Digital Commons Network^™

The Senescence Associated Secretory Phenotype, A Key Marker Of Cellular Senescence, Is Elevated In Depression And Moderated By Sex, Nishika Navrange, Ana Paula Mendes-Silva, Charles F Reynolds, Julie Wetherell, Benoit Mulsant, Mary C Kimmel, Eric J Lenze, Breno Satler Diniz

2020-Current year OA Pubs

OBJECTIVE: Studies have found elevation in a key biomarker of aging (the senescence-associated secretory phenotype (SASP) index) in depression. We investigated whether sex moderates the association between the SASP and major depression in older adults.

METHODS: We included 423 older adults in a current major depressive episode and 140 adults with no history of depression. We measured the plasma levels of SASP biomarkers using multiplex immunoassays. The interaction effect between sex, depression diagnosis, and senescence markers were analyzed by general linear models, adjusted for confounding variables.

RESULTS: Individuals with depression had a higher SASP index than the healthy comparison group …

Establishment Of A Reverse Genetics System For Studying Human Immune Functions In Mice, Priya Pal, Shuai Gao, Hongbo Gao, Xiwen Qin, Marina Cella, Qiankun Wang, Liang Shan

2020-Current year OA Pubs

Reverse genetics approaches in mice are widely used to understand gene functions and their aberrations in diseases. However, limitations exist in translating findings from animal models to human physiology. Humanized mice provide a powerful bridge to understanding human physiology and mechanisms of disease pathogenesis while maintaining the feasibility of working with small animals. Methods for generating humanized mouse models that allow scientists to probe contributions of particular genes have been rudimentary. Here, we established an efficient method for generating genetically modified human cord blood-derived CD34

Advanced Minimal Residual Disease Detection Using A Novel Circulating Tumor Dna Assay: A Report Of Two Cases, Georges Azzi, Thomas P Slavin, Jesus Izaguirre-Carbonell, Hillary S Sloane, Daniel L Edelstein, Cynthia X. Ma

2020-Current year OA Pubs

INTRODUCTION: Tumor-informed minimal residual disease (MRD) monitoring assays based on plasma circulating tumor DNA (ctDNA) are increasingly integrated into the clinical management of patients with cancer. In the post-surgical curative intent setting and as an adjunct to radiographic imaging for response assessment and surveillance, timely identification of MRD may better guide therapeutic decision-making. The increasing clinical adoption of MRD testing, supported by a growing body of evidence demonstrating its potential utility at critical decision points across diverse tumor histology, has brought attention to the variability in the analytical performance of available ctDNA assays. This variability is becoming increasingly appreciated as …

Networked Behaviors Associated With A Large-Scale Secure Messaging Network: Cross-Sectional Secondary Data Analysis, Laura Rosa Baratta, Linlin Xia, Daphne Lew, Elise Eiden, Y Jasmine Wu, Noshir Contractor, Bruce L Lambert, Sunny S Lou, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: Communication among health care professionals is essential for effective clinical care. Asynchronous text-based clinician communication-secure messaging-is rapidly becoming the preferred mode of communication. The use of secure messaging platforms across health care institutions creates large-scale communication networks that can be used to characterize how interaction structures affect the behaviors and outcomes of network members. However, the understanding of the structure and interactions within these networks is relatively limited.

OBJECTIVE: This study investigates the characteristics of a large-scale secure messaging network and its association with health care professional messaging behaviors.

METHODS: Data on electronic health record-integrated secure messaging use from …

A Single High-Zinc Activation Enhancer Can Control Two Genes Oriented Head-To-Head In Caenorhabditis Elegans, Hanwenheng Liu, Brian Earley, Adelita Mendoza, Patrick Hunt, Sean Teng, Daniel Luke Schneider, Kerry Kornfeld

2020-Current year OA Pubs

Enhancers play critical roles in gene expression, but a full understanding of their complex functions has yet to be defined. The cellular response to excess zinc levels in Caenorhabditis elegans requires the HIZR-1 transcription factor, which binds the high-zinc activation (HZA) enhancer in the promoters of multiple target genes. Cadmium hijacks the excess zinc response by binding and activating HIZR-1. By analyzing the genome-wide transcriptional response to excess zinc and cadmium, we identified two positions in the genome where head-to-head oriented genes are both induced by metals. In both examples, a single predicted HZA enhancer is positioned between the two …

Mtor Signaling Regulates The Development Of Airway Mucous Cell Metaplasia Associated With Severe Asthma, Katrina M. Kudrna, Luis F. Vilches, Evan M. Eilers, Shailendra K. Maurya, Steven L. Brody, Amjad Horani, Kristina L. Bailey, Todd A. Wyatt, John D. Dickinson

2020-Current year OA Pubs

In asthma, airway epithelial remodeling is characterized by aberrant goblet cell metaplastic differentiation accompanied by epithelial cell hyperplasia and hypertrophy. These pathologic features in severe asthma indicate a loss of control of proliferation, cell size, differentiation, and migration. MTOR is a highly conserved pathway that regulates protein synthesis, cell size, and proliferation. We hypothesized that the balance between MTOR and autophagy regulates mucous cell metaplasia. Airways from individuals with severe asthma showed increased MTOR signaling by RPS6 phosphorylation, which was reproduced using an IL-13-activated model of primary human airway epithelial cells (hAEC). MTOR inhibition by rapamycin led to a decrease …

Beliefs About The Causes And Treatment Of Common Mental Illnesses And Suicidality In Rural Uganda, Yang Jae Lee, Rita Mbabazi, Ondine Jevremov, Shakira Nakaweesi, Ella Brodey, Jason Wykoff, Roshan Sivakumar, Rauben Kazungu, Ibrahim Ssekalo, Robert Rosenheck, Alexander C Tsai

2020-Current year OA Pubs

BACKGROUND: Mental illnesses constitute a large and escalating portion of the global burden of disease, particularly in low- and middle-income countries like Uganda. Understanding community perceptions towards mental illness is crucial for developing effective interventions.

AIMS: To explore beliefs about the perceived causes and treatment of common mental illnesses (depression, anxiety, alcohol use disorder) and suicidality in rural eastern Uganda.

METHOD: Qualitative study using 31 in-depth interviews and 4 focus group discussions with healthcare workers, community health workers, community leaders and general community members in Buyende District, Uganda. Vignettes were used to depict mental illnesses to elicit perceptions, and data …

Cord Blood Proteomics Identifies Biomarkers Of Early-Onset Neonatal Sepsis, Leena B. Mithal, Mark E. Becker, Ted Ling-Hu, Young Ah Goo, Sebastian Otero, Aspen Kremer, Surya Pandey, Nicola Lancki, Yawei Li, Yuan Luo, William Grobman, Denise Scholtens, Karen K. Mestan, Patrick C. Seed, Judd F. Hultquist

2020-Current year OA Pubs

BACKGROUNDSymptoms of early-onset neonatal sepsis (EOS) in preterm infants are nonspecific and overlap with normal postnatal physiological adaptations and noninfectious pathologies. This clinical uncertainty and the lack of reliable EOS diagnostics results in liberal use of antibiotics in the first days to weeks of life, leading to increased risk of antibiotic-related morbidities in infants who do not have an invasive infection. METHODSTo identify potential biomarkers for EOS in newborn infants, we used unlabeled tandem mass spectrometry proteomics to identify differentially abundant proteins in the umbilical cord blood of infants with and without culture-confirmed EOS. Proteins were then confirmed using immunoassay, …

Total Synthesis And Biological Activity Of "Carbamorphine": O-To-Ch2 Replacement In The E-Ring Of The Morphine Core Structure, Sota Akiyama, Rohini S Ople, Alexander Kremsmair, Nokomis Ramos-Gonzalez, Thomas Nedungadan, Brandon J Kennedy, Kevin Appourchaux, Shainnel O Eans, Bowen A Tsai, Christina Kraml, Xi-Ping Huang, Jay P Mclaughlin, Susruta Majumdar, Richmond Sarpong

2020-Current year OA Pubs

Morphine is a µ-opioid receptor (MOR) agonist and potent analgesic. However, it displays several side effects including respiratory depression and addiction. Here, we show that a single heavy atom replacement in the morphine core structure (O to CH

Involvement Of Microglia In Retinal Ganglion Cell Injury Induced By Iop Elevation In A Rat Ex Vivo Acute Glaucoma Model, Taimu Sato, Makoto Ishikawa, Yukitoshi Izumi, Naoya Shibata, Kota Sato, Michiko Ohno-Oishi, Hiroshi Tawarayama, Hiroshi Kunikata, Charles F Zorumski, Toru Nakazawa

2020-Current year OA Pubs

No abstract provided.

Vaccination Against Influenza Viruses Annually: Renewing Or Narrowing The Protective Shield?, Hanover C Matz, Ali H Ellebedy

2020-Current year OA Pubs

Annual vaccines are recommended for the seasonal influenza virus. While yearly updates to the vaccine are necessary due to the constant evolution of influenza viruses, some studies have suggested repeat vaccination may result in a reduction in vaccine effectiveness in subsequent years. This review examines the available evidence that repeated annual influenza virus vaccination may have effects on future vaccine responses, and it synthesizes the available data with studies that may indicate potential immunological mechanisms underlying these effects. The goal is to examine the available literature to determine whether these mechanisms can be subverted to improve seasonal influenza virus vaccine …

Disruption Of A Side Portal Pathway Permits Closed-State Inactivation By Bk Β Subunit N Termini, Yu Zhou, Xiao-Ming Xia, Christopher J Lingle

2020-Current year OA Pubs

Cytosolic N termini of several BK channel β regulatory subunits mediate rapid inactivation. However, in contrast to Kv channels, inactivation does not occur via a simple, open-channel block mechanism, but involves two steps, an association step in which ion permeation is maintained (O*), then followed by inactivation (I). To produce inactivation, BK β subunit N termini enter the central cavity through a lateral entry pathway ("side portal") separating the transmembrane pore-gate domain and cytosolic gating ring. Comparison of BK conformations reveals an aqueous pathway into the central cavity in the open structure, while in the closed structure, three sequential basic …

Coresh: A Gene Signature-Based Search Engine For Public Gene Expression Datasets, Vladimir Sukhov, Aigul Nugmanova, Yury Vorontsov, Parul Mehrotra, Maksim Kleverov, Kodi Ravichandran, Maxim Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

Public data repositories like Gene Expression Omnibus (GEO) contain an extensive amount of data from hundreds of thousands of experiments, making them a valuable resource for researchers. A common scenario for utilizing this resource is to show transcriptional similarity of one's own data to a public dataset as evidence of potentially similar biology. However, when searching for such datasets, researchers are usually limited to keyword-based search, which requires having a specific hypothesis and relies on the presence of high-quality metadata in public datasets. Here, we introduce CORESH, a web server designed to systematically find GEO datasets that match a user-provided …

Loss Of Intracellular Fgf14 (Ifgf14) Increases Excitability Of Mature Hippocampal Pyramidal Neurons, Joseph L Ransdell, Yarimar Carrasquillo, Marie K Bosch, Rebecca L Mellor, David M Ornitz, Jeanne M Nerbonne

2020-Current year OA Pubs

Mutations in FGF14, which encodes intracellular fibroblast growth factor 14 (iFGF14), have been linked to spinocerebellar ataxia type 27 (SCA27), a multisystem disorder associated with deficits in motor coordination and cognitive function. Mice lacking iFGF14 (Fgf14-/-) display similar phenotypes, and we have previously shown that the deficits in motor coordination reflect reduced excitability of cerebellar Purkinje neurons, owing to a hyperpolarizing shift in the voltage-dependence of voltage-gated Na+ (Nav) current steady-state inactivation. Here, we present the results of experiments designed to test the hypothesis that loss of iFGF14 also attenuates the intrinsic excitability of mature hippocampal pyramidal neurons. Current-clamp recordings …

Highly Sensitive In Vivo Detection Of Dynamic Changes In Enkephalins Following Acute Stress In Mice, Marwa O Mikati, Petra Erdmann-Gilmore, Rose Connors, Sineadh M Conway, Jim Malone, Justin Woods, Robert W Sprung, Reid R Townsend, Ream Al-Hasani

2020-Current year OA Pubs

Enkephalins are opioid peptides that modulate analgesia, reward, and stress. In vivo detection of enkephalins remains difficult due to transient and low endogenous concentrations and inherent sequence similarity. To begin to address this, we previously developed a system combining in vivo optogenetics with microdialysis and a highly sensitive mass spectrometry-based assay to measure opioid peptide release in freely moving rodents (Al-Hasani et al., 2018, eLife). Here, we show improved detection resolution and stabilization of enkephalin detection, which allowed us to investigate enkephalin release during acute stress. We present an analytical method for real-time, simultaneous detection of Met- and Leu-enkephalin (Met-Enk …

Quantum Magnetization Exchange Through Transient Hydrogen Bond Matrix Defines Magnetic Resonance Signal Relaxation And Anisotropy In Central Nervous System, Dmitriy A Yablonskiy, Alexander L Sukstanskii

2020-Current year OA Pubs

The integrity of cellular membranes (lipid bilayers) and myelin sheaths covering axons is a crucial feature controlling normal brain structural and functional networks. Yet, in vivo evaluation of this integrity at the nanoscale level of the cellular membranes organization is challenging. Herein we explore the dual property of biological water in Central Nervous System (CNS), as one of the major stabilizing factors of cellular membranes, and the major source of MRI signal. We introduce the Basic Transient Hydrogen Bond (THB) model of the MR signal relaxation due to the quantum spin/magnetization exchanges within the THB Matrix encompassing water molecules and …

The Trapping Of Live Neutrophils By Macrophages During Infection, Kelley N Cooper, Marina Terekhova, Barbara Potempa, Ana D'Aubeterre, Jerome Timbol, Si An Chen, Antoine Dufour, Shunying Jin, Maxim N Artyomov, Jan Potempa, Juhi Bagaitkar

2020-Current year OA Pubs

Neutrophils are highly abundant in the oral mucosal tissues, and their balanced activation and clearance are essential for immune homeostasis. Here, we demonstrate that neutrophils infected with the bacterial pathogen Porphyromonas gingivalis (Pg) are captured alive by macrophages in a manner that bypasses all known receptor-ligand interactions involved in the phagocytosis of either live or dead cells. Mechanistically, upon interaction with Pg, or its protease RgpB (gingipains), live neutrophils undergo rapid remodeling of their proteomes, generating neoepitopes. N-terminomics-based proteomic profiling identified multiple RgpB cleavage sites on several azurophilic granule proteins that are translocated to the surface of live neutrophils via …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Antonina I Frolova, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Bispecific Antibodies In Follicular Lymphoma, Imran A. Nizamuddin, Nancy L. Bartlett

2020-Current year OA Pubs

Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm for multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at 2 years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige K Boneski, Hiromi Sesaki, Ruteja A Barve, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Phospho-Rpa2 Predicts Response To Platinum And Parp Inhibitors In Homologous Recombination-Proficient Ovarian Cancer, Angela Schab, Amanda Compadre, Rebecca Drexler, Megan Loeb, Kevin Rodriguez, Joshua Brill, Carmen Sandoval, Brooke Sanders, Lindsay Kuroki, Carolyn Mccourt, Andrea R. Hagemann, Premal Thaker, David Mutch, Matthew Powell, Ian S. Hagemann, Lulu Sun, Priyanka Verma, Elena Lomonosova, Dineo Khabele, Mary M. Mullen, Et Al.

2020-Current year OA Pubs

BACKGROUNDTreatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response.METHODSWe evaluated phospho-RPA2-T21 (p-RPA2) foci via immunofluorescence as a biomarker of replication stress in formalin-fixed, paraffin-embedded HGSC samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort, n = 31; validation cohort, n = 244) …

Genetic Structuring And Estimation Of Reproductive Adults In Onchocerca Volvulus: A Genome-Wide Analysis Across Hosts And Regions, Pawan Kumar, Young-Jun Choi, Kerstin Fischer, Shannon M. Hedtke, Anusha Kode, Nicholas Opoku, Lincoln Gankpala, Tony O. Ukety, Jöel Lonema Mande, Timothy J. C. Anderson, Warwick N. Grant, Peter U. Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Genomic analysis of parasites can deepen our understanding of their transmission, population structure, and important biological characteristics. Onchocerciasis (river blindness), caused by the parasitic nematode Onchocerca volvulus, involves adult worms residing in subcutaneous nodules that produce larval-stage microfilariae (mf), which are routinely detected in the skin for diagnosis. Whole-genome studies of mf are limited; most analyses have focused on the mitochondrial genome. We conducted a genome-wide analysis with 94% median nuclear genome coverage, analyzing 171, 37, and 98 mf from 16, 3, and 5 individuals from Ghana, Liberia, and the Democratic Republic of Congo, respectively. These data were used to …

Exploitable Mechanisms Of Antibody And Car Mediated Macrophage Cytotoxicity, Tianyi Liu, Alexander B Kim, Young Ah Goo, Minsoo Son, Jaenyeon Kim, Carl J Deselm, Et Al.

2020-Current year OA Pubs

Macrophages infiltrate solid tumors and either support survival or induce cancer cell death through phagocytosis or cytotoxicity. To uncover regulators of macrophage cytotoxicity towards cancer cells, we perform two co-culture CRISPR screens using CAR-macrophages targeting different tumor associated antigens. Both identify ATG9A as an important regulator of this cytotoxic activity. In vitro and in vivo, ATG9A depletion in cancer cells sensitizes them to macrophage-mediated killing. Proteomic and lipidomic analyses reveal that ATG9A deficiency impairs the cancer cell response to macrophage-induced plasma membrane damage through defective lysosomal exocytosis, reduced ceramide production, and disrupted caveolar endocytosis. Depleting non-cytotoxic macrophages using CSF1R inhibition …

Liger-Hn Phase Iii Trials Of Petosemtamab + Pembrolizumab And Petosemtamab Monotherapy In Recurrent Or Metastatic Hnscc, Jean-Pascal Machiels, Douglas Adkins, Et Al.

2020-Current year OA Pubs

Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death protein 1 and platinum-based therapies. Petosemtamab - a human, common light chain, bispecific antibody with enhanced antibody-dependent cellular cytotoxicity targeting epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) - demonstrated antitumor activity in r/m HNSCC. In many tumor types, including HNSCC, EGFR is an oncogenic driver, while LGR5 is upregulated. LGR5 can potentiate the wingless-type integration site (WNT)/β-catenin signaling pathway in response to …

Projection-Tags Enable Multiplex Projection Tracing And Multi-Modal Profiling Of Projection Neurons, Lite Yang, Fang Liu, Hannah Hahm, Takao Okuda, Xiaoyue Li, Yufen Zhang, Vani Kalyanaraman, Monique R Heitmeier, Vijay K Samineni

2020-Current year OA Pubs

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged …

Robust Photogrammetric Scalp Morphology Estimation For Functional Optical Neuroimaging, Abigail L Magee, Calamity Svoboda, Tessa G George, Alvin A Agato, Edward J Richter, Joseph P Culver, Adam T Eggebrecht

2020-Current year OA Pubs

SIGNIFICANCE: Optical functional neuroimaging relies upon accurate anatomical models to provide optimal data registration and image reconstruction.

AIM: We establish and validate a robust photogrammetric algorithm for scalp morphology that utilizes 3-dimensional (3D) imaging with a photogrammetric cap to provide individualized scalp morphology estimation through hair in the absence of magnetic resonance imaging (MRI).

APPROACH: The scalp morphology estimation uses a flexible, neoprene cap and 3D-printed photogrammetric modules with fiducials. We create a sparse scalp sampling and align the MNI152 atlas to generate the scalp morphology estimation. We used the international 10 to 20 electroencephalogram positions for alignment and calculated …

Molecular Mechanisms Of Inverse Agonism Via Κ-Opioid Receptor-G Protein Complexes, Aaliyah S Tyson, Saif Khan, Zenia Motiwala, Gye Won Han, Zixin Zhang, Mohsen Ranjbar, Daniel Styrpejko, Nokomis Ramos-Gonzalez, Stone Woo, Kelly Villers, Delainey Landaker, Terry Kenakin, Ryan Shenvi, Susruta Majumdar, Cornelius Gati

2020-Current year OA Pubs

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist. The pharmacological impact of agonist-free receptor-G protein complexes is poorly understood. Here we present biochemical evidence that certain κ-opioid receptor (KOR) inverse agonists can act via KOR-G

Landscape Of Cancer Associated Epcam Mutations: Molecular Modeling, Predictive Insights And Impact On Patient Survival, Priyanka S Dhotare, Audrey C Bochi-Layec, Timothy P Fleming, William E Gillanders, Ross M Bremner, Kailas D Sonawane, Narendra V Sankpal

2020-Current year OA Pubs

BACKGROUND: EpCAM (epithelial cell adhesion molecule) is a key regulator of epithelial cell-cell adhesion, signal transduction, tissue regeneration, and serves as a stem cell marker. It is frequently overexpressed in epithelial cancers and is linked to tumor progression, survival, and metastasis. However, the functional impact of EpCAM mutations in cancer remains poorly understood.

METHODS: To investigate the role of EpCAM mutations, we performed a comprehensive analysis of cancer cohorts from multiple genomic datasets, identifying novel somatic EpCAM mutations across diverse epithelial cancers. Using bioinformatics tools (SIFT, PolyPhen-2, Mutation Assessor) and molecular modeling, we assessed the potential impact of these mutations. …

Clinical Evaluation Of The Healgen Rapid Covid-19 Antigen Test As A Point-Of-Care Diagnostic Tool, Stephen A Young, Hua Zhang, Jose Rodriguez, David Mishkin, Ward Paine, Li Seyfried, Latisha Hargrove, Dennis L Broyles, Chermaen Lindberg, Anurag Purushothaman, Stacey House

2020-Current year OA Pubs

BACKGROUND: Development of readily available Rapid COVID-19 Antigen tests essential for promptly identifying SARS-CoV2 infection and preventing its spread.

METHODS: This study evaluated the clinical performance of the Healgen Rapid COVID-19 antigen test as a point-of-care diagnostic tool with 806 evaluable subjects who were within 6 days post-symptom onset. The results from the Healgen test were compared to the results from Emergency Use Authorization (EUA) approved SARS-CoV-2 RT-PCR tests.

RESULTS: Out of the 806 evaluable subjects, 140 tested positive and 640 tested negative for SARS-CoV-2 with the Healgen COVID-19 test, showing good agreement with the EUA RT-PCR results. There were …

High-Frequency, At-Home Monitoring Of Drug Safety And Tolerability In Clinical Trials: Results From Studies Of Fluvoxamine For Covid-19 Treatment, Eric J Lenze, Madeline Nykamp, J Philip Miller, Angela Stevens, Julia Schweiger, Torie Gettinger, Michael Yingling, Yi Zhang, Ginger E Nicol, Charles F Zorumski, Angela M Reiersen

2020-Current year OA Pubs

Clinical trials are increasingly using remote monitoring techniques at the patient's home. We conducted a secondary analysis of remote safety and tolerability monitoring from two fully-remote clinical trials that tested fluvoxamine for the acute treatment of COVID-19. Both trials assessed pulse and blood pressure daily, and one study assessed symptoms daily via Ecological Momentary Assessment. On average, patients provided data on vital signs on 93% of the study days and provided data on side effects on 81% of the study days. With respect to safety, patients taking fluvoxamine had reduced pulse rate compared to placebo, with the greatest difference-5 points-at …