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Full-Text Articles in Medicine and Health Sciences

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin Jan 2025

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …


Virginia Academy Of Sleep Medicine Position Statement On School Start Times In Virginia, Sean Hesselbacher, Mariana Szklo-Coxe, Sachin Relia, Jonathan Gellman, Nicole Mcintyre Jan 2025

Virginia Academy Of Sleep Medicine Position Statement On School Start Times In Virginia, Sean Hesselbacher, Mariana Szklo-Coxe, Sachin Relia, Jonathan Gellman, Nicole Mcintyre

Eastern Virginia Medical Journal

The VASM endorses the 2017 AASM position statement that middle and high schools should begin no earlier than 8:30 a.m. The existing and updated scientific literature repeatedly identifies the detrimental impact of early high school start times, and the benefits of delaying start times, on the safety and well-being of students in Virginia. The adverse effects of early school start times on Virginia’s students have been demonstrated, with regards to academic performance, mental health, and driving risks. Data published since the AASM position paper highlight these dangers further. Importantly, recent studies also demonstrate some of the benefits that can come …


Pulmonary Pathology In Culture-Negative Sepsis: A Potential Confounder For Sepsis Treatment And Research, Brett Biebelberg Jan 2025

Pulmonary Pathology In Culture-Negative Sepsis: A Potential Confounder For Sepsis Treatment And Research, Brett Biebelberg

SKMC Student Presentations and Publications

No abstract provided.


Viscoelastic Hemostatic Assays Are Associated With Mortality And Blood Transfusion In A Multicenter Cohort, Shyam Murali, Eric Winter, Nicolas M. Chanes, Allyson M. Hynes, Madhu Subramanian, Alison A. Smith, Mark J. Seamon, Jeremy W. Cannon Jan 2025

Viscoelastic Hemostatic Assays Are Associated With Mortality And Blood Transfusion In A Multicenter Cohort, Shyam Murali, Eric Winter, Nicolas M. Chanes, Allyson M. Hynes, Madhu Subramanian, Alison A. Smith, Mark J. Seamon, Jeremy W. Cannon

School of Medicine Faculty Publications

Objectives: Trauma-induced coagulopathy (TIC) carries significant risks, including increased mortality. Traditional TIC definitions rely on laboratories that result slowly and do not highlight therapeutic targets. We hypothesized that a TIC score, based on thromboelastography (TEG) and rotational thromboelastometry (ROTEM), collectively termed viscoelastic hemostatic assays, is associated with in-hospital mortality and packed red blood cell (pRBC) transfusion. Methods: This retrospective cohort study used a database of adult patients undergoing institutional massive transfusion at seven level 1 trauma centers (2013-2018). A “TIC score” was developed, with 1 point assigned for abnormal TEG R-time ( ≥ 9 min) or ROTEM clot time ( …


Artificial Intelligence For Optical Coherence Tomography In Glaucoma, Mak B. Djulbegovic, Henry Bair, David J. Taylor Gonzalez, Hiroshi Ishikawa, Gadi Wollstein, Joel S. Schuman Jan 2025

Artificial Intelligence For Optical Coherence Tomography In Glaucoma, Mak B. Djulbegovic, Henry Bair, David J. Taylor Gonzalez, Hiroshi Ishikawa, Gadi Wollstein, Joel S. Schuman

Wills Eye Hospital Papers

PURPOSE: The integration of artificial intelligence (AI), particularly deep learning (DL), with optical coherence tomography (OCT) offers significant opportunities in the diagnosis and management of glaucoma. This article explores the application of various DL models in enhancing OCT capabilities and addresses the challenges associated with their clinical implementation.

METHODS: A review of articles utilizing DL models was conducted, including convolutional neural networks (CNNs), recurrent neural networks (RNNs), generative adversarial networks (GANs), autoencoders, and large language models (LLMs). Key developments and practical applications of these models in OCT image analysis were emphasized, particularly in the context of enhancing image quality, glaucoma …


Co-Option Of Mitochondrial Nucleic Acid-Sensing Pathways By Hsv-1 Ul12.5 For Reactivation From Latent Infection, Patryk A. Krakowiak, Matthew E. Flores, Sean R. Cuddy, Abigail L. Whitford, Sara A. Dochnal, Aleksandra Babnis, Tsuyoshi Miyake, Marco Tigano, Daniel A. Engel, Anna R. Cliffe Jan 2025

Co-Option Of Mitochondrial Nucleic Acid-Sensing Pathways By Hsv-1 Ul12.5 For Reactivation From Latent Infection, Patryk A. Krakowiak, Matthew E. Flores, Sean R. Cuddy, Abigail L. Whitford, Sara A. Dochnal, Aleksandra Babnis, Tsuyoshi Miyake, Marco Tigano, Daniel A. Engel, Anna R. Cliffe

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells. HSV-1 establishes latency in neurons and can reactivate to cause disease. We found that UL12.5 is required for HSV-1 reactivation in neurons and acts to directly promote viral lytic gene expression during initial exit from latency. Further, the direct activation of innate immune-sensing pathways triggered …


Social, Racial, And Economic Disparities Affecting Outcomes Of Hypertensive Adolescents, Kanya Singhapakdi, Amelia Haydel, Marla Johnston, Shengping Yang, Tamara Bradford, Dedrick Moulton, Thomas R. Kimball Jan 2025

Social, Racial, And Economic Disparities Affecting Outcomes Of Hypertensive Adolescents, Kanya Singhapakdi, Amelia Haydel, Marla Johnston, Shengping Yang, Tamara Bradford, Dedrick Moulton, Thomas R. Kimball

School of Medicine Faculty Publications

Essential hypertension is one of the most common conditions managed in pediatric cardiology and can result in lasting deleterious effects on the cardiovascular system. Pediatric hypertension is so prevalent in the United States that it is often referred to as a public health challenge. Social determinants of health (SDH) are the cultural, economic, educational, healthcare accessibility, and political influences in the environment in which an individual is born or lives, all of which can affect that individual's overall health. This study investigated the impact of social determinants such as rurality, food insecurity, transportation challenges, minority status, income, and race on …


Prevalence Of Autoimmune Diseases In Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network Of Health Care Organizations, Pushti Khandwala, Devashish Desai, Arthur Lau Jan 2025

Prevalence Of Autoimmune Diseases In Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network Of Health Care Organizations, Pushti Khandwala, Devashish Desai, Arthur Lau

Einstein Health Papers

OBJECTIVE: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

METHODS: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use. Multivariate Cox proportional hazard models and Kaplan Meier method were used to assess risk of developing ACs among the groups. Subgroup analysis was done to evaluate risk of ACs in patients receiving cytotoxic T-lymphocyte-associated protein 4 inhibitor (CTLA4i) versus program cell death protein 1 inhibitor (PD1i) and program death ligand 1 inhibitor (PDL1i) inhibitors and combination treatment (CT) …


Use Of Multi-Modal Non-Contrast Mri To Predict Functional Outcomes After Stroke: A Study Using Dp-Pcasl, Dti, Noddi, And Map Mri, Julia Diamandi, Christian Raimondo, Keenan Piper, Joanna Roy, Stephanie Serva, Mahdi Alizadeh, Adam Flanders, Stavropoula Tjoumakaris, Michael Gooch, Pascal Jabbour, Robert Rosenwasswer, Nikolaos Mouchtouris Jan 2025

Use Of Multi-Modal Non-Contrast Mri To Predict Functional Outcomes After Stroke: A Study Using Dp-Pcasl, Dti, Noddi, And Map Mri, Julia Diamandi, Christian Raimondo, Keenan Piper, Joanna Roy, Stephanie Serva, Mahdi Alizadeh, Adam Flanders, Stavropoula Tjoumakaris, Michael Gooch, Pascal Jabbour, Robert Rosenwasswer, Nikolaos Mouchtouris

Department of Neurosurgery Faculty Papers

PURPOSE: This study aims to assess whether water exchange rate (kw), a surrogate for blood-brain barrier (BBB) permeability, is associated with functional outcomes in patients with acute ischemic stroke (AIS).

METHODS: We studied 22 AIS patients enrolled from 1/2022 to 4/2024 who underwent multi-modal non-contrast imaging on a 3.0-Tesla scanner, including DP-pCASL, DTI, NODDI and MAP imaging. For each parametric map, the intensity and standard deviation (SD) were calculated for the infarcted region. The diffusion maps included were b0, Fractional Anisotropy (FA), Mean Diffusivity (MD), Intra-cellular Volume Fraction (ICVF), Free Water Fraction (FWF), and Orientation Dispersion Index (ODI), …


Ethnic Disparities In Hba1c And Hypoglycemia Among Youth With Type 1 Diabetes: Beyond Access To Technology, Social Deprivation And Mean Blood Glucose, J. Pemberton, Zhide Fang, Stuart Chalew, S. Uday Jan 2025

Ethnic Disparities In Hba1c And Hypoglycemia Among Youth With Type 1 Diabetes: Beyond Access To Technology, Social Deprivation And Mean Blood Glucose, J. Pemberton, Zhide Fang, Stuart Chalew, S. Uday

School of Public Health Faculty Publications

Introduction The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables. Research design and methods A retrospective analysis of participants who received structured education in continuous glucose monitoring (CGM) use was conducted at a tertiary center. HbA1c was paired with glucose metrics from 90-day CGM data. The …


A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn Jan 2025

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …


Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani Jan 2025

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …


Spatial Transcriptome Reveals Histology-Correlated Immune Signature Learnt By Deep Learning Attention Mechanism On H&E-Stained Images For Ovarian Cancer Prognosis, Chun Wai Ng, Kwong-Kwok Wong, Barrett C Lawson, Sammy Ferri-Borgogno, Samuel C Mok Jan 2025

Spatial Transcriptome Reveals Histology-Correlated Immune Signature Learnt By Deep Learning Attention Mechanism On H&E-Stained Images For Ovarian Cancer Prognosis, Chun Wai Ng, Kwong-Kwok Wong, Barrett C Lawson, Sammy Ferri-Borgogno, Samuel C Mok

Faculty, Staff and Student Publications

Background: The ability to predict the prognosis of patients with ovarian cancer can greatly improve disease management. However, the knowledge on the mechanism of the prediction is limited. We sought to deconvolute the attention feature learnt by a deep learning convolutional neural networks trained with whole-slide images (WSIs) of hematoxylin-and-eosin (H&E)-stained tumor samples using spatial transcriptomic data.

Methods: In this study, 773 WSIs of H&E-stained tumor sections from 335 patients with treatment naïve high-grade serous ovarian cancer who were included in The Cancer Genome Atlas (TCGA) Pan-Cancer study were used to train, and validate, and to test a ResNet101 CNN …


Joint Fluid Multi-Omics Improves Diagnostic Confidence During Evaluation Of Children With Presumed Septic Arthritis, Yolanda Peña-López, Naureen G Tareen, Bo Zhang, Indu Raman, Carlos A Arana, Chengsong Zhu, Yang Liu, Pratibha Selvakumar, Nicolai S C Van Oers, Simrat Morris, Lora V Hooper, Lawson A B Copley, Prithvi Raj Jan 2025

Joint Fluid Multi-Omics Improves Diagnostic Confidence During Evaluation Of Children With Presumed Septic Arthritis, Yolanda Peña-López, Naureen G Tareen, Bo Zhang, Indu Raman, Carlos A Arana, Chengsong Zhu, Yang Liu, Pratibha Selvakumar, Nicolai S C Van Oers, Simrat Morris, Lora V Hooper, Lawson A B Copley, Prithvi Raj

Faculty, Staff and Student Publications

Background: An accurate diagnosis of septic versus reactive or autoimmune arthritis remains clinically challenging. A multi-omics strategy comprising metagenomic and proteomic technologies were undertaken for children diagnosed with presumed septic arthritis to advance clinical diagnoses and care for affected individuals.

Methods: Twelve children with suspected septic arthritis were prospectively enrolled to compare standard of care tests with a rapid multi-omics approach. The multi-omics combined bacterial 16S rRNA metagenomics, single cell transcriptomics, and proteomics on knee joint fluid specimens. The diagnostic value of the multi-omics was ascertained relative to standard of care culture and PCR-negative results.

Results: Ten children with suspected …


Heartmate 3 Left Ventricular Assist Device Infection-Related Left Ventricular Pseudoaneurysm: Extirpation In The Setting Of Left Ventricular Recovery, Hari K. Rajagopal, Mark J. Zucker, J. Eduardo Rame, Louis E. Samuels, Keshava Rajagopal Jan 2025

Heartmate 3 Left Ventricular Assist Device Infection-Related Left Ventricular Pseudoaneurysm: Extirpation In The Setting Of Left Ventricular Recovery, Hari K. Rajagopal, Mark J. Zucker, J. Eduardo Rame, Louis E. Samuels, Keshava Rajagopal

Department of Surgery Faculty Papers

No abstract provided.


Perspectives On A Recently Merged Family Medicine Residency Program: A Post-Match Survey Of Ranked, Unmatched Applicants, John E. Snellings, Karo G. Ohanian, Ismail El Moudden Jan 2025

Perspectives On A Recently Merged Family Medicine Residency Program: A Post-Match Survey Of Ranked, Unmatched Applicants, John E. Snellings, Karo G. Ohanian, Ismail El Moudden

Eastern Virginia Medical Journal

Introduction: Residency program mergers are a topic of much consternation and relatively little scholarly investigation in graduate medical education. After undergoing a residency merger in July 2020, the newly formed Eastern Virginia Medical School (EVMS) Family Medicine Residency Program investigated the effects of the merger on the perspectives of the applicant pool for the subsequent 2020–2021 recruiting season. Methods: We conducted an anonymous survey of EVMS Family Medicine applicants during the 2020– 2021 recruiting season. Students who interviewed with the residency and were subsequently placed on the program’s National Residency Matching Program (NRMP) rank order list (ROL) but did not …


Provisional Stenting Of Distal Bifurcation Of Left Main Stem With Angle Equal Or More Than 90° With And Without Final Kissing Balloon: One-Year Outcomes, Ali Mahdi Mohammed Abuajmaa, Khalid Ibrahim Amber Jan 2025

Provisional Stenting Of Distal Bifurcation Of Left Main Stem With Angle Equal Or More Than 90° With And Without Final Kissing Balloon: One-Year Outcomes, Ali Mahdi Mohammed Abuajmaa, Khalid Ibrahim Amber

Journal of the Saudi Heart Association

Objective: To identify the outcomes of provisional single stent (PS) strategy without final kissing balloon (FKB) in wide angle (≥90°) distal bifurcation of the left main stem (LMS).

Methods: A pilot study of prospective interventional cohort study was conducted from January 2021 to February 2024. Patients with unprotected LMS - left anterior descending artery with LMS distal bifurcation angle ≥90° were divided into: Group I (Medina class 1,1,0 treated with PS without FKB), Group II (Medina class 1,1,1 treated with PS) which subcategorized into two subgroups; Group IIa (PS with FKB) and Group IIb (PS without FKB). One-year follow-up outcomes …


Synergistic Effects Of Extra X Chromosome On Development Of Systemic Lupus Erythematosus And Sjögren Disease In Klinefelter And Triple X Syndrome: A Retrospective Cohort Study, Anna-Kay Palmer, Irene J. Tan Jan 2025

Synergistic Effects Of Extra X Chromosome On Development Of Systemic Lupus Erythematosus And Sjögren Disease In Klinefelter And Triple X Syndrome: A Retrospective Cohort Study, Anna-Kay Palmer, Irene J. Tan

Einstein Health Papers

OBJECTIVE: Systemic lupus erythematosus (SLE) and Sjögren disease (SjD) are autoimmune diseases with significant female predominance. The prevalence of SLE is increased in Klinefelter syndrome (KS) compared with the general male population. Our study investigates the dose effects of extra X chromosomes on the development of SLE and SjD in KS and triple X syndrome compared with the general population.

METHODS: This multicenter, retrospective cohort study used TriNetX, a global federated research database. Using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes, patients with a diagnosis of SLE or SjD in the general population, as well as those …


Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba Jan 2025

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …


The Biological Intersection Between Chemotherapy-Related Cognitive Impairment And Alzheimer Disease, Matthew Torre, Camila A Zanella, Mel B Feany Jan 2025

The Biological Intersection Between Chemotherapy-Related Cognitive Impairment And Alzheimer Disease, Matthew Torre, Camila A Zanella, Mel B Feany

Duncan NRI Faculty and Staff Publications

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive deficits, termed chemotherapy-related cognitive impairment. This review discusses biologically plausible pathways underlying both disorders, with the goal of …


Inhibition Of Vascular Smooth Muscle Cell Perk/Atf4 Er Stress Signaling Protects Against Abdominal Aortic Aneurysms, Brennan Callow, Xiaobing He, Nicholas Juriga, Kevin D Mangum, Amrita Joshi, Xianying Xing, Andrea Obi, Abhijnan Chattopadhyay, Dianna M Milewicz, Mary X O'Riordan, Johann Gudjonsson, Katherine Gallagher, Frank M Davis Jan 2025

Inhibition Of Vascular Smooth Muscle Cell Perk/Atf4 Er Stress Signaling Protects Against Abdominal Aortic Aneurysms, Brennan Callow, Xiaobing He, Nicholas Juriga, Kevin D Mangum, Amrita Joshi, Xianying Xing, Andrea Obi, Abhijnan Chattopadhyay, Dianna M Milewicz, Mary X O'Riordan, Johann Gudjonsson, Katherine Gallagher, Frank M Davis

Faculty, Staff and Student Publications

Abdominal aortic aneurysms (AAA) are a life-threatening cardiovascular disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by vascular smooth muscle cell (VSMC) dysfunction and apoptosis, for which the mechanisms regulating loss of VSMCs within the aortic wall remain poorly defined. Using single-cell RNA-Seq of human AAA tissues, we identified increased activation of the endoplasmic reticulum stress response pathway, PERK/eIF2α/ATF4, in aortic VSMCs resulting in upregulation of an apoptotic cellular response. Mechanistically, we reported that aberrant TNF-α activity within the aortic wall induces VSMC ATF4 activation through the …


Cd5-Positive High-Grade B-Cell Lymphoma With Myc, Bcl2, And Bcl6 Rearrangements, Wei J Wang, Zhihong Hu Jan 2025

Cd5-Positive High-Grade B-Cell Lymphoma With Myc, Bcl2, And Bcl6 Rearrangements, Wei J Wang, Zhihong Hu

Faculty, Staff and Student Publications

No abstract provided.


Collateral Rescue, Arterial Burden: Untreated Takayasu Arteritis And Its Long-Term Complications, Ikwinder Preet Kaur, Steven Morales-Rivera, Victoria Cuello, Gurjit S. Kaeley Jan 2025

Collateral Rescue, Arterial Burden: Untreated Takayasu Arteritis And Its Long-Term Complications, Ikwinder Preet Kaur, Steven Morales-Rivera, Victoria Cuello, Gurjit S. Kaeley

School of Medicine Publications

No abstract provided.


A Deconvolution Framework That Uses Single-Cell Sequencing Plus A Small Benchmark Data Set For Accurate Analysis Of Cell Type Ratios In Complex Tissue Samples, Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A Owen, Ivana K Kim, Ana Aparicio, Sanghoon Lee, Anil K Sood, Scott Kopetz, John Paul Shen, John N Weinstein, Margaret M Deangelis, Rui Chen, Wenyi Wang Jan 2025

A Deconvolution Framework That Uses Single-Cell Sequencing Plus A Small Benchmark Data Set For Accurate Analysis Of Cell Type Ratios In Complex Tissue Samples, Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A Owen, Ivana K Kim, Ana Aparicio, Sanghoon Lee, Anil K Sood, Scott Kopetz, John Paul Shen, John N Weinstein, Margaret M Deangelis, Rui Chen, Wenyi Wang

Faculty, Staff and Student Publications

Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using this well-matched, that is, benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using two benchmark data sets of healthy retinas and …


Multicenter Prospective Pilot Study Identifying Thrombomodulin As A Potential Biomarker For Neurocognitive Outcomes In Immune Thrombotic Thrombocytopenic Purpura, Aaron B Boothby, Michael D Evans, Shangbin Yang, Senthil Sukumar, James G Scott, Deirdra R Terrell, Spero Cataland, Marshall Mazepa Jan 2025

Multicenter Prospective Pilot Study Identifying Thrombomodulin As A Potential Biomarker For Neurocognitive Outcomes In Immune Thrombotic Thrombocytopenic Purpura, Aaron B Boothby, Michael D Evans, Shangbin Yang, Senthil Sukumar, James G Scott, Deirdra R Terrell, Spero Cataland, Marshall Mazepa

Faculty, Staff and Students Publications

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers.

Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month …


Advances In Multiple Sclerosis, Victor M Rivera Jan 2025

Advances In Multiple Sclerosis, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...].


Dna Methylation Profiling At Base-Pair Resolution Reveals Unique Epigenetic Features Of Early-Onset Colorectal Cancer In Underrepresented Populations, Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen Jan 2025

Dna Methylation Profiling At Base-Pair Resolution Reveals Unique Epigenetic Features Of Early-Onset Colorectal Cancer In Underrepresented Populations, Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

RESULTS: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top …


Stratification System With Dual Human Endogenous Retroviruses For Predicting Immunotherapy Efficacy In Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf Jan 2025

Stratification System With Dual Human Endogenous Retroviruses For Predicting Immunotherapy Efficacy In Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial. ERV expression was quantified using the ERVmap algorithm …


Optimized Methods To Quantify Tumor Treating Fields (Ttfields)-Induced Permeabilization Of Glioblastoma Cell Membranes, Melisa Martinez-Paniagua, Sabbir Khan, Nikita W Henning, Sri Vaishnavi Konagalla, Chirag B Patel Jan 2025

Optimized Methods To Quantify Tumor Treating Fields (Ttfields)-Induced Permeabilization Of Glioblastoma Cell Membranes, Melisa Martinez-Paniagua, Sabbir Khan, Nikita W Henning, Sri Vaishnavi Konagalla, Chirag B Patel

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a lethal primary brain cancer with a 5.6% five-year survival rate. Tumor treating fields (TTFields) are alternating low-intensity electric fields that have demonstrated a GBM patient survival benefit. We previously reported that 0.5-24 h of TTFields exposure resulted in an increased uptake of FITC-dextran fluorescent probes (4-20 kDa) in human GBM cells. However, this approach, in which a fluorescence plate-based detector is used to evaluate cells attached to glass coverslips, cannot distinguish FITC-dextran uptake in live vs. dead cells. The goal of the study was to report the optimization and validation of two independent methods to quantify …


Case Report On Endocrine Induced Paralysis - " Unraveling The Impact Of Thyrotoxicosis On Potassium Homeostasis.", Srujith Pullipudi, Basava Chethan, Srinath K. M, Savitha Vijayakumar, Meghna B.S. Jan 2025

Case Report On Endocrine Induced Paralysis - " Unraveling The Impact Of Thyrotoxicosis On Potassium Homeostasis.", Srujith Pullipudi, Basava Chethan, Srinath K. M, Savitha Vijayakumar, Meghna B.S.

Digital Journal of Clinical Medicine

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, marked by episodes of muscle weakness and hypokalaemia. Although it predominantly affects young Asian men, it can also occur in females and individuals from non-Asian ethnic groups. TPP is a treatable form of hypokalaemic periodic paralysis and can often be the first indication of thyrotoxicosis. Triggers such as a high-carbohydrate diet, strenuous exercise, emotional stress, and steroid use can provoke TPP attacks. During an acute episode, the key diagnostic indicators are hypokalaemia along with elevated levels of thyroxine (T4) and triiodothyronine (T3). Treatment consists of two phases: promptly correcting hypokalaemia …