Medical Specialties Commons^™

A Lamprey Neural Cell Type Atlas Illuminates The Origins Of The Vertebrate Brain, Francesco Lamanna, Francisca Hervas-Sotomayor, A. Phillip Oel, David Jandzik, Daniel Sobrido-Cameán, Gabriel N. Santos-Durán, Megan L. Martik, Jan Stundl, Stephen A. Green, Thoomke Brüning, Katharina Mößinger, Julia Schmidt, Celine Schneider, Mari Sepp, Florent Murat, Jeramiah J. Smith, Marianne E. Bronner, María Celina Rodicio, Antón Barreiro-Iglesias, Daniel M. Medeiros, Detlev Arendt, Henrik Kaessmann

Markey Cancer Center Faculty Publications

The vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey—a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits—based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of cell types, tissue structures and gene expression programs of the ancestral vertebrate brain. However, our analyses also revealed …

Bacteroides Fragilis In The Gut Microbiomes Of Alzheimer’S Disease Activates Microglia And Triggers Pathogenesis In Neuronal C/Ebpβ Transgenic Mice, Yiyuan Xia, Yifan Xiao, Zi-Hao Wang, Ashfaqul M. Alam, John P. Haran, Beth A. Mccormick, Xiji Shu, Xiaochuan Wang, Keqiang Ye

Markey Cancer Center Faculty Publications

Gut dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPβ transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPβ transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPβ/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors’ fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing …

New Insights On The Differential Interaction Of Sulfiredoxin With Members Of The Peroxiredoxin Family Revealed By Protein-Protein Docking And Experimental Studies, Murli Mishra, Hong Jiang, Qiou Wei

Markey Cancer Center Faculty Publications

Sulfiredoxin (Srx) is the enzyme that restores the peroxidase activity of peroxiredoxins (Prxs) through catalyzing the reduction of hyperoxidized Prxs back to their active forms. This process involves protein-protein interaction in an enzyme-substrate binding manner. The integrity of the Srx-Prx axis contributes to the pathogenesis of various oxidative stress related human disorders including cancer, inflammation, cardiovascular and neurological diseases. The purpose of this study is to understand the structural and molecular biology of the Srx-Prx interaction, which may be of significance for prediction of target site for the novel drug-discovery. Homology modeling and protein-protein docking approaches were applied to examine …

Syne1 Mutation Is Associated With Increased Tumor Mutation Burden And Immune Cell Infiltration In Ovarian Cancer, Laura M. Harbin, Nan Lin, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer …

Interferon-Stimulated Gene Tdrd7 Interacts With Ampk And Inhibits Its Activation To Suppress Viral Replication And Pathogenesis, Sukanya Chakravarty, Gayatri Subramanian, Sonam Popli, Manoj Veleeparambil, Shumin Fan, Ritu Chakravarti, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Many viruses activate cellular autophagy in infected cells to facilitate their replication. Recently, we identified an interferon (IFN)-stimulated gene (ISG) Tudor domain containing 7 (TDRD7), which inhibits viral replication by blocking autophagy pathway. Here, we present a molecular mechanism for TDRD7 action and its relative contribution to protection against viral pathogenesis. TDRD7 inhibited the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a kinase required for initiating autophagy. Mechanistically, TDRD7 interacted directly with AMPK in the cytosolic compartment. Domain-mapping analyses revealed C-terminal Tudor domain of TDRD7 interacted with auto-inhibitory domain of AMPK. Deletion of Tudor domains abolished anti-AMPK and antiviral …

Unleashing The Potential Of 1,3-Diketone Analogues As Selective Lh2 Inhibitors, Juhoon Lee, Hou-Fu Guo, Shike Wang, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Zhifeng Jing, Rae M. Sammons, Eun Jeong Cho, Pengyu Ren, G. Andrés Cisneros, Jonathan M. Kurie, Kevin N. Dalby

Markey Cancer Center Faculty Publications

Lysyl hydroxylase 2 (LH2) catalyzes the formation of highly stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus promoting lung cancer metastasis through its capacity to modulate specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening (HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1−18, and identified 12 and 13 that inhibit LH2 with IC50’s of approximately 300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum mechanics/molecular mechanics (QM/MM) modeling indicates that the selectivity of 12 and 13 may stem from …

A Genomics Driven Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Julia Draper, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat S. Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Posters

Acute lymphoblastic leukemia in infants (iALL) is a high-risk subtype of childhood leukemia, with poor survival outcomes despite intensive therapies. Rearrangement of KMT2A (KMT2A-r) on chromosome 11q23 is the most frequent cytogenetic abnormality in iALL, occurring in 70% of cases. KMT2A-r is associated with chemotherapy resistance, early relapse, and rapid leukemic progression, all of which contribute to poor survival outcomes. The most common KMT2A-r in iALL is KMT2A::AFF1 (MLL::AF4), derived from t(4;11)(q21;23) and arises in utero as shown in multiple clinical studies. Infant ALL’s cell of origin is thought to be a very early hematopoietic precursor, with transcriptomic studies of …

Rare Complications Associated With Use Of Bovine Pericardium, Mohamed Aashiq Abdul Ghayum, Nitin Madan, William Gibson, Sanket Shah

Posters

Background Bovine Pericardium (BP), with numerous and improving preparation techniques, has been used extensively for over 50 years in repair of simple and complex congenital heart defects. It has several advantages over other surgical materials. However, there is a paucity of data in the pediatric population regarding complications associated with BP. Herein, we report two rare complications noted with BP use. Case Description Case 1. A 14-month-old male, with trisomy 21 and complete Atrioventricular canal defect, repaired using BP. A routine surveillance echocardiogram showed a mass attached to the atrial septum and atrial aspect of the left atrioventricular valve (Figure …

Renal Cell Carcinoma With Fibromyomatous Stroma Has A Distinctive Staining Pattern With Gata3 And Cd133 From Clear Cell Rcc And Clear Cell Papillary Rcc (Ccp-Rcc), Brandon Metcalf, Jining Feng, Leilei Chen, Vaishali Pansare, Ping L. Zhang

Conference Presentation Abstracts

Context: Renal cell carcinoma with fibromyomatous stroma (RCC-FMS) is a provisional entity of renal cell neoplasm that can be difficult to distinguish from low-grade clear cell RCC and clear cell papillary renal cell carcinoma (CCP-RCC) owing to its fibromyomatous stroma, low-grade nuclei, and clear cell cytoplasm.

Design: In this pilot study, we evaluated the utility of GATA3 and CD133 (a stem cell marker) as immunostain markers for the standard panel of cytokeratin 7 (CK7), CD10, and CAIX in distinguishing RCC-FMS from clear cell RCC and CCP-RCC. We stained 6 RCC-FMSs, 5 clear cell RCCs, and 5 CCP-RCC samples for all …

Monoclonal Immunoglobulin-Associated Glomerulopathy: Single Health Center Experience With 16 Cases, Brandon Metcalf, Yazan A. Al-Othman, James Huang, Wei Li, Hassan D. Kanaan, Ping L. Zhang

Conference Presentation Abstracts

Context: In addition to monoclonal cryoglobulinemic glomerulopathy, nonorganized monoclonal immunoglobulin (Ig) can deposit in glomeruli, causing either proliferative glomerulonephritis or membranous glomerulopathy. We present our experience related to this phenomenon.

Design: Sixteen cases of monoclonal immunoglobulin-associated glomerulopathy (MIAGN) from 14 patients were identified during the past 13 years and their pathologic and clinical features were collected and presented.

Results: One case of membranous glomerulopathy with monoclonal immunoglobulin deposits (MGNMID) (also called membranous glomerulopathy with light-chain–restricted deposits) was found. The patient was a 71-year-old woman with serum creatinine at 0.7 mg/dL and nephrotic syndrome (urine protein to creatinine ratio at 5.41), …

Igm-Dominant Immune Complex-Mediated Glomerulonephritis Should Be Classified As Membranoproliferative Glomerulonephritis, Igm Subtype, Sarang Khan, Brandon Metcalf, Wei Li, Hassan Kanaan, Ping L. Zhang

Conference Presentation Abstracts

Context: Immunoglobulin M (IgM) glomerulopathy usually presents as drug-resistant nephrotic syndrome and is characterized by diffuse effacement of foot processes and scattered mesangial IgM deposits, which is considered within the spectrum of minimal change disease and primary focal segmental glomerulosclerosis. However, IgM-dominant immune complex–mediated glomerulonephritis (IgM-ICMGN) is a rare renal entity and usually characterized by a membranoproliferative pattern with light microscopy; dominant IgM staining by immunofluorescent staining; and subendothelial, mesangial, and occasional subepithelial deposits by electron microscopy.

Design: We report our experience of 5 IgM-ICMGN cases with their pathologic phenotypes and clinical scenarios.

Results: Patient ages ranged from 47 to …

Combined Smad4 And Imp3 Immunohistochemical Stains To Increase The Probability Of Diagnosing Pancreatic Adenocarcinomas In Fine-Needle Biopsies, Reenal Patel, Ashbita Pokharel, Ping L. Zhang, Zhenhong H. Qu

Conference Presentation Abstracts

Context: SMAD4 and IMP3 are useful stains in diagnosing pancreatic cancer but not perfect to reach that goal individually. We attempted to determine if using both SMAD4 and IMP3 can increase the diagnostic specificity of fine-needle biopsies (FNBs) for pancreatic adenocarcinomas, as FNBs often showed limited tissue for the morphologic evaluation.

Design: Fifteen FNBs with or without prior cytology were evaluated with both SMAD4 and IMP3 stains. Nuclear loss of SMAD4 was graded as 0 (no loss), 1–2+ (partial loss), and 3+ (total loss), whereas IMP3 was graded 0–3+ by staining intensity. Staining results were correlated with morphologic changes for …

Doac Therapy Associated With Macroscopic Hematuria: Investigation Of The Underlying Urologic Etiologies, Catherine Xie, Mary Wyrzykowski, Subhash Edupuganti, Ming Xie

Conference Presentation Abstracts

Context: Direct oral anticoagulants (DOACs) have gained wide use in prevention and treatment of thromboembolic diseases. Both major and nonmajor bleeding events have been reported. Hematuria is a common bleeding complication in patients receiving DOACs.

Design: This study retrospectively investigates the underlying urologic etiologies responsible for DOAC therapy–related macroscopic hematuria. During a 1-year period, hospitalized patients with prolonged PTT and DOAC therapy–related hemorrhage were identified. Medical chart review focused on urology consult and related laboratory and imaging findings.

Results: Among 93 patients with DOAC therapy–related hemorrhage, 15 had macroscopic hematuria (16%), including 11 men and 4 women with a median …

Using An Artificial Intelligence (Ai) Tool (Chatgpt) To Identify The Main Indications And Side Effects Of Drugs In Patient Medical Records, Mai Elzieny, Zhenhong Qu

Conference Presentation Abstracts

Context: Drug history is important clinical information for the correct histologic diagnosis of a wide variety of nonneoplastic diseases, such as hepatitis, gastritis, and colitis. As pathologists, however, keeping a strong knowledge of all drugs (and variations of drug names) can be challenging. Using online databases to find relevant drug information one at a time is very time-consuming.

Design: Sixty-seven drugs were collected from the medical records of 5 randomly selected patients. ChatGPT (https://chat.openai.com/chat) was instructed to identify (1) the main clinical indications, and (2) the major side effects of each drug, using the prompt “List the major indications and …

“It's So Expensive And Isn’T Any Better! Or Is It?” A Comparative Analysis Of Price Per Ecmo Hour, Intracranial Hemorrhage, And Survival Rates In Neonates On Bivalirudin Vs. Heparin, Johanna I. Orrick, Jessie Charbonneau, Kari L. Davidson, Alexandra Oschman, John M. Daniel Iv

Posters

Background: Heparin has been the anticoagulant of choice for Neonatal ECMO for the past thirty years. It has the benefit of being well studied and having a low production cost. As bivalirudin is a newer anticoagulant, it has not been as widely studied and has a higher production cost, many centers are concerned about changing to a newer, more expensive agent. Bivalirudin has been studied from both an efficacy and cost perspective in adult patients (Sun et al 2021) and pediatric VAD populations (Burnstein et al 2023). While some safety and efficacy data exist for neonates, there are few if …

Neutrophilic Panniculitis Associated With Myelodysplastic Syndrome/Myeloproliferative Neoplasm: A Case Report And Literature Review, Alexa J. Cohen, Laura K. Gleason, Safiyyah A. Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP.

CASE PRESENTATION: A 65-year-old woman with MDS/MPN presented for evaluation of painful and pruritic nodules on her upper and lower extremities. A biopsy …

A Shorter Door-In-Door-Out Time Is Associated With Improved Outcome In Large Vessel Occlusion Stroke., Adam Sigal, Derek L Isenberg, Chadd K Kraus, Daniel Ackerman, Joseph Herres, Ethan S Brandler, Alexander Kuc, Jason T Nomura, Derek R Cooney, Michael T Mullen, Huaqing Zhao, Nina T Gentile

Einstein Health Papers

Introduction: Endovascular thrombectomy (EVT) significantly improves outcomes in large vessel occlusion stroke (LVOS). When a patient with a LVOS arrives at a hospital that does not perform EVT, emergent transfer to an endovascular stroke center (ESC) is required. Our objective was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in patients undergoing EVT. Methods: We conducted an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry of 2,400 LVOS patients treated at nine ESCs in the United States. We examined the association between DIDO times and 90-day outcomes as measured by the …

Recovery Of Lung Function After 149 Days On Extracorporeal Membrane Oxygenation For Covid-19, Orlando R Suero, Sri Kartik Valluri, Mario H Farias-Kovac, Leo Simpson, Gabriel Loor, Diana M Guerra, Jose L Diaz-Gomez, Subhasis Chatterjee

The Texas Heart Institute Journal

This report highlights survival and the patient’s perspective after prolonged venovenous extracorporeal membrane oxygenation (ECMO) for COVID-19–related respiratory failure.

A 36-year-old man with COVID-19 presented with fever, anosmia, and hypoxia. After respiratory deterioration necessitating intubation and lung-protective ventilation, he was referred for ECMO. After 3 days of conventional venovenous ECMO, he required multiple creative cannulation configurations. Adequate sedation and recurrent bradycardia were persistent challenges. After 149 consecutive days of ECMO, he recovered native lung function and was weaned from mechanical ventilation.

This represents the longest-duration ECMO support in a survivor of COVID-19 yet reported. Necessary strategies included unconventional cannulation and …

Optimized Catheter System Demonstrates Utility For Endomyocardial Delivery Of Cardiopoietic Stem Cells In Target Patients With Heart Failure, Jozef Bartunek, Andre Terzic

The Texas Heart Institute Journal

No abstract provided.

St-Segment Elevation Myocardial Infarction And Bleeding Complications In Jak2-Negative Polycythemia, Priscilla Duran Luciano, Vanessa Sabella-Jiménez

The Texas Heart Institute Journal

Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the JAK2 gene. Because of their hypercoagulable state and risk of hemorrhage, patients with polycythemia vera who present with an acute myocardial infarction pose a challenge to physicians. This case report describes the presentation and treatment of a Hispanic patient with JAK2 V617F-negative primary polycythemia who developed cardiac arrest and ST-segment elevation myocardial infarction owing to complete occlusion of the left anterior descending artery as well as bleeding complications and postmyocardial pericarditis.

Kneiffiella Palmae: A Non-Aspergillus Fungal Infection Isolated From A Pulmonary Nodule In A Child With Chronic Granulomatous Disease, Bianca E. Ituarte, Connie Canete-Gibas, Nathan P. Wiederhold, Liset Olarte

Manuscripts, Articles, Book Chapters and Other Papers

We report the first known human case of Kneiffiella palmae in the medical literature. K. palmae was isolated from a pulmonary nodule in a 7-year-old male with chronic granulomatous disease. The mold was identified as K. palmae at a national reference laboratory, where 17 other human respiratory samples tested positive for K. palmae from 2013 to 2021. Optimal antimicrobial treatment is unknown, but azoles and amphotericin B demonstrated in vitro activity against each tested isolate.

Validation Of A Clinical Prediction Rule For Distinguishing Bacterial And Aseptic Meningitis In Pediatric Patients, Amelia L Gurley, Matt Fukuda, Ashwin Sharma, Ethan Lee, Erica Junqueira, Michael Kang, Tommy Y Kim

Children’s Nutrition Research Center Staff Publications

Introduction

The treatments and prognosis of bacterial meningitis differ greatly from those of aseptic meningitis, making early identification and differentiation essential. Several different clinical prediction rules have been developed to distinguish bacterial meningitis from aseptic meningitis. We sought to validate one clinical prediction rule for pediatric patients utilizing a centralized data warehouse that collects daily data from 184 hospitals across the United States.

Methods

We retrospectively collected data on all patients aged 29 days to 14 years who presented to Hospital Corporation of America (HCA) Healthcare hospitals from January 1, 2016, to May 31, 2021, with a diagnosis of meningitis. …

Stop-Bang Questionnaire For Screening Obstructive Sleep Apnea Syndrome Among Hypertensive Patients In Kenya, Salim Abdallah, Jasmit Shah, Jumaa Bwika, Sayed Karar

Internal Medicine, East Africa

Introduction: Obstructive sleep apnea (OSA) is a type of breathing problem during sleep caused by the blockage of the upper airway, which can cause cessation of airflow. There is limited research on the prevalence of OSA in hypertensive patients in sub-Saharan Africa (SSA). The study aimed to describe the prevalence and clinical characteristics of OSA among hypertensive patients at a tertiary hospital in Nairobi, Kenya.

Methods: This cross-sectional study was conducted at the Aga Khan University Hospital in Nairobi, Kenya. Two hundred and fifty-one hypertensive patients were screened for OSA risk using the STOP-Bang questionnaire (SBQ). Patients with a SBQ …

Kenyan Palliative Care Providers’ And Leaders’ Perceptions Of Palliative Care Research Needs And Support To Facilitate Rigorous Research, K. Cartmell, E. Doherty, Nancy Gikaara, Z. Ali, S. Qanungo, E. S. Melikam, R. A. Powell

Internal Medicine, East Africa

Background: Palliative care (PC) can reduce symptom distress and improve quality of life for patients and their families experiencing life-threatening illness. While the need for PC in Kenya is high, PC service delivery and research is limited. Qualitative research is needed to explore potential areas for PC research and support needed to enable that research. This insight is critical for informing a national PC research agenda and mobilizing limited resources for conducting rigorous PC research in Kenya.

Objectives: To explore perceptions of priority areas for PC research and support needed to facilitate rigorous research from the perspective of Kenyan PC …

Gall Bladder Schistosomiasis Diagnosed Incidentally Post Laparoscopic Cholecystectomy: A Case Report, Willbroad Kyejo, Sajida Panjwani, Ally Zain Ismail, Blessing Mathew, Caroline Ngimba, Ally Mwanga

Internal Medicine, East Africa

Introduction and importance: Schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma. It primarily affects the intestines, liver, and urinary tract however, rare cases have been reported where the parasite invades other organs. This case report presents an incidental finding of schistosomiasis, upon histopathology evaluation, in a patient who underwent laparoscopic cholecystectomy for symptomatic gallstone disease with recurrent attacks of cholecystitis.

Case presentation: We present the case of a 42-year-old female patient who presented to the emergency department with symptoms and signs suggestive of acute cholecystitis. She underwent conservative management with interval laparoscopic cholecystectomy …

Closing The Gap For Children With Ocd: A Staged-Care Model Of Cognitive Behavioural Therapy With Exposure And Response Prevention, Lara J Farrell, Allison M Waters, Eric A Storch, Gabrielle Simcock, Iain E Perkes, Jessica R Grisham, Katelyn M Dyason, Thomas H Ollendick

Center for Medical Ethics and Health Policy Staff Publications

Childhood obsessive-compulsive disorder (OCD) is among the most prevalent and disabling mental health conditions affecting children and adolescents. Although the distress and burden associated with childhood OCD are well documented and empirically supported treatments are available, there remains an unacceptable "treatment gap" and "quality gap" in the provision of services for youth suffering from OCD. The treatment gap represents the large number of children who never receive mental health services for OCD, while the quality gap refers to the children and young people who do access services, but do not receive evidence-based, cognitive behavioural therapy with exposure and response prevention …

Emotional Distress And Cardiovascular Disease Risk Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Gladys Crespo-Ramos, Ionut Bebu, Heidi Krause-Steinrauf, Claire J Hoogendoorn, Ran Fang, Dominic Ehrmann, Caroline Presley, Aanand D Naik, Aimee Katona, Elizabeth A Walker, Andrea Cherrington, Jeffrey S Gonzalez

Faculty, Staff and Student Publications

AIMS: People with type 2 diabetes (T2DM) have an increased risk of cardiovascular disease (CVD). We examined depressive symptoms (DS) and diabetes distress (DD) in relation to the estimated 10-year risk of CVD in adults with T2DM enrolled in the GRADE Emotional Distress Substudy.

METHODS: Linear regression models examined the associations of baseline DS and DD with estimated 10-year risk of CVD using the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, adjusting for age, sex, race/ethnicity, education, income, diabetes duration, diabetes-related complications, and HbA1c.

RESULTS: A total of 1,605 GRADE participants were included: 54% Non-Latino (NL) White, 18% Latino, 19% NL-Black, …

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …

Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah

Faculty, Staff and Student Publications

No abstract provided.

Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and …