes Risk In The Ausdiab Cohort, Pratik Pokharel, Lauren C. Blekkenhorst, Catherine P. Bondonno, Kevin Murray, Simone Radavelli-Bagatini, Dianna J. Magliano, Robin M. Daly, Jonathan E. Shaw, Joshua Lewis, Jonathan M. Hodgson, Nicola P. Bondonno

Research outputs 2022 to 2026

Context: The associations of vegetable and potato intakes with type 2 diabetes (T2D) appear to be nuanced, depending on vegetable types and preparation method, respectively.

Objective: We investigated the associations of total vegetable, vegetable subgroup, and potato intakes with (1) markers of T2D at baseline and (2) incident T2D cumulative over a 12-year follow-up period in Australian adults.

Methods: Using data from the Australian Diabetes, Obesity and Lifestyle Study, intakes of vegetables and potatoes were assessed via a food frequency questionnaire at baseline. Associations between vegetable intake and (1) fasting plasma glucose (FPG), 2-hour postload plasma glucose (PLG), updated homeostasis …


Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle Jan 2025

Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Background: Posttraumatic stress disorder (PTSD) symptoms are common in people with cocaine use disorder (CUD), and even sub-threshold PSTD symptoms result in worse treatment outcomes. Difficulties with reward functioning may drive this comorbidity. Impairments in reward functioning are prominent in both PTSD and CUD and contribute to development of substance use problems after trauma. There are three distinct reward processes that may be involved in the PTSD/CUD overlap: consummatory reward (ability to experience pleasure), motivational reward (willingness to exert effort for rewards), and reward learning (adapting behavior based on reward history). Here we test whether impairments in these reward functions …


Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt Jan 2025

Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt

Faculty, Staff and Student Publications

Background: Magnetic resonance (MR) guided radiation therapy combines high-resolution image capabilities of MRI with the precise targeting of radiation therapy. However, MRI does not provide the essential electron density information for accurate dose calculation, which limit the application of MRI. In this presented work, we evaluated the potential for Deep Learning (DL) based synthetic CT (sCT) generation using 3D MRI setup scans acquired during real-time adaptive MRI-guided radiation therapy.

Methods: We trained and evaluated a Cycle-consistent Generative Adversarial Network (Cycle-GAN) using paired MRI and deformably registered CT scan slices (dCT) in the context of real-time adaptive MRI-guided radiation therapy. Synthetic …


Comb-Boin12: A Utility-Based Bayesian Optimal Interval Design For Dose Optimization In Cancer Drug-Combination Trials, Mengyi Lu, Jingyi Zhang, Ying Yuan, Ruitao Lin Jan 2025

Comb-Boin12: A Utility-Based Bayesian Optimal Interval Design For Dose Optimization In Cancer Drug-Combination Trials, Mengyi Lu, Jingyi Zhang, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Drug combinations are increasingly utilized in cancer treatment to enhance drug effectiveness through synergistic therapeutic effects. However, determining the optimal biological dose combination (OBDC) in small-scale drug combination trials presents challenges due to the increased complexity of the dose space. To effectively optimize the dose combination of combined drugs, we propose a model-assisted design by extending the single-agent Bayesian optimal interval phase I/II (BOIN12) design. Our approach incorporates a utility function to balance the trade-off between risk and benefit and directly models the utility of each dose by constructing a quasi-beta-binomial model. A key advantage of our design is the …


Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou Jan 2025

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …


Accumulated Seizure Burden Predicts Neurodevelopmental Outcome At 36 Months Of Age In Patients With Tuberous Sclerosis Complex, S Katie Z Ihnen, Samuel Alperin, Jamie K Capal, Alexander L Cohen, Jurriaan M Peters, E Martina Bebin, Hope A Northrup, Mustafa Sahin, Darcy A Krueger Jan 2025

Accumulated Seizure Burden Predicts Neurodevelopmental Outcome At 36 Months Of Age In Patients With Tuberous Sclerosis Complex, S Katie Z Ihnen, Samuel Alperin, Jamie K Capal, Alexander L Cohen, Jurriaan M Peters, E Martina Bebin, Hope A Northrup, Mustafa Sahin, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear.

Methods: Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of …


Development Of Microcystoid Macular Degeneration In The Retina Of Nonhuman Primates: Time-Course And Associated Pathologies, Thomas C M Lavery, Carol A Rasmussen, Alexander W Katz, Charlene B Y Kim, James N Ver Hoeve, Paul E Miller, Peter J Sonnentag, Brian J Christian, Christopher J Murphy, David R Piwnica-Worms, Seth T Gammon, Xudong Qiu, Paul L Kaufman, T Michael Nork Jan 2025

Development Of Microcystoid Macular Degeneration In The Retina Of Nonhuman Primates: Time-Course And Associated Pathologies, Thomas C M Lavery, Carol A Rasmussen, Alexander W Katz, Charlene B Y Kim, James N Ver Hoeve, Paul E Miller, Peter J Sonnentag, Brian J Christian, Christopher J Murphy, David R Piwnica-Worms, Seth T Gammon, Xudong Qiu, Paul L Kaufman, T Michael Nork

Faculty, Staff and Student Publications

Purpose: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.

Methods: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous …


Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu Jan 2025

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin


Correction: Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran Jan 2025

Correction: Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

[This corrects the article DOI: 10.3389/fnhum.2025.1629499.].


Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior Jan 2025

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior

Faculty, Staff and Student Publications

No abstract provided.


Mechanisms Of How Sarcopenia Affects Functional Outcomes In Acute Ischaemic Stroke, Dong-Seok Gwak, Jinyong Chung, Dawid Schellingerhout, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Dong-Eog Kim Jan 2025

Mechanisms Of How Sarcopenia Affects Functional Outcomes In Acute Ischaemic Stroke, Dong-Seok Gwak, Jinyong Chung, Dawid Schellingerhout, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Dong-Eog Kim

Faculty, Staff and Student Publications

Sarcopenia, a common geriatric condition characterized by the loss of skeletal muscle mass and function, can negatively affect functional outcomes in acute ischaemic stroke; however, the underlying mechanisms remain unclear. We hypothesized that sarcopenia affects post-stroke outcomes, mediated through its impact on dysphagia, early neurological deterioration, or post-stroke recovery, particularly in patients with motor deficits. To explore this hypothesis, we included 600 consecutive elderly (≥65 years) patients with acute (< 1 week) ischaemic stroke and assessed: (i) the relationships sarcopenia has with dysphagia, early neurological deterioration and various phases of recovery after stroke (in-hospital, post-discharge [up to 3 months], and chronic [3 months to 1 year]) and (ii) whether either presenting symptoms or lesion locations modify the impact of sarcopenia on stroke outcomes. Temporal muscle thickness, a marker of sarcopenia, was measured by brain magnetic resonance imaging and dichotomized into low versus high temporal muscle thickness at the 25th percentile cut-off point. Logistic regression analysis, mediation analysis and statistical brain mapping were conducted. Mean age was 75.3 ± 6.1 years and 303 (50.5%) were male. Low temporal muscle thickness (< 5.1 mm) was independently associated with dysphagia (adjusted odds ratio 1.89 [95% confidence interval 1.06–3.37], P = 0.03), early neurological deterioration (adjusted odds ratio 2.75 [95% confidence interval 1.61–4.71], P < 0.001) and post-discharge recovery (adjusted odds ratio 0.56 [95% confidence interval 0.34–0.94], P = 0.03) but not with in-hospital or chronic recovery. In addition, dysphagia, early neurological …


High Neuraxial Blockade In A Parturient After Epidural Placement: A Quality Improvement Simulation., Samir Patel, Noah D Le, John Carter, Nick Melott, Andrew Kalnow, Camille D Hawkins, Alexander Luong, Matthias Franzen Jan 2025

High Neuraxial Blockade In A Parturient After Epidural Placement: A Quality Improvement Simulation., Samir Patel, Noah D Le, John Carter, Nick Melott, Andrew Kalnow, Camille D Hawkins, Alexander Luong, Matthias Franzen

Medical Education Articles

Background Epidural anesthesia is a commonly used procedure in obstetrics for managing labor pain, with a potential complication of high neuraxial blockade. Proficiency in performing epidural or spinal anesthesia and promptly recognizing and managing high neuraxial blockade are critical components of anesthesiology residency training. Methods A simulated case was designed involving a 21-year-old female in labor receiving epidural anesthesia. After the administration of local anesthetic, she develops symptoms of nausea, hypotension, and respiratory distress, progressing to high neuraxial blockade. The simulation environment included a labor and delivery suite setup, an epidural cart, airway supplies, a Laerdal SimMan 3G PLUS mannequin …


Cochlear Implantation With Sporadic Inner Ear Schwannomas: Outcomes In 106 Patients From An International Multi-Institutional Study, John P. Marinelli, Torsten Rahne, James R. Dornhoffer, Christine M. Lohse, Justin Cottrell, J. Thomas Roland, Nicholas J. Thompson, Kevin D. Brown, Jacob C. Lucas, Seilesh C. Babu, Nathan R. Lindquist, Elizabeth L. Perkins, Donald Tan, John I. Lane, Jacob B. Hunter, Erin Harvey, Nicholas L. Deep, Samantha Y. Cerasiello, Matthew L. Kircher, Mana Espahbodi, Evan L. Tooker, Niels Cramer West, Per Caye-Thomasen, Matthew L. Carlson, Stefan K. Plontke Jan 2025

Cochlear Implantation With Sporadic Inner Ear Schwannomas: Outcomes In 106 Patients From An International Multi-Institutional Study, John P. Marinelli, Torsten Rahne, James R. Dornhoffer, Christine M. Lohse, Justin Cottrell, J. Thomas Roland, Nicholas J. Thompson, Kevin D. Brown, Jacob C. Lucas, Seilesh C. Babu, Nathan R. Lindquist, Elizabeth L. Perkins, Donald Tan, John I. Lane, Jacob B. Hunter, Erin Harvey, Nicholas L. Deep, Samantha Y. Cerasiello, Matthew L. Kircher, Mana Espahbodi, Evan L. Tooker, Niels Cramer West, Per Caye-Thomasen, Matthew L. Carlson, Stefan K. Plontke

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To evaluate cochlear implant speech perception among patients with sporadic inner ear schwannoma who underwent ipsilateral implantation.

STUDY DESIGN: Retrospective multi-institutional cohort study.

SETTING: Eleven tertiary academic medical centers across Germany, Denmark, and the United States.

PATIENTS: One hundred six patients with sporadic inner ear schwannoma who received an ipsilateral cochlear implant from 2011 to 2022.

INTERVENTIONS: Ipsilateral cochlear implantation with observation, stereotactic radiosurgery, or microsurgery for tumor management.

MAIN OUTCOME MEASURES: Monosyllabic speech perception testing scores and rates of open-set speech perception.

RESULTS: Among 106 patients studied, 101 (95%) achieved open-set speech perception with a median of 24 …


Longitudinal Genomic Profiling Of Chemotherapy-Related Chip Variants In Patients With Ovarian Cancer, Sara Corvigno, Jun Yao, Amma Asare, Li Zhao, Joseph Celestino, Richard A Hajek, Ency A Arboleda Goette, Ridge T Rogers, Raymond N Montoya, Ping Song, Qingxiu C Zhang, Xingzhi Song, Mohammad M Mohammad, Kenna R Shaw, Jianhua Zhang, Karen H Lu, Amir A Jazaeri, Shannon N Westin, Anil K Sood, Sanghoon Lee Jan 2025

Longitudinal Genomic Profiling Of Chemotherapy-Related Chip Variants In Patients With Ovarian Cancer, Sara Corvigno, Jun Yao, Amma Asare, Li Zhao, Joseph Celestino, Richard A Hajek, Ency A Arboleda Goette, Ridge T Rogers, Raymond N Montoya, Ping Song, Qingxiu C Zhang, Xingzhi Song, Mohammad M Mohammad, Kenna R Shaw, Jianhua Zhang, Karen H Lu, Amir A Jazaeri, Shannon N Westin, Anil K Sood, Sanghoon Lee

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis (CH) is characterized by the presence of hematopoietic stem cells (HSCs) with the potential of clonally expanding and giving rise to hematological malignancies. Clonal hematopoiesis of indeterminate potential (CHIP) is the outgrowth of a single HSC clone with an acquired somatic mutation in the absence of hematological abnormalities. CHIP variants occur with a variant allele frequency (VAF) of at least 2% in peripheral blood. This definition does not account for less frequent mutations that give rise to hematopoietic clones. Previous studies indicate an association between CH and secondary hematologic malignancies in cancer patients who receive chemotherapy.

Methods: …


A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu Jan 2025

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …


Recovery Of Verbal Working Memory Depends On Left Hemisphere White Matter Tracts, Randi C Martin, Junhua Ding, Ali I Alwani, Steve H Fung, Tatiana T Schnur Jan 2025

Recovery Of Verbal Working Memory Depends On Left Hemisphere White Matter Tracts, Randi C Martin, Junhua Ding, Ali I Alwani, Steve H Fung, Tatiana T Schnur

Faculty, Staff and Student Publications

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere. Many investigations of recovery focus on changes in gray matter regions, whereas relatively few examine white matter tracts and none address the role of these tracts in the recovery of verbal working memory. The present study addressed these gaps, examining the role of left versus right hemisphere tracts in the longitudinal recovery of phonological and semantic working memory. For 24 individuals with left hemisphere stroke, we assessed working memory performance within 1 …


Practical Application Of Multivendor Mri-Based R2* Mapping For Liver Iron Quantification At 15 T And 30 T, Gregory Simchick, Ruiyang Zhao, Qing Yuan, Mounes Aliyari Ghasabeh, Stefan Ruschke, Dimitrios C Karampinos, David T Harris, Raphael Do Vale Souza, Ryan J Mattison, Michael R Jeng, Ivan Pedrosa, Ihab R Kamel, Shreyas Vasanawala, Takeshi Yokoo, Scott B Reeder, Diego Hernando Jan 2025

Practical Application Of Multivendor Mri-Based R2* Mapping For Liver Iron Quantification At 15 T And 30 T, Gregory Simchick, Ruiyang Zhao, Qing Yuan, Mounes Aliyari Ghasabeh, Stefan Ruschke, Dimitrios C Karampinos, David T Harris, Raphael Do Vale Souza, Ryan J Mattison, Michael R Jeng, Ivan Pedrosa, Ihab R Kamel, Shreyas Vasanawala, Takeshi Yokoo, Scott B Reeder, Diego Hernando

Faculty, Staff and Student Publications

Background: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear.

Purpose: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions.

Study type: Prospective.

Subjects: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers.

Field strength/sequence: Standardized multiecho spoiled gradient echo sequence at 1.5 T and …


Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu Jan 2025

Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain …


Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov Jan 2025

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose

To combine deep learning and biology-based modeling to predict the response of locally advanced, triple-negative breast cancer before initiating neoadjuvant chemotherapy (NAC).

Materials and Methods

In this retrospective study, a biology-based mathematical model of tumor response to NAC was constructed and calibrated on a patient-specific basis using imaging data from patients enrolled in the MD Anderson A Robust TNBC Evaluation FraMework to Improve Survival trial (ARTEMIS; ClinicalTrials.gov registration no. NCT02276443) between April 2018 and May 2021. To relate the calibrated parameters in the biology-based model and pretreatment MRI data, a convolutional neural network (CNN) was employed. The CNN …


Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri Jan 2025

Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Methods: We performed a retrospective chart review of 476 patients treated with ICIs for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to the results of BAL cell percentage, confirmed the diagnosis of ICIP or other …


The Tripod-Llm Reporting Guideline For Studies Using Large Language Models, Jack Gallifant, Majid Afshar, Saleem Ameen, Yindalon Aphinyanaphongs, Shan Chen, Giovanni Cacciamani, Dina Demner-Fushman, Dmitriy Dligach, Roxana Daneshjou, Chrystinne Fernandes, Lasse Hyldig Hansen, Adam Landman, Lisa Lehmann, Liam G Mccoy, Timothy Miller, Amy Moreno, Nikolaj Munch, David Restrepo, Guergana Savova, Renato Umeton, Judy Wawira Gichoya, Gary S Collins, Karel G M Moons, Leo A Celi, Danielle S Bitterman Jan 2025

The Tripod-Llm Reporting Guideline For Studies Using Large Language Models, Jack Gallifant, Majid Afshar, Saleem Ameen, Yindalon Aphinyanaphongs, Shan Chen, Giovanni Cacciamani, Dina Demner-Fushman, Dmitriy Dligach, Roxana Daneshjou, Chrystinne Fernandes, Lasse Hyldig Hansen, Adam Landman, Lisa Lehmann, Liam G Mccoy, Timothy Miller, Amy Moreno, Nikolaj Munch, David Restrepo, Guergana Savova, Renato Umeton, Judy Wawira Gichoya, Gary S Collins, Karel G M Moons, Leo A Celi, Danielle S Bitterman

Faculty, Staff and Student Publications

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion. The guidelines introduce a modular format accommodating various LLM research designs and tasks, with 14 main items and 32 subitems applicable across all categories. Developed through an expedited Delphi process and expert consensus, TRIPOD-LLM emphasizes …


Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos Jan 2025

Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos

Faculty, Staff and Student Publications

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson …