Digital Commons Network^™

Somatostatin Receptor 2 Overexpression In Hepatocellular Carcinoma: Implications For Cancer Biology And Therapeutic Applications, Servando Hernandez Vargas, Solmaz Aghaamiri, Jack T Adams, Tyler M Bateman, Belkacem Acidi, Sukhen C Ghosh, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Majid Momeny, Ali Azhdarinia

The Brown Foundation: Institute of Molecular Medicine

Background: Somatostatin receptor 2 (SSTR2), a G protein-coupled receptor, is overexpressed in multiple malignancies, including hepatocellular carcinoma (HCC). While SSTR2 has traditionally been viewed as an inhibitory receptor involved in suppressing hormone secretion and cell proliferation, emerging evidence suggests a more complex role in cancer biology. However, the functional implications of SSTR2 expression in HCC remain poorly understood. This study aimed to systematically investigate the molecular landscape associated with SSTR2 expression in HCC and evaluate its potential as a therapeutic target.

Methods: SSTR2 expression patterns across 22 tumor types were assessed using TNMplot, and its expression in HCC was further …

Pediatric Epilepsy Surgery: The Noninvasive Presurgical Evaluation, Deepankar Mohanty, Michael Quach

Faculty, Staff and Students Publications

Background: Drug-resistant epilepsy is a debilitating condition that afflicts individuals across all demographics, including children. The only recourse for many of these individuals is neurosurgery to reduce seizure burden, by either resecting or ablating the cerebral source or modulating it with a stimulator device. In either case, a thorough presurgical evaluation is required to identify brain regions of interest and construct an appropriate surgical plan. The scope of this evaluation has grown rapidly over the years as new and refined techniques have emerged. The aim of this article was to condense the most salient points regarding investigational tools used commonly …

Infusion Of Blood From Young And Old Mice Modulates Amyloid Pathology, Matias Pizarro, Ruben Gomez-Gutierrez, Ariel Caviedes, Catalina Valdes, Ute Woehlbier, Cristian Vargas, Mauricio Hernandez, Claudia Duran-Aniotz, Rodrigo Morales

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of misfolded proteins in the brain. Recently, the impact of blood components in the progression of this disease has come to attention. This study investigates the effects of infusing blood from young and old wild-type mice into transgenic mice that model AD brain amyloidosis. Impaired memory and Aβ accumulation were observed in mice infused with blood from old donors. A proteomic analysis in the brain of these mice identified alterations in components related to synaptogenesis and the endocannabinoid system. The α2δ2 protein, associated with neuronal calcium regulation, was validated …

Loss Of Ptdss1 In Tumor Cells Improves Immunogenicity And Response To Anti-Pd-1 Therapy, Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma

Faculty, Staff and Student Publications

PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the …

Distinct Transcriptional Regulation Of The Wnt And Tgfβ Signaling Families Associated With Wound Healing And Fibrotic Outcomes To Lens Injury, Catherine Lalman, Kylie R. Stabler, Joshua Disatham, Lisa A. Brennan, Marc Kantorow, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Posterior capsule opacification (PCO) is a fibrotic complication of cataract surgery caused by aberrant repair of residual lens cells. It remains unclear how the lens injury response shifts toward a pathological repair process. Here, we performed a transcriptional analysis of two major pro-fibrotic pathways, the TGF-β superfamily and Wnt signaling pathways to determine how they are differentially regulated during regenerative wound healing versus fibrosis in a lens injury model. For these studies, RNA sequencing was performed on an ex vivo lens explant system that models post-surgical healing within regenerative and fibrotic microenvironments, from 0 to 3 days post-injury. Fibrotic conditions …

An Analysis Of Gamma-Aminobutyric Acid Levels With Structural And Functional Connectivity In Antipsychotic Medication-Naïve First Episode Psychosis Patients, Genelle Dano Samson

All ETDs from UAB

Schizophrenia is a complex psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and abnormalities in emotional expression, social interaction, and motivation. Cognitive deficits and alterations in perception are core features of psychosis spectrum disorders, though the neurobiological bases of these impairments are not thoroughly understood. Examination of the structures responsible for cognition, along with how their connectivity and neurochemistry are altered in psychosis, is crucial to understanding and treating schizophrenia. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system and plays a crucial role in the regulation of neuronal activity. Evidence from animal models and postmortem …

Identifying The Neurobiological Substrates Of Gulf War Illness, Chloe Lisette Jones

All ETDs from UAB

Gulf War Illness (GWI) affects approximately 30% of veterans who served in the 1991 Persian Gulf War and is characterized by chronic pain and fatigue, as well as cognitive, mood, gastrointestinal, and respiratory symptoms. Animal research has suggested that GWI is caused by a combination of neurotoxicants such as nerve gas, anti-nerve agent pills, and pesticides, though a definitive pathophysiological model has not been established. In this human observational study, 20 veterans with GWI and 20 healthy Gulf War veterans (HV) underwent whole-brain magnetic resonance spectroscopy (MRS) to non-invasively measure several metabolites associated with neuroinflammation. Whole blood was also collected …

A High-Salt Diet Modulates Renal Afferent Nerve Activity; Potential Role Of The Endothelin System, Jiaxi Shen

All ETDs from UAB

Hypertension is a prevalent disease around the world. Increased blood pressure leads to a higher risk of stroke and coronary heart disease. Diet, lifestyle, and gene regulation are potential causative factors, and salt-sensitive hypertension is one common types of hypertension. In response to a high-salt diet, blood pressure may elevate with increasing risks of cardiovascular disease (CVD). Endothelin-1, which binds to endothelin A (ETA) and B (ETB) receptors, is strongly involved in controlling the blood vessels and sensory nerve signaling pathway between the kidney and the central nervous system during high salt dietary challenge. The function of the ETB receptor …

Myelin Mapping In Psychosis, Victoria Lynn King

All ETDs from UAB

It is well established that myelin in the central nervous system is an axonal insulator which speeds the conduction velocity of action potentials. However, its role in the cortex has also been shown to support metabolic demands and aid in cortical plasticity. Myelin develops throughout childhood and adolescence from sensorimotor areas to association areas and peaks during adolescence. Importantly, this is the same time that psychosis-spectrum disorders (PSDs) begin to present clinically; thus, given the critical role of myelination in shaping the mature cortex, disruptions in this process – particularly during adolescence – are thought to partially explain the onset …

Impact Of Alpha-Synuclein Aggregation On Corticostriatal Synaptic Function And Morphology, Charlotte Franziska Brzozowski

All ETDs from UAB

Lewy Body Dementias (LBDs), including Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB), are defined by α-synuclein (α-syn) accumulation in Lewy Pathology (LP). LP is abundant in cortical layer V intratelencephalic (IT) neurons, a subset of neurons that also degenerate in the pre-supplementary motor area (preSMA) in humans, which is homologous to the secondary motor cortex (M2) in mice, as observed in PD postmortem tissue. IT neuron projections to the striatum are an intrinsic part of the motor basal ganglia circuitry, believed to modulate cognitive aspects of executive motor control, such as updating motor plans. M2 projections to …

Amygdala Npy+ Interneurons Are Activated By Aversive Stim-Uli, Patric Perez

All ETDs from UAB

Neuropeptide Y (NPY) serves as a critical endogenous anxiolytic and stress-buffering molecule, yet the temporal and spatial dynamics of NPY+ cells during fear learning re-main unknown. Temporal dynamics can be measured with in vivo calcium imaging tech-niques, which enable real-time monitoring of cell-type-specific neural activity in freely behaving animals. Snapshots of neuronal activation can be measured using c-Fos im-munohistochemistry, thereby providing excellent spatial resolution. Here, I employ cut-ting-edge approaches to characterize the temporal and spatial activation patterns of NPY+ cells in amygdala, a key fear-regulating brain region negatively impacted by aversive events. I first used in vivo fiber photometry, together …

Understanding Psychotic Disorders Using Normative Modeling-Derived Individual-Level Brain Structural Abnormalities, Natalie Remiszewski

All ETDs from UAB

Psychosis is an heterogenous condition that occurs in many psychiatric disorders. It has a variable symptom presentation and recent initiatives have suggested that investigating the underlying neurobiology of psychiatric disorders rather than their symptomatology would provide a more accurate picture for diagnosis, prognosis, and treatment. Grey matter has been implicated in the pathophysiology of psychosis and psychotic disorders, though significant natural variation due to age and sex have impeded the distinction of pathologically relevant grey matter abnormalities in psychosis. Additionally, case-control approaches to exploring grey matter abnormalities in psychotic disorders often obscure subtle variation in individuals. Here, we utilize a …

Murder On The Axonal Express: Synucleinopathy Disruption Of 14-3-3 Protein-Protein Interactions Impairs Axonal Trafficking, Frank Sanders Pair

All ETDs from UAB

14-3-3s are a family of proteins highly expressed in the brain. These proteins exert their functions mainly through protein-protein interactions (PPIs) and have thousands of binding partners. 14-3-3s have been shown to be present in pro-teinaceous aggregates of alpha-synuclein (αsyn), a pathological hallmark of synucleinopathies. This includes such diseases as Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). 14-3-3 proteins, particularly the 14-3-3θ isoform, have been shown to be protective in multiple synucleinopathy models. However, reduced soluble levels of 14-3-3s and increased phosphorylation of 14-3-3θ at S232 observed in synucleinopathies like DLB may impair their protec-tive ability, potentially due …

Nmr-Based Metabolomic Profiling For Brain Cancer Diagnosis And Treatment Guidance, Julia R Zickus, José S Enriquez, Paytience Smith, Bill T Sun, Muxin Wang, Aldo Morales, Pratip K Bhattacharya, Shivanand Pudakalakatti

Faculty, Staff and Student Publications

Nuclear magnetic resonance (NMR) spectroscopy is a routinely used analytical tool for studying chemical entities of varying molecular sizes, ranging from approximately 20 Da to ~45 kDa, and in some cases even larger. Over the past two decades, the use of NMR spectroscopy has significantly expanded to the study of metabolomics. In this medium-sized review, the application of NMR-based metabolomics in the diagnosis, therapeutic intervention, and guidance of therapy for various types of brain cancer is discussed.

Complete Genome Sequence Of Actinomyces Oris Strain Mg-1: An Oral Commensal Critical For Dental Plaque Formation, Bibek G C, Kexin Tan, Chenggang Wu

Faculty, Staff and Student Publications

Actinomyces oris MG-1 is a key oral commensal involved in dental plaque formation. We report its complete genome sequence, generated using Illumina and Oxford Nanopore sequencing. The genome consists of a single circular chromosome of 3,042,829 bp, providing a resource for future functional studies.

Neurotransmitter Signaling In Molecular And Behavioral Immune Responses To Pathogens In C Elegans, Benson Otarigho, Alejandro Aballay

Faculty, Staff and Student Publications

Neurotransmitter signaling pathways play major roles in both molecular and behavioral defenses against pathogen invasion, shaping the ability of Caenorhabditis elegans to sense and respond to environmental challenges. Given the conservation of neurotransmitter signaling pathways, their understanding may not only provide insights into the neurobiology of C. elegans but also has broader implications for our understanding of neural-immune interactions and host defense mechanisms in higher organisms. In this review, we discussed the literature on various neurotransmitter signaling pathways, including serotonergic, dopaminergic/octopaminergic, GABAergic, and glutamatergic pathways, and how these pathways modulate molecular and behavioral immune defense against pathogens.

The Glutaminase Activity Of Asns Fuels Glutamine Metabolism In Leukemia, Wai-Kin Chan, Lin Tan, Sara A Martinez, Di Du, Thomas D Horvath, Michael Pontikos, Leona A Rusling, Yulun Chiu, Bao Q Tran, Susan B Rempe, Sergei Sukharev, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Not available.

Barriers And Timely Postoperative Radiation Therapy In Head And Neck Cancer, Megan T Nguyen, Emily Kistner-Griffin, Reid Demass, Bhisham S Chera, Chanita Hughes Halbert, Katherine R Sterba, Elizabeth G Hill, Brian Nussenbaum, Anthony J Alberg, Vlad C Sandulache, David J Hernandez, Ryan S Jackson, Sidharth V Puram, Russel Kahmke, Nosayaba Osazuwa-Peters, Gail Jackson, Sue S Yom, Evan M Graboyes

Faculty, Staff and Students Publications

Importance: Initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is associated with improved outcomes among patients with head and neck squamous cell carcinoma. However, the relationship of barriers to care with timely PORT is unknown.

Objective: To categorize barriers to timely PORT, evaluate the association of barriers to care with initiation of timely PORT, and describe the primary reason for delay among patients without timely PORT.

Design, setting, and participants: This prospective cohort study at a US academic medical center included adults with head and neck squamous cell carcinoma undergoing curative-intent surgery with an indication for PORT. …

The Colonic Crypt: Cellular Dynamics And Signaling Pathways In Homeostasis And Cancer, Anh L. Nguyen, Molly A. Lausten, Bruce M. Boman

College of Life Sciences Faculty Papers

The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting Epithelial-Mesenchymal Transition (EMT). The colonic crypt is a highly structured epithelial unit that functions in maintaining homeostasis through a complex physiological function of diverse cell types: SCs, transit-amplifying (TA) progenitors, goblet cells, absorptive colonocytes, Paneth-like cells, M cells, tuft cells, and enteroendocrine cells. These cellular subpopulations are spatially organized and regulated by multiple crucial signaling pathways, including …

Longitudinal Associations Of Epigenetic Aging With Cognitive Aging In Hispanic/Latino Adults From The Hispanic Community Health Study/Study Of Latinos, Myriam Fornage, Wassim Tarraf, Rui Xia, Adriana Ordonez, Tamar Sofer, Freddie Márquez, Bharat Thyagarajan, Gregory A Talavera, Linda C Gallo, Charles Decarli, Hector M González

The Brown Foundation: Institute of Molecular Medicine

Due to the paucity of longitudinal DNA methylation data (DNAm), especially among Hispanic/Latino adults, the association between changes in epigenetic clocks over time and cognitive aging phenotypes has not been investigated. This longitudinal study included 2671 Hispanic/Latino adults (57 years; 66% women) with blood DNAm data and neurocognitive function assessed at two visits ~7 years apart. We evaluated the associations of 5 epigenetic clocks and their between-visit change with multiple measures of cognitive aging that included a global and domain-specific cognitive function score at each visit, between-visit change in global and domain-specific cognitive function score, and MCI diagnosis at visit …

Structure Of The T9ss Porkn Ring Complex Reveals Conformational Plasticity Based On The Repurposed Fge Fold, Xiangan Liu, John D Perpich, Liqiang Song, Christian Cambillau, Thierry Doan, Lei Zheng, Richard J Lamont, Eric Cascales, Bo Hu

Faculty, Staff and Student Publications

The type IX secretion system (T9SS) is a protein secretion machinery unique to the Bacteroidetes-Chlorobi-Fibrobacteres superphylum, which plays crucial roles in bacterial pathogenesis and gliding motility. It is composed of >15 proteins, including the proton-motive force-dependent PorLM motor, the PorKN ring anchored to the outer membrane, and the Sov translocon. Here, we present the cryo-electron microscopy (EM) structure of the PorKN ring complex from Porphyromonas gingivalis at 3.2 Å resolution. Our structural analysis reveals that PorK contains a repurposed formylglycine-generating enzyme-like fold, which serves as a structural hub for complex assembly rather than enzymatic activity. The complex exhibits a 33-fold …

Retinoid-X-Receptor As A Mediator Of Poststroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Hematogenous Macrophages, Shun-Ming Ting, Xiurong Zhao, Guanghua Sun, Mercedes Ricote, Jaroslaw Aronowski

Faculty, Staff and Student Publications

After stroke, microglia and hematogenous macrophages, together referred to as MΦ, clear dead cells and cellular debris in the infarcted brain through phagocytosis as an essential part of the recovery process. However, the phagocytic capability of MΦ declines with age. Furthermore, aged MΦ become overactivated in response to stroke, enhancing secondary brain injury. In this study, we demonstrated that by reversing the age-related dysfunctions in MΦ through activating the retinoid X receptor (RXR), the recovery after stroke in the aged brain could be improved. Using RNA-sequencing, we compared the transcriptomes between MΦ isolated from the brains of young and aged …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

Bypassing Bamd Essentiality By Mutations In A Non-Essential Substrate, Santosh Kumar, Anna Konovalova

Faculty, Staff and Student Publications

The β-barrel assembly machinery (Bam) is essential for assembling all transmembrane β-barrel outer membrane proteins in gram-negative bacteria. The Bam complex consists of the central β-barrel protein BamA and accessory Bam lipoproteins, including the widely conserved and essential BamD. BamD is assumed to be an essential regulator of OMP assembly, as its absence causes a global defect in OMP biogenesis. Here, we challenge this view by demonstrating that BamD essentiality is both conditional and substrate specific. In Escherichia coli, its function can be bypassed by preventing BamA jamming by a single, non-essential substrate RcsF. Our findings suggest that BamD …

Inhibition Of The Ufd-1-Npl-4 Complex Triggers An Aberrant Immune Response In Caenorhabditis Elegans, Rajneesh Rao, Alejandro Aballay, Jogender Singh

Faculty, Staff and Student Publications

The UFD-1 (ubiquitin fusion degradation 1)-NPL-4 (nuclear protein localization homolog 4) heterodimer is involved in extracting ubiquitinated proteins from several plasma membrane locations, including the endoplasmic reticulum. This heterodimer complex helps in the degradation of ubiquitinated proteins via the proteasome with the help of the AAA+ATPase CDC-48. While the ubiquitin-proteasome system is known to have important roles in maintaining innate immune responses, the role of the UFD-1-NPL-4 complex in regulating immunity remains elusive. In this study, we investigate the role of the UFD-1-NPL-4 complex in maintaining

The Role Of Ceramides As Biomarkers And Therapeutic Targets For Cardiometabolic Disease And Its Intersection With Cellular Aging, Youssef Moustafa Shalaby

Thesis/ Dissertation Defenses

Ceramides (Cer), a subclass of sphingolipids with potent bioactive properties, have gained recognition as key players in the pathogenesis of cardiometabolic diseases (CMD). They modulate critical cellular functions such as apoptosis, inflammation, insulin signaling, and oxidative stress. This dissertation explores the dual role of Cer as both early diagnostic markers and therapeutic targets, bridging clinical insights with mechanistic understanding through a combination of human and experimental studies.

A highly sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify intracellular levels of specific Cer species, including CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1. This method was translated into …

Whole Genome Sequence Analysis Of Low-Density Lipoprotein Cholesterol Across 246 K Individuals, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Eric Van Buren, Sara Haidermota, Darina Postupaka, Whitney Hornsby, Joshua C Bis, Jennifer A Brody, Brian E Cade, Ren-Hua Chung, Joanne E Curran, Scott M Damrauer, Lisa De Las Fuentes, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Mariaelisa Graff, Xiuqing Guo, Bertha A Hidalgo, Lifang Hou, Ryan Irvin, Renae Judy, Rita R Kalyani, Tanika N Kelly, Iain R Konigsberg, Brian G Kral, Lydia Coulter Kwee, Daniel Levy, Changwei Li, Ani W Manichaikul, Lisa Warsinger Martin, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Alex P Reiner, Svati H Shah, Roelof A J Smit, Jennifer A Smith, Kent D Taylor, Hemant Tiwari, Michael Y Tsai, Satupa'itea Viali, Zhe Wang, Yuxuan Wang, Wei Zhao, Donna K Arnett, John Blangero, Eric Boerwinkle, Donald W Bowden, Jenna C Carlson, Yii-Der Ida Chen, Patrick T Ellinor, Myriam Fornage, Jiang He, Nancy Heard-Costa, Robert C Kaplan, Sharon L R Kardia, Charles Kooperberg, William E Kraus, Leslie A Lange, Ruth J F Loos, Braxton D Mitchell, Bruce M Psaty, Daniel J Rader, Susan Redline, Stephen S Rich, Lisa R Yanek, Richard Gibbs, Stacey Gabriel, Karine A Viaud-Martinez, Susan K Dutcher, Soren Germer, Ryan Kim, Jerome I Rotter, Xihong Lin, Gina M Peloso, Pradeep Natarajan

The Brown Foundation: Institute of Molecular Medicine

Background: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability.

Results: Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Direct Oral Anticoagulant Transition Strategies Using Anti-Xa Concentrations Upon Intensive Care Unit Admission, Mariah I Sigala, Corey V Dinunno, Chelsea N Lopez, Luma Succar, Jenny H Petkova, Edward A Graviss, Duc T Nguyen, Kevin R Donahue

Faculty, Staff and Students Publications

Background: The increased utilization of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of FXaI-specific anti-Xa concentrations. Critically ill populations are at risk of bleeding secondary to FXaI accumulation in the setting of end-organ dysfunction. To mitigate this risk, an FXaI anti-Xa concentration-guided approach to transitioning between oral and parenteral anticoagulation has been explored.

Objective: To compare the incidence of bleeding upon intensive care unit (ICU) admission between 2 different FXaI transition strategies: concentration versus non-concentration-guided.

Methods: We performed a retrospective chart review of patients admitted between January 2019 and May 2022 with …

Fetal Body Composition And Organ Growth In Pregnancies Complicated By First-Trimester Vaginal Bleeding Status: Nichd Fetal 3d Study, Alexandra Jean-Louis, Jessica L Gleason, Zhen Chen, Kathryn A Wagner, Dian He, Roger Newman, William A Grobman, Robert Gore-Langton, Seth Sherman, Magdalena Sanz Cortes, Edward K Chien, Luis F Goncalves, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objective

This study aimed to explore associations between self-reported first-trimester vaginal bleeding status and fetal body composition and organ volumes measured by three-dimensional (3D) ultrasound across pregnancy.

Study Design

The NICHD Fetal 3D Study (2015–2019) included individuals with singleton pregnancies at low risk for fetal growth abnormalities (n = 2,634). Fetal body composition measures of arm, abdomen, and thigh, and organ volumes including cerebellum, lung, kidney, and liver, were measured up to five times between 15 and 40 weeks using 3D ultrasound. Women were grouped by cumulative days of self-reported first-trimester vaginal bleeding: 0 (no bleeding, reference), 1, or …