Medical Specialties Commons^™

Wandering Spleen In A Pediatric Lung Transplant Patient With Filamin A Deficiency: An Incidental Finding, Savannah Ellis Knight, Mayel Yepez Donado, Maria Carolina Gazzaneo

Faculty, Staff and Students Publications

Background: Filamin A (FLNA) deficiency is a known cause of progressive lung disease and need for pediatric lung transplant; however, what may be less well known to lung transplant providers are the extrapulmonary complications of FLNA deficiencies, such as wandering spleen. We present a patient who underwent a lung transplant for FLNA deficiency and later developed posttransplant abdominal pain.

Case presentation: An 11-year-old female who had previously undergone a bilateral lung transplant due to FLNA deficiency, causing progressive lung disease, presented with abdominal pain and diarrhea. The patient's stool was tested for causes of gastroenteritis using a gastrointestinal pathogen panel …

De Novo Pathogenic Csf1r Variant Implicates Microglial Dysfunction In Pathogenesis Of Febrile Infection-Related Epilepsy Syndrome, Kristen S Fisher, Jesse M Levine, Alexander Ankar, Ruizhi Duan, Yi Chen Lai, Eyal Muscal, Sarah R Risen, James J Riviello, Pei-Chien Tsai, Daniel G Calame

Faculty, Staff and Students Publications

Febrile infection-related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus following a febrile illness with resulting refractory epilepsy. Evidence supports the presence of immune dysregulation in patients with FIRES, but a monogenic basis for FIRES has not been identified in most cases. We present a case of a previously healthy 16-year-old male with FIRES who was found to have a de novo predicted damaging missense variant in CSF1R on clinical whole genome sequencing, a gene encoding a critical regulator of microglial homeostasis in which pathogenic variants cause adult onset leukoencephalopathy. Molecular modeling demonstrates that the CSF1R variant …

Cmr Findings In The Long-Term Outcomes After Multisystem Inflammatory Syndrome In Children (Music) Study, Sean M Lang, Dongngan T Truong, Andrew J Powell, Valiantsina Kazlova, Jane W Newburger, Jordan D Awerbach, Edem Binka, Tamara T Bradford, Mark Cartoski, Andrew Cheng, Michael P Dilorenzo, Audrey Dionne, Adam L Dorfman, Matthew D Elias, Olukayode Garuba, Jennifer F Gerardin, Keren Hasbani, Pei-Ni Jone, Christopher Z Lam, Nilanjana Misra, Lerraughn M Morgan, Arni Nutting, Jyoti K Patel, Joshua D Robinson, Eleanor L Schuchardt, Kristen Sexson Tejtel, Gautam K Singh, Timothy C Slesnick, Felicia Trachtenberg, Michael D Taylor, Music Study Investigators

Faculty, Staff and Students Publications

Background: Multisystem Inflammatory Syndrome in Children is characterized by high rates of acute cardiovascular involvement with rapid recovery of organ dysfunction. However, information regarding long-term sequelae is lacking. We sought to characterize the systolic function and myocardial tissue properties using cardiac magnetic resonance (CMR) imaging in a multicenter observational cohort of patients with Multisystem Inflammatory Syndrome in Children.

Methods: In this observational cohort study, comprising 32 centers in North America, CMR studies were analyzed by a core laboratory to assess ventricular volumetric data, tissue characterization, and coronary involvement.

Results: A total of 263 CMRs from 255 patients with Multisystem Inflammatory …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Generation Of Induced Pluripotent Stem Cell Lines (Rfsci003-A, Rfsci004-A) From Monozygotic Twins Discordant For Age-Related Macular Degeneration, Naresh Rajendran, Wendy Runyon, Sam Hu, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

2d Speckle Tracking Strain Echocardiography In Multisystem Inflammatory Syndrome In Children: A Multicenter Analysis From The Music Study, Francesca Sperotto, Valiantsina Kazlova, Felicia L Trachtenberg, Dongngan T Truong, Sanjeev Aggarwal, Joseph R Block, Tamara T Bradford, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese M Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean M Lang, Carol A Mcfarland, Elizabeth C Mitchell, Elias Moussi Saad, Todd T Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie K Votava-Smith, Hunter C Wilson, Jane W Newburger, Kevin G Friedman

Faculty, Staff and Students Publications

Background: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes.

Methods: We performed an ambi-directional, 32-center cohort study on hospitalized patients with MIS-C (March 2020-November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant).

Results: Of 349 patients (median age, 8.7 years [interquartile …

Critical Care Cadets: A Serious Game For Managing Mechanical Ventilation, Daniel Hassumani, Satid Thammasitboon, Fong Lam, Aarti Bavare, Moushumi Sur, Shelley Kumar, Thomas Reeves, Brian Rissmiller

Faculty, Staff and Students Publications

Background: Pediatric critical care medicine (PCCM) fellows require proficiency in mechanical respiratory support and ventilator management strategies. Traditional training methods have limitations, and there is a need to expedite the learning process. Serious games have emerged as effective supplements to traditional teaching methods, promoting knowledge acquisition through immersive and engaging experiences. However, there is a void in the context of complex decision making in mechanical ventilation management.

Objective: To develop a serious game to enhance the knowledge and practical strategies of PCCM fellows in mechanical ventilation management.

Methods: The game was designed on the basis of theory-informed design principles and …

Intracranial Rhizomucor Pusillus Mucormycosis In An Adolescent Triggering A Stroke Alert: A Case Report And A Systematic Review Of Pediatric Cases, Rima El Atrache, Melissa Mizerik, Joaquin Francisco Ruiz Lopez, Eric Engstrom, Karla Patricia Salazar, Mikael C Guzman-Karlsson, Daniel Davila-Williams, Sonali Sen, Kristen S Fisher, Jennifer C Erklauer

Faculty, Staff and Students Publications

Mucormycosis is a rare, life-threatening opportunistic infection primarily affecting immunocompromised patients. The available literature on Rhizomucor pusillus (R pusillus) infections of the central nervous system (CNS) in children is very limited. We present the case of an immunocompromised adolescent with intracranial mucormycosis due to R pusillus manifesting with stroke-like symptoms. This case highlights this rare condition's diagnostic complexity and management challenges. We include a review of the available literature on pediatric R pusillus CNS infections to increase awareness among health care providers.

Clinical Phenotype And Outcomes In Autoimmune Encephalitis After Herpes Simplex Virus Encephalitis: A Systematic Review And Meta-Analysis, Jonathan Cleaver, Renetta Chungath, Amy Gimson, Christine Strippel, Bryan Ceronie, Babak Soleimani, Thomas Johnson, Eyal Muscal, Kristen Fisher, Yike Jiang, Timothy A Erickson, Kristy O Murray, Siv Tonje Faret Hovet, Charlotte Aaberg Poulsen, Anna Søgaard Magnussen, Pauline Dumez, Shannon Ronca, Martin Häusler, Annegret Quade, Andrew Swayne, Morten Blaabjerg, Mette Nissen, Alexander J Sandweiss, Jerome Honnorat, Russell Dale, Ming Lim, Michael Eyre, Margherita Nosadini, Lahiru Handunnetthi, Sarosh R Irani, Adam E Handel

Faculty, Staff and Students Publications

Background: Autoimmune encephalitis after herpes simplex virus encephalitis (HSVE-AE) represents the intersection of central nervous system infection and autoimmunity. Defining the phenotype and the safety and effectiveness of immunotherapy in HSVE-AE would help identify immunotherapy candidates, optimise therapeutic strategies, and improve patient outcomes.

Methods: We systematically searched Embase, Medline, PubMed, and Web of Science (2007-2024) for cases meeting consensus criteria for AE after confirmed HSVE. Demographics, phenotype, treatment and outcome data were extracted. Dimensionality reduction, network analysis, and multivariate logistic regression was used to explore age- and diagnosis-specific patterns and outcome predictors.

Results: From 2259 articles screened, 78 studies (225 …

Changes In Child Placement After Child Abuse Pediatrics Consultation For Suspected Physical Abuse, Kristine A Campbell, Antoinette L Laskey, Daniel M Lindberg, M Katherine Henry, Porcia Vaughn, James D Anderst, Megan M Letson, Angela N Bachim, Nancy S Harper, Carmen M Coombs, Lori D Frasier, Joanne N Wood

Faculty, Staff and Students Publications

Background: The association between child abuse pediatric (CAP) assessments and child welfare outcomes is unknown.

Objective: To determine the association between a CAP determination of the likelihood of physical abuse and change in child placement. We hypothesized that child race would be associated with CAP determination of abuse likelihood and child welfare outcomes.

Participants and setting: Children under age ten years with in-person CAP consultation and referral to child protective services for suspected physical abuse at a U.S. pediatric referral center participating in CAPNET, a CAP research network, from 02/2021 to 01/2023.

Methods: We created a series of generalized estimating …

Wound-Healing And Onboard Care During Long-Duration Human Deep Space Exploration From A Surgical Perspective Through The Lens Of A Scoping Review, Dora Babocs, Krishi Korrapati, Cooper Lytle, Monika L Gloviczki, Gustavo S Oderich, M Mark Melin, Rowena Christiansen

Faculty, Staff and Students Publications

Objective: The aim of this study was to develop a bridge between the fields of aerospace medicine and vascular surgery, and to emphasize the need for leading experts in vascular medicine, interventional radiology, and surgery to address the critical human spaceflight research gaps highlighted by the National Aeronautics and Space Administration (NASA).

Methods: A scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on literature published between 2000 and 2024. A well-defined search strategy was employed for keyword searches across multiple databases, including PubMed, Scopus, Cochrane, Embase, the NASA Life Science Data Archive, …

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 …

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 …

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 …

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 …

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. …

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 …

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 …

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 …