Medical Specialties Commons^™

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

A Phase 2 Randomized Trial Of Nbi-1065846 (Tak-041) In Patients With Anhedonia Associated With Major Depressive Disorder: Results Of The Terpsis Study, Shannon R Benedetto, Adrian Ionescu, Tingting Ge, Maura Furey, Swan Lin, Manish K Jha, Andrew Krystal, Asim A Shah, David P Walling, Neel Shah, Sakina J Rizvi, Sidney Kennedy, Antonio Laurenza, Venkatesha Murthy, Eiry Roberts, Jaskaran B Singh

Faculty, Staff and Students Publications

Background: Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models.

Methods: TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression …

Experiences Of Emotional Support Among Parents Of Children And Adolescents With Type 1 Diabetes: A Qualitative Study, Sahar S Eshtehardi, Marissa N Baudino, Barbara J Anderson, Deborah I Thompson, David G Marrero, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Parents of youth with type 1 diabetes (T1D) experience substantial disease-specific demands and distress, yet their perceptions about the emotional support they receive related to the challenges of caring for a child with diabetes have not been well described. This research aimed to characterize the types of emotional support parents of youth with T1D receive and how they experience emotional support.

Methods: As part of a larger qualitative study on diabetes health-related quality of life, 23 parents (96% mothers) of youth with T1D (M age = 10.9 ± 3.8 years; 35% female) completed semi-structured interviews about various aspects of …

Superior Vena Cava And Atrial Cardiomyopathy: Role Of Adjunctive Superior Vena Cava Isolation Ablation In Atrial Fibrillation, Bharat K Kantharia, Xander H T Wehrens, Dominik Linz

Faculty, Staff and Students Publications

No abstract provided.

Pancrelipase Treatment Of Exocrine Pancreatic Insufficiency Due To Chronic Pancreatitis: Rationale And Methodology Of A Real-World, Prospective, Observational Study, Mohamed O Othman, Jens J Kort, Tamas A Gonda, Guru Trikudanathan, Darshan J Kothari, Walter Park, Luis F Lara, Moming Li, Diala Harb

Faculty, Staff and Students Publications

No abstract provided.

Women And Kidney Health: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Giorgina Barbara Piccoli, Sofia B Ahmed, Fadi Fakhouri, Vesna D Garovic, Michelle A Hladunewich, Shilpanjali Jesudason, Jai Prakash, Angela C Webster, Elena Zakharova, Michael Cheung, Jennifer M King, Michel Jadoul, Wolfgang C Winkelmayer, Christina M Wyatt

Faculty, Staff and Students Publications

The KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference on Women and Kidney Health was convened to identify key sex and gender issues in kidney care, practices for optimizing healthcare in women with kidney diseases, and priorities for future research. Participants emphasized the importance of addressing the influence of sex and gender in diagnosis, risk assessment, prognosis, and treatment of chronic kidney disease (CKD) and its complications, as well as considering issues across the lifespan (puberty, sexual and reproductive health, menopause). CKD is a risk factor for adverse pregnancy outcomes with every type of kidney disease and severity. All women …

Atrial Fibrillation In Advanced Ckd: To Anticoagulate, Or Not, And With What?, Muhammad S Ajmal, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

No abstract provided.

Patient-Centered Management Of Heavy Menstrual Bleeding While On Anticoagulation: A Survey Study, Benjamin Barnett, Rushad Patell, Dana Angelini, Leben Tefera, Jordan K Schaefer, Ang Li, Alejandra Gutierrez Bernal, Shruti Chaturvedi, Anjlee Mahajan, Leslie Lake, Jori May, Anna L Parks

Faculty, Staff and Students Publications

Background: Nearly three-quarters of women experience heavy menstrual bleeding (HMB) during anticoagulation treatment for venous thromboembolism (VTE). HMB can lead to medical interventions, impact school or work and diminish quality of life (QOL). While there are several management options for HMB in patients with VTE, we lack information on how patients approach HMB treatment decisions.

Objectives: We examined patients' experience with, perceptions of, and preferences for treatment of HMB while on anticoagulation.

Methods: Clinicians and patient advocates developed a web-based survey that was distributed via patient advocacy organizations and social media between May and June 2024, targeting participants 18 years …

Ideal Navitor Implant Depth For Redo-Tavr Feasibility And Coronary Access: A Ct Simulation Study, Sahil Khera, Syed Zaid, Parasuram Krishnamoorthy, Anoop N Koshy, Sneha Gudibendi, Megan Berdan, Lucy M Safi, Stamatios Lerakis, George D Dangas, Samin K Sharma, Annapoorna S Kini, Gilbert H L Tang

Faculty, Staff and Students Publications

Background: The impact of implant depth of the Abbott Navitor intra-annular, self-expanding valve on redo-transcatheter aortic valve replacement (TAVR) feasibility is unknown.

Objectives: The authors sought to determine the feasibility of redo-TAVR and coronary access with Edwards Sapien 3 (S3) valve after initial Navitor valve, based on various implant depths on computed tomography (CT) simulation.

Methods: Using 2050 pre-TAVR CTs of patients with native aortic stenosis, initial Navitor TAVR simulations were done at 3 implant depths (0 mm, 3 mm, and 5 mm), with frame expansion assumed at native annular dimensions and commissural alignment not achievable. Redo-TAVR with S3 was …

Cardiogenic Shock With Acute Myocardial Infarction Among Older Adults In The United States, Taha Mansoor, Ali Bin Abdul Jabbar, Mahmoud Ismayl, Dylan Yu, Kartik Gupta, Sachin Parikh, Austin Brubaker, Abdul Mannan Khan Minhas, Dmitry Abramov, Jagadeesh Kalavakunta, Vishal Gupta, Salim S Virani, Santhosh K G Koshy

Faculty, Staff and Students Publications

Background: Characteristics and outcomes associated with cardiogenic shock (CS) with acute myocardial infarction (AMI) in older patients have not been well characterized.

Objectives: The purpose of this study was to investigate characteristics and outcomes of older patients admitted with CS with AMI.

Methods: We used the National Inpatient Sample database to evaluate clinical characteristics of hospitalizations, clinical outcomes, and health care utilization of hospitalizations of older patients ≥80 years with CS and AMI from 2003 to 2021. We also compared data from older patients with a reference relatively younger patient population (18-79 years).

Results: During the study period, 207,333 hospitalizations …

A Multi-Institutional Multi-Methods Analysis Of Jeopardy Systems In Academic Hospital Medicine, Kirsten N Kangelaris, Angela Keniston, Andrew D Auerbach, Gregory Bowling, Marisha Burden, Shradha A Kulkarni, Luci K Leykum, Anne S Linker, Matthew Sakumoto, Jeffrey Schnipper, Gopi Astik

Faculty, Staff and Students Publications

Background: Hospital medicine programs use backup ("jeopardy") systems to cover unexpected staffing gaps, but little is known about their structures or optimal practices.

Objectives: To describe jeopardy structures, assess clinician perceptions, and identify potential approaches across a broad sample of hospital medicine groups.

Methods: This multi-methods study, conducted within a national hospitalist consortium, used virtual focus groups and an email survey to (1) describe the presence and structure of jeopardy systems and (2) explore features perceived as fair, equitable, and tolerable. Rapid qualitative analysis identified major themes, while descriptive methods analyzed survey data.

Results: Twenty-five individuals participated in focus groups, …

A Fascination With Gastrointestinal Viruses, Mary Kolb Estes

Faculty, Staff and Students Publications

My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements …

Evaluation Of A Novel Tc-24 Recombinant Antigen Elisa For Serologic Detection Of Trypanosoma Cruzi Infection In Dogs: A Pilot Study, Rojelio Mejia, Guilherme G Verocai, Ilana A Mosley, Ashley B Saunders, Bin Zhan, Lindsey Vongthavaravat, Rachel E Busselman, Sarah A Hamer

Faculty, Staff and Students Publications

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a significant challenge for canine health, with limited diagnostic tools. This study assessed the performance of a novel Tc-24 recombinant antigen ELISA compared to three commercial diagnostic tests on 70 serum samples from kennel dogs in Texas. The Tc-24 ELISA demonstrated high sensitivity (87.5%) and specificity (91.2%) compared to Indirect Fluorescent Antibody (IFA) testing, with significant differences in Tc-24 optical density (OD) between positives and negatives (0.607 vs. 0.089, p < 0.001). When compared to Chagas Stat-Pak (SP), Tc-24 ELISA showed sensitivity and specificity values of 82.1% and 86.7%, respectively (p < 0.001). For Chagas Detect Plus (IB), the assay achieved a sensitivity of 80.0% and specificity of 93.1% (p < 0.001). Spearman correlation analysis revealed significant associations between Tc-24 OD and SP (r = 1.0, p = 0.0167), IB (r = 0.9, p = 0.0833) and IFA (r = 0.6273, p = 0.044). Elevated immunochromatographic values in commercial kits (SP or IB) correlated with Tc-24 OD (1.17 vs. 0.039, p < 0.001), achieving 100% sensitivity and 95.8% specificity based on positive results from commercial kits. These findings suggest that Tc-24 ELISA is a reliable and accurate serological tool for diagnosing T. cruzi infection in dogs, with the potential to enhance diagnostic capabilities in veterinary medicine.

Elephant Endotheliotropic Herpesvirus 2 Infection In 5 African Elephants (Loxodonta Africana) At Multiple North American Zoological Institutions, Taylor J Willis, Anne Burgdorf-Moisuk, Maren Connolly, Jan Raines, Cameron Ratliff, Zoltan S Gyimesi, Erica Lipanovich, Genevive A Dumonceaux, Kathryn L Perrin, Lauren L Howard, Matthew E Kinney, Kirk Suedmeyer, Erin Latimer, Tiffany L Kim, Jessica R Watts, Jie Tan, Paul Ling

Faculty, Staff and Students Publications

Objective: To acknowledge that elephant endotheliotropic herpesvirus (EEHV) is a well-recognized major threat to Asian elephants (Elephas maximus) and can cause acute and often fatal hemorrhagic disease (HD). Historically, EEHV-HD has been less frequently identified in African elephants (Loxodonta africana). This case series describes 5 recent cases of EEHV2 infection in African elephants within managed care at 5 North American institutions.

Animals: 5 African elephants (L africana).

Clinical presentation: The cases involved 4-, 7-, and 10-year-old males that died despite receiving aggressive medical therapy and 4- and 14-year-old females that survived. Clinical signs included lethargy, decreased appetite, lameness, changes in …

Treatment Of Cutaneous Collagenous Vasculopathy With Pulsed Dye Laser, Hannah L Hanania, Isabella Camacho-Hubbard, Zeena Y Nawas

Faculty, Staff and Students Publications

Objectives: Cutaneous collagenous vasculopathy (CCV) is a rare, idiopathic microangiopathy marked by widespread telangiectasias and histologic vessel wall thickening. Due to its rarity and clinical overlap with other vascular conditions, CCV poses diagnostic and therapeutic challenges. This report highlights the successful use of pulsed dye laser (PDL) therapy in treating a case of extensive CCV.

Methods: A 40-year-old woman with a decade-long history of progressive telangiectasias involving the extremities, trunk, and forearms underwent treatment with a 595-nm PDL. Six treatment sessions were conducted over 14 months.

Results: The patient experienced significant improvement in erythema, telangiectasias, and associated discomfort, with sustained …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

Spatial Omics Enters The Microscopic Realm: Opportunities And Challenges, Yichen Si, Joo Sang Lee, Goo Jun, Hyun Min Kang, Jun Hee Lee

Faculty, Staff and Students Publications

Spatial transcriptomics (ST) enables systematic profiling of whole-transcriptome gene expression in tissues while preserving spatial context. Recent advances in sequencing- and imaging-based ST technologies have ushered in the era of microscopic-resolution ST (μST), allowing transcriptome mapping at cellular and even subcellular scales with unprecedented precision. Despite these advances, μST faces substantial challenges, including sparse transcript discovery per submicron (or micron)-sized spatial units and data fragmentation across platforms, hindering integration and analysis. There is also a growing demand for scalable, segmentation-free, and universally applicable analysis methods, as well as strategies for 3D mapping, multi-omics integration, and artificial intelligence (AI)-driven spatial analysis. …

From Imaging To Impact: A Multi-Disciplinary T32 Program Framework And Initial Insights For Training In Image-Guided Cancer Therapy, Kari J Brewer Savannah, Stephen Y Lai, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

As multi-disciplinary image-guided assessment and therapies become increasingly important for precision oncology, the need for comprehensive training opportunities that effectively prepare the next generation of clinician-scientists and scientists is evident. We present an innovative, evidence-based research training framework that integrates the following critical features: 1) intentional and personalized mentoring and career development, 2) immersive research in image-guided cancer therapy, 3) strategic mentored clinical exposure, 4) structured didactic learning and professional development opportunities, and 5) mentored grant writing. Designed to foster scientific rigor, translational thinking, and multi-disciplinary collaboration, the Image-Guided Cancer Therapy T32 Training Program (IGCT-T32) aims to prepare postdoctoral fellows …

Biomarkers For The Diagnosis Of Indeterminate Pulmonary Nodules: Are We There Yet?, Kevin C Mcgann, Timothy A Khalil, Michael N Kammer, Edwin J Ostrin, Harvey I Pass, Jun-Chieh James Tsay, Leopoldo N Segal, Melissa Potter, Stephen A Deppen, Fabien Maldonado, Eric L Grogan

Faculty, Staff and Student Publications

Indeterminate pulmonary nodules (IPNs), which are nodules that cannot be classified as definitively benign or malignant at the time of detection, are now diagnosed on the order of millions per year. Management of IPNs remains heavily debated, and routine practice ultimately involves some balance of overall clinical risk assessment and additional diagnostic tests or procedures which may generate significant risk, cost, and worry. Biomarkers are biologically based tests or indicators capable of accurately characterizing the physiologic properties of homeostasis and disease that are not otherwise easily evaluated by the clinician. Accurate biomarkers thereby serve as reliable surrogates for biological aberrancy, …

Expression Graph Network Framework For Biomarker Discovery, Yang Liu, Jason Huse, Kasthuri Kannan

Faculty, Staff and Student Publications

Biomarker discovery for complex diseases, such as cancer, hinges on uncovering molecular signatures that capture intricate, interconnected relationships within biological data-a challenge that traditional statistical and machine learning methods often fail to meet due to the complexity of high-dimensional gene expression profiles. To overcome this, we introduce the expression graph network framework (EGNF). This cutting-edge graph-based approach integrates graph neural networks with network-based feature engineering to enhance the predictive identification of biomarkers. EGNF constructs biologically informed networks by combining gene expression data and clinical attributes within a graph database, utilizing hierarchical clustering to generate dynamic, patient-specific representations of molecular interactions. …

Auprc: A Metric For Evaluating The Performance Of In-Silico Perturbation Methods In Identifying Differentially Expressed Genes, Hongxu Zhu, Amir Asiaee, Leila Azinfar, Jun Li, Han Liang, Ehsan Irajizad, Kim-Anh Do, James P Long

Faculty, Staff and Student Publications

In silico perturbation models, computational methods that can predict cellular responses to perturbations, present an opportunity to reduce the need for costly and time-intensive in vitro experiments. Many recently proposed models predict high-dimensional cellular responses, such as gene or protein expression to perturbations such as gene knockout or drugs. However, evaluating in silico performance has largely relied on metrics such as $R^{2}$, which assess overall prediction accuracy but fail to capture biologically significant outcomes like the identification of differentially expressed (DE) genes. In this study, we present a novel evaluation framework that introduces the AUPRC metric to assess the precision …

Whole-Genome Sequence-Based Association Analysis Of African American Individuals With Bipolar Disorder And Schizophrenia, Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon Lefaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A Mccarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott

Faculty, Staff and Student Publications

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of …

Cross-Platform Transcriptomic Data Integration Identifies An Overactive Neuro-Immune Signature In Human Osteoarthritis Synovium, Michael D Newton, Hannah Swahn, Dana E Orange, Joseph B Lesnak, Theodore J Price, Anne-Marie Malfait, Rachel E Miller, Martin K Lotz, Tristan Maerz

Faculty, Staff and Student Publications

Objective: Chronic synovitis is associated with osteoarthritis (OA) pain, but the molecular underpinnings remain unclear. Our objective was to characterize the transcriptional phenotype of OA synovium with a focus on signaling relevant to pain.

Design: Eight publicly-available microarray and RNA-sequencing GEO datasets from human non-OA and OA subjects underwent quality control and re-analysis for differentially-expressed genes (DEGs). Cross-platform statistical integration was performed via a weighted Z-test to combine detection power across datasets. Gene set enrichment, cell type enrichment, and regulon analyses were performed. Human single-cell RNA sequencing data was used to map gene expression to cell types. Ligand-receptor interactions were …

Deciphering Transcriptomic Changes In Chemobrain: A Comprehensive Review, Tusar Kanta Acharya, Yuan Pan, Peter M Grace, Cobi J Heijnen, Rajasekaran Mahalingam

Faculty, Staff and Student Publications

Chemotherapy-induced cognitive impairments (CICI), colloquially known as "chemobrain," represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital. Key mechanisms implicated in CICI include blood-brain barrier disruption, neuroinflammation, and oxidative stress as a result of various chemotherapy treatments, such as doxorubicin, cisplatin, and paclitaxel. We delve into advanced …

Whole-Genome Sequence-Based Association Analysis Of African American Individuals With Bipolar Disorder And Schizophrenia, Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon Lefaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, National Heart, Lung, And Blood Institute Trans-Omics For Precision Medicine (Topmed) Consortium;, Genomic Psychiatry Cohort Investigators, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A Mccarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott

Faculty, Staff and Students Publications

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of …

Longitudinal Meta-Cohort Study Protocol Using Systems Biology To Identify Vaccine Safety Biomarkers, Joann Diray-Arce, Ana C Chang, Sara Moradipoor, Donato Amodio, Bruce Carleton, Wan-Chun Chang, Nigel W Crawford, Meagan Karoly, Annmarie Hoch, Kerry Mcenaney, Tahir S Kafil, Mahitha Donthireddy, Sarah K Steltz, Simon D Van Haren, Asimenia Angelidou, Kinga K Smolen, Hanno Steen, Jessica Lasky-Su, Huyen Tran, Peter Liu, C Buddy Creech, Clare L Cutland, Helen Petousis-Harris, Ishac Nazy, Rae S M Yeung, Sonali Kochhar, Steve Black, Nicholas Wood, Dale Nordenberg, Paolo Palma, Inna G Ovsyannikova, Richard B Kennedy, Gregory A Poland, Al Ozonoff, Robert T Chen, Ofer Levy, Karina A Top, International Network Of Special Immunization Services (Insis) Members

Faculty, Staff and Students Publications

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g., transcriptomics, proteomics, metabolomics) through a global consortium of clinical networks, leading immunology, pharmacogenomics teams to uncover the molecular mechanisms behind AEFIs. The network ensures accurate and standardized data collection and analysis through rigorous data management and quality assurance processes. INSIS also implements harmonized case definitions and protocols for collecting …

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

Ras-Membrane Interaction And Oligomerization: There Is More Than Meets The Eye, Abraham C Sianoya, Vijay K Bhardwaj, Alemayehu A Gorfe

Faculty, Staff and Student Publications

Membrane association is fundamental to Rat sarcoma (RAS) function, driving both its physiologic signaling and oncogenic transformation. This review consolidates recent advances in the study of RAS-membrane interactions, emphasizing the molecular mechanisms underlying its membrane engagement and oligomerization. We first discuss the roles of RAS lipid modification and conformational diversity of its intrinsically disordered C-terminus in these processes, and we then examine the debate surrounding RAS dimerization and its potential role in the formation of higher-order oligomers. By integrating emerging insights into these issues, we offer our own perspectives on the driving forces of RAS oligomerization and propose potential new …