Digital Commons Network^™

Barriers To And Facilitators Of Sustaining A Systemic Lupus Erythematosus (Sle) Patient Decision Aid In Regular Rheumatology Outpatient Care In The Usa, Erin E Blanchard, Allyson G Hall, Ezra Gore, Parvaneh Yaghoubi Jami, Aizhan Karabukayeva, Larry R Hearld, Shelby Gontarz, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: This study investigates the barriers to and facilitators of sustaining a decision aid (DA) tool for patients with SLE in routine rheumatology outpatient care across the USA. The DA was initially developed for assisting patients with SLE in making informed medication choices by providing personalized information on their treatment process.

Methods: We conducted semi-structured interviews with clinicians, administrators, and information technology (IT) professionals from 15 geographically diverse rheumatology clinics that participated in a large-scale DA implementation trial. Interviews were transcribed and analysed using NVivo, with thematic coding to identify key factors influencing DA sustainability.

Results: The analysis identified several …

Plasma Microbial Cell-Free Dna Sequencing For The Detection Of Kingella Kingae Pediatric Spinal Infections, Asim A Ahmed, Sarah Y Park, Matthew J Smollin, Martin S Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R Cotilla, Marian E Melish, Connie Trieu, Nazia A Kabani, Joshua Cooper, Audrey R Lloyd, David W Kimberlin, John C Arnold, Alejandro Jordan-Villegas, Lori E Patterson, Catherine E Foster, Pablo Yagupsky

Faculty, Staff and Students Publications

Background: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae .

Methods: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age < 18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis …

Ophthalmology Examinations In Children With Skull Fractures And Underlying Focal Hemorrhage, Karli Breeden, Cindy W Christian, Joanne N Wood, Gil Binenbaum, Daniel M Lindberg, Angela Bachim, Colleen J Bressler, Lori Frasier, Terra Frazier, Nicole R Johnson, Natalie Laub, Megan M Letson, Tagrid Ruiz-Maldonado, Matthew Valente, Jenna Kiely, Jan Leonard, M Katherine Henry

Faculty, Staff and Students Publications

Objectives: To assess the frequency and yield of retinal examination in children below 2 years old undergoing abuse evaluations in the setting of skull fracture(s) and small underlying intracranial hemorrhage.

Methods: This cross-sectional study used CAPNET, a multicenter child physical abuse network, to identify children below 2 years with a skull fracture(s) and intracranial injury limited to an underlying small focal intracranial hemorrhage undergoing subspeciality child abuse evaluations. Our outcomes of interest were (1) the performance of a retinal examination, (2) the identification of retinal hemorrhages, and (3) associations of clinical factors and CAPNET site with the performance of retinal …

Linking Symptom Inventories Using Semantic Textual Similarity, Eamonn Kennedy, Shashank Vadlamani, Hannah M Lindsey, Kelly S Peterson, Kristen Dams O'Connor, Ronak Agarwal, Houshang H Amiri, Raeda K Andersen, Talin Babikian, David A Baron, Erin D Bigler, Karen Caeyenberghs, Lisa Delano-Wood, Seth G Disner, Ekaterina Dobryakova, Blessen C Eapen, Rachel M Edelstein, Carrie Esopenko, Helen M Genova, Elbert Geuze, Naomi J Goodrich-Hunsaker, Jordan Grafman, Asta K Håberg, Cooper B Hodges, Kristen R Hoskinson, Elizabeth S Hovenden, Andrei Irimia, Neda Jahanshad, Ruchira M Jha, Finian Keleher, Kimbra Kenney, Inga K Koerte, Spencer W Liebel, Abigail Livny, Marianne Løvstad, Sarah L Martindale, Jeffrey E Max, Andrew R Mayer, Timothy B Meier, Deleene S Menefee, Abdalla Z Mohamed, Stefania Mondello, Martin M Monti, Rajendra A Morey, Virginia Newcombe, Mary R Newsome, Alexander Olsen, Nicholas J Pastorek, Mary Jo Pugh, Adeel Razi, Jacob E Resch, Jared A Rowland, Kelly Russell, Nicholas P Ryan, Randall S Scheibel, Adam T Schmidt, Gershon Spitz, Jaclyn A Stephens, Assaf Tal, Leah D Talbert, Maria Carmela Tartaglia, Brian A Taylor, Sophia I Thomopoulos, Maya Troyanskaya, Eve M Valera, Harm Jan Van Der Horn, John D Van Horn, Ragini Verma, Benjamin S C Wade, Willian C Walker, Ashley L Ware, J Kent Werner, Keith Owen Yeates, Ross D Zafonte, Michael M Zeineh, Brandon Zielinski, Paul M Thompson, Frank G Hillary, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Students Publications

An extensive library of symptom inventories has been developed over time to measure clinical symptoms of traumatic brain injury (TBI), but this variety has led to several long-standing issues. Most notably, results drawn from different settings and studies are not comparable. This creates a fundamental problem in TBI diagnostics and outcome prediction, namely that it is not possible to equate results drawn from distinct tools and symptom inventories. Here, we present an approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories by ranking item text similarities according to their conceptual likeness. We tested …

Psychometric Properties Of The Spanish Yale-Brown Obsessive-Compulsive Scale - Second Edition, Eric A Storch, Jessica Sc Cheng, Miranda Higham, Josselyn S Muñoz, Vanessa Zavala Cruz, Dayan Berrones, Diana P Obando, Jacey L Anderberg, Renee M Frederick, Vissente Tapia-Cuevas, Macarena Churruca Muñoz, Constanza Uribe Villar, Pablo R Moya, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Andrew D Wiese, Caitlin M Pinciotti, Melisa N Sagarnaga, Joseph F Mcguire, Ogechi C Onyeka, María B Moyano, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), Wayne K Goodman, James J Crowley

Faculty, Staff and Students Publications

The Yale-Brown Obsessive-Compulsive Scale, Second Edition (Y-BOCS-II) is an evidence-based clinician-rated measure for assessing the presence and severity of obsessive-compulsive symptoms. The Spanish version of the Y-BOCS-II has not yet been validated. The present study examines the psychometric properties of the Spanish Y-BOCS-II (Spanish-Y-BOCS-II) in adults with obsessive-compulsive disorder (OCD) who are of Hispanic/Latino ancestry. The Spanish-Y-BOCS-II was administered to 1805 adults with OCD. Participants also completed a battery of measures assessing OCD, depression, and anxiety symptoms. The internal consistency for the Symptom Checklist (Kuder-Richardson-20=0.92), Obsession Severity (α=0.87), Compulsion Severity (α=0.86), and Total Severity (α=0.92) were high. The inter-rater reliability …

Fetal Body Composition In Twins And Singletons, Jessica L Gleason, Wesley Lee, Zhen Chen, Kathryn A Wagner, Dian He, William A Grobman, Roger B Newman, Seth Sherman, Robert Gore-Langton, Edward Chien, Luis Goncalves, Katherine L Grantz

Faculty, Staff and Students Publications

Importance: An emerging paradigm attributes third-trimester fetal growth deceleration in uncomplicated twin pregnancies to an evolutionary adaptive process. Evaluating longitudinal fetal soft-tissue development may provide important insights into differential fetal growth trajectories between twins and singletons.

Objective: To compare twin vs singleton lean and fat tissue growth across pregnancy.

Design, setting, and participants: Prospective cohort study of dichorionic twins and singletons with serial ultrasound scans to chart fetal growth (2009-2013) and collect fetal volume data to measure fat and lean tissue (2015-2019) in 12 US clinical centers. Participants were individuals with singleton (n = 2802 enrolled) and twin (n = …

Anti-Mullerian Hormone (Amh) Protects Ovarian Follicle Loss By Downregulating Granulosa Cell Function In In Vitro And In Vivo Models, Laura Detti, Michael C Mari, Michael P Diamond, Ghassan M Saed

Faculty, Staff and Students Publications

Purpose: AMH inhibits hormone production in luteinized granulosa cells (GCs) and stalls ovarian follicle development in vitro and in vivo. We sought to confirm AMH's mechanism of action through SMAD activation and investigate AMH inhibition of follicle development and function, in vitro and in vivo.

Methods: A primary culture of GCs isolated from follicular fluid was used, and cells were treated with recombinant AMH (rAMH) or placebo for 24 h. For the mouse model, 18-weeks old C57BL female mice were either euthanized at the beginning or treated with rAMH or normal saline for 3 weeks. Primordial (PDF), primary follicle (PRF), …

Interactions Between Adgrf1 (Gpr110) And Extracellular Matrix Proteins Govern Its Effects On Tumorigenesis In Her2-Positive Breast Cancer, Noor Mazin Abdulkareem, Raksha Bhat, Micah Castillo, Sung Yun Jung, Suhas Vasaikar, Sarmistha Nanda, Alexis Ruiz, Martin Shea, Wangjia Cao, Jamunarani Veeraraghavan, Hee-Yong Kim, Tasneem Bawa-Khalfe, Tahir Hussain, Xinli Liu, Preethi Gunaratne, Rachel Schiff, Meghana V Trivedi

Faculty, Staff and Students Publications

Background and purpose: We and others have previously shown that ADGRF1, an adhesion G protein-coupled receptor, is overexpressed and associated with poor survival in many cancers, including human epidermal growth factor receptor-2 (HER2) breast cancer (BC). Also, we have reported the tumour-promoting function of ADGRF1 using preclinical models of HER2+ BC. In this study, we investigated the effect of ADGRF1 overexpression in an orthotopic in vivo model as well as downstream signalling of ADGRF1 in HER2+ BC.

Experimental approach: We utilized a doxycycline (Dox)-induced ADGRF1 overexpression system in HER2+ BC cell lines and performed various in vitro and in vivo …

G-Protein Coupled Receptors In Metabolic Reprogramming And Cancer, Songyeon Ahn, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

G-protein coupled receptors (GPCR) are one of the frequently investigated drug targets. GPCRs are involved in many human pathophysiologies that lead to various disease conditions, such as cancer, diabetes, and obesity. GPCR receptor activates multiple signaling pathways depending on the ligand and tissue type. However, this review will be limited to the GPCR-mediated metabolic modulations and the activation of relevant signaling pathways in cancer therapy. Cancer cells often have reprogrammed cell metabolism to support tumor growth and metastatic plasticity. Many aggressive cancer cells maintain a hybrid metabolic status, using both glycolysis and mitochondrial metabolism for better metabolic plasticity. In addition …

Performance Of Stool-Based Molecular Tests And Processing Methods For Paediatric Tuberculosis Diagnosis: A Systematic Review And Meta-Analysis, Lucía Carratalà-Castro, Shilzia Munguambe, Belén Saavedra-Cervera, Petra De Haas, Alexander Kay, Olivier Marcy, Pamela Nabeta, Willy Ssengooba, Elisabetta Ghimenton-Walters, Sozinho Acácio, Maryline Bonnet, Joanna Ehrlich, Andrew R Dinardo, Anca Vasiliu, Christoph Lange, Sabine Hermans, Anna M Mandalakas, Elisa López-Varela, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase …

Histologic- And Genomic-Directed Adjuvant Therapy For Ampullary Adenocarcinoma: A Hidden Genome-Derived Analysis, Brett L Ecker, Kenneth Seier, Ankur Choubey, Austin M Eckhoff, Gabriella N Tortorello, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Charles M Vollmer, Alice C Wei, Sabino Zani, Australian Pancreatic Genome Initiative, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Background: The benefit of adjuvant chemotherapy (AC) for ampullary adenocarcinoma is unclear. The Hidden Genome model classifies prognostic subtypes with greater accuracy than standard histologic classification (intestinal [INT] vs pancreatobiliary [PB]), but its predictive capacity to guide the use of AC remains unstudied.

Methods: We applied the Hidden Genome model to an international cohort of 183 patients with resected ampullary adenocarcinoma who underwent genomic sequencing. The model quantified the predicted cell of origin (colorectal vs pancreas/distal bile duct) in all specimens. Overall survival (OS) was compared using Kaplan-Meier estimates, stratified by AC use versus surgery alone (SA).

Results: Most patients …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Joint Analysis Of The Npod-Virus Group Data: The Association Of Enterovirus With Type 1 Diabetes Is Supported By Multiple Markers Of Infection In Pancreas Tissue, Sarah J Richardson, Teresa Rodriguez-Calvo, Jutta E Laiho, John S Kaddis, Julius O Nyalwidhe, Irina Kusmartseva, Sofia Morfopoulou, Joseph F Petrosino, Vincent Plagnol, Kathrin Maedler, Margaret A Morris, Jerry L Nadler, Mark A Atkinson, Matthias Von Herrath, Richard E Lloyd, Heikki Hyoty, Noel G Morgan, Alberto Pugliese, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated autoantibodies (AAbs), the latter representing preclinical disease. Two accompanying manuscripts from the nPOD-Virus Group report primary data from a coordinated analysis of multiple enterovirus indices. We aimed to comprehensively assess the association of multiple enterovirus markers with type 1 diabetes.

Methods: The nPOD-Virus …

International Society For Cell & Gene Therapy Expanded Access Working Group Position Paper: Key Considerations To Support Equitable And Ethical Expanded Access To Investigational Cell- And Gene-Based Interventions, Elena Maryamchik, Laertis Ikonomou, Beth E Roxland, Felix Grignon, Bruce L Levine, Bambi J Grilley

Center for Medical Ethics and Health Policy Staff Publications

This position paper reviews the Expanded Access pathway for cell and gene therapies, examining its critical role at the nexus of patient need, regulatory frameworks, and scientific advancement. Spearheaded by the International Society for Cell & Gene Therapy's Expanded Access Working Group, it explores how investigational therapies are accessed outside of clinical trials for patients with serious or life-threatening conditions when no approved alternatives exist. Access to cell and gene therapy products are of specific interest to patients because many times the products are bespoke, being used to treat serious and/or incurable conditions, and are potentially curative. As the field …

Promises And Pitfalls Of Preimplantation Genetic Testing For Polygenic Disorders: A Narrative Review, Jaime A Roura-Monllor, Zachary Walker, Joel M Reynolds, Greysha Rivera-Cruz, Avner Hershlag, Gheona Altarescu, Sigal Klipstein, Stacey Pereira, Gabriel Lázaro-Muñoz, Shai Carmi, Todd Lencz, Ruth Bunker Lathi

Center for Medical Ethics and Health Policy Staff Publications

Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. PGT-P makes use of polygenic risk scores for conditions which are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from about 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent one offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views …

Managing Hypercholesterolemia In Adults Older Than 75 Years Without A History Of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From The National Lipid Association And The American Geriatrics Society, Vera Bittner, Sunny A Linnebur, Dave L Dixon, Daniel E Forman, Ariel R Green, Terry A Jacobson, Ariela R Orkaby, Joseph J Saseen, Salim S Virani

Faculty, Staff and Students Publications

The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL-cholesterol and non-HDL-cholesterol levels remain predictive of incident atherosclerotic cardiovascular events among individuals older than 75 years. Risk prediction among older individuals is less certain because most current risk calculators lack specificity in those older than 75 years and do not adjust for co-morbidities, functional status, frailty, and cognition which significantly impact prognosis in this age group. Data on the benefits and risks of lowering LDL-cholesterol with statins in older patients without atherosclerotic cardiovascular disease are also limited since most primary prevention trials have included mostly younger patients. Available …

A Sumo-Interacting Motif In The Guanine Nucleotide Exchange Factor Epac1 Is Required For Subcellular Targeting And Function, Wenli Yang, Fang Mei, Wei Lin, Jason E Lee, Si Nie, Christopher J Bley, André Hoelz, Xiaodong Cheng

The Brown Foundation: Institute of Molecular Medicine

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO-interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/nucleoporin 358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex. Mutational disruption of EPAC1 SIM interferes with EPAC1's ability to activate its canonical effectors, small GTPases, Rap1 and Rap2, and noncanonical functions, such as the formation …

Middle Meningeal Artery Embolization As A Perioperative Adjunct To Surgical Evacuation Of Nonacute Subdural Hematomas: An Multicenter Analysis Of Safety And Efficacy, Walid K Salah, Cordell Baker, Jonathan P Scoville, Joshua C Hunsaker, Christopher S Ogilvy, Justin M Moore, Howard A Riina, Elad I Levy, Alejandro M Spiotta, Brian T Jankowitz, C Michael Cawley, Alexander A Khalessi, Omar Tanweer, Ricardo Hanel, Bradley A Gross, Okkes Kuybu, Alex Nguyen Hoang, Ammad A Baig, Mir Hojjat Khorasanizadeh, Aldo A Mendez, Gustavo Cortez, Jason M Davies, Sandra Narayanan, Brian M Howard, Michael J Lang, Adnan H Siddiqui, Ajith Thomas, Peter Kan, Jan-Karl Burkhardt, Mohamed M Salem, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

By 2030, nonacute subdural hematomas (NASHs) will likely be the most common cranial neurosurgery pathology. Treatment with surgical evacuation may be necessary, but the recurrence rate after surgery is as high as 30%. Minimally invasive middle meningeal artery embolization (MMAE) during the perioperative period has been posited as an adjunctive treatment to decrease the potential for recurrence after surgical evacuation. We evaluated the safety and efficacy of concurrent MMAE in a multi-institutional cohort.

Methods

Data from 145 patients (median age 73 years) with NASH who underwent surgical evacuation and MMAE in the perioperative period were retrospectively collected from 15 …

Conduction System Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Heart Failure And Mildly Reduced Left Ventricular Ejection Fraction: Results From International Collaborative Lbbap Study (I-Clas) Group, Pugazhendhi Vijayaraman, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit Sharma, Manuel Molina-Lerma, Marek Jastrzębski, Zachary Whinnett, Kevin Vernooy, Rajeev K Pathak, Roderick Tung, Gaurav Upadhyay, Karol Curila, Dipen Zalavadia, Nischay Shah, Lina Marcantoni, Mohamed Gad, Ramez Morcos, Pawel Moskal, Akriti Naraen, Mishal Mumtaz, Jamario R Skeete, Praneet S Katrapati, Jeffrey Kolominsky, Johan Van Koll, Mihail G Chelu, Kenneth A Ellenbogen, Oscar Cano

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) is a guideline-recommended therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF, 36%-50%) and left bundle branch block or indication for ventricular pacing. Conduction system pacing (CSP) using left bundle branch area pacing or His bundle pacing has been shown to be a safe and physiologic alternative to biventricular pacing (BVP).

Objective: The aim of this study was to compare the clinical outcomes between BVP and CSP for patients with HFmrEF undergoing CRT.

Methods: Consecutive patients who underwent BVP or CSP with HFmrEF between January 2018 and June 2023 at 16 international …

Polyclonal Plasma Cell (Polypc) Signature As A Key Indicator For Predicting The Progression Of Mgus To Multiple Myeloma, Fumou Sun, Yan Cheng, Catherine Ma, Hongwei Xu, Clyde Bailey, David Mery, Timothy Cody Ashby, Daisy Alapat, Yong Li, Ken H Young, Samer Al Hadidi, Sharmilan Thanendrarajan, Carolina Schinke, Maurizio Zangari, Frits Van Rhee, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Students Publications

Background

Multiple myeloma (MM) is virtually always preceded by monoclonal gammopathy of undetermined significance (MGUS). Elevated serum markers are used to classify MGUS patients into clinical risk categories. Previous research has indicated that the absence of a normal plasma cell signature in MGUS is linked to early progression.

Objective

To confirm that the presence of a “polyclonal plasma cell (PolyPC) signature” serves as a robust negative predictor of MGUS progression.

Methods

374 MGUS patients were enrolled, including 334 patients with stable disease and 40 patients who progressed to MM within 10 years. An oligonucleotide microarray analysis was performed on mRNA …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Hiroko Yano, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

METHODS: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

RESULTS: NF2 loss-of-function (LOF) …

Age-Related Mesenchymal Stromal Cell Senescence Is Associated With Progression From Mgus To Multiple Myeloma, Natalya Plakhova, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) increases with advancing age, suggesting that progression may be influenced by age-related changes within the bone marrow (BM) microenvironment. We hypothesise that senescent mesenchymal stromal cells (MSCs), which accumulate in the BM with age, may contribute to MGUS progression to MM. Here, we show that, like BM MSCs from aged non-cancer controls, BM MSCs from both MM and MGUS patients exhibit a senescent phenotype characterised by enlarged, flattened morphology, increased β-galactosidase activity and CDKN2A expression, and decreased proliferation rate compared with BM MSCs from healthy …

Assessing Neurocognitive Maturation In Early Adolescence Based On Baby And Adult Functional Brain Landscapes, Omid Kardan, Muriah D Wheelock, Jiaxin Cindy Tu, Et Al.

2020-Current year OA Pubs

Adolescence is a period of growth in cognitive performance and functioning. Recently, data-driven measures of brain-age gap, which can index cognitive decline in older populations, have been utilized in adolescent data with mixed findings. Instead of using a data-driven approach, here we assess the maturation status of the brain functional landscape in early adolescence by directly comparing an individual's resting-state functional connectivity (rsFC) to the canonical early-life and adulthood communities. Specifically, we hypothesized that the degree to which a youth's connectome is better captured by adult networks compared to infant/toddler networks is predictive of their cognitive development. To test this …

Measuring And Interpreting Individual Differences In Fetal, Infant, And Toddler Neurodevelopment, Halie A Olson, M Catalina Camacho, Natasha Marrus, Et Al.

2020-Current year OA Pubs

As scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a "standard" way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying "development" influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research …

A Subset Of Cortical Areas Exhibit Adult-Like Functional Network Patterns In Early Childhood, Jiaxin Cindy Tu, Xintian Wang, Donna Dierker, Chloe M. Sobolewski, Evan M Gordon, Timothy O Laumann, Adam T Eggebrecht, Muriah D. Wheelock, Et Al.

2020-Current year OA Pubs

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized into functional networks. These networks show stronger internal and weaker external functional connectivity (FC), with FC profiles more similar within the same network. Previous studies have shown these networks develop from nascent forms before birth to their mature, adult-like structures in childhood. However, these analyses often rely on adult functional network definitions. This study assesses the potential misidentification of infant functional networks when using adult models and explores the consequences and possible solutions to this problem. Our findings suggest that although adult …

Innovations In Intestinal Organoid Technology Featuring An Open Apical Surface, Ye Chen, Yi Wang

2020-Current year OA Pubs

Since the development of the three-dimensional (3D) "mini-gut" culture system, adult stem cell-derived organoid technology has rapidly advanced, providing in vitro models that replicate key cellular, molecular, and physiological properties of multiple organs. The 3D intestinal organoid system has resolved many long-standing challenges associated with immortalized or cancer cell cultures, offering unparalleled capabilities for modeling gastrointestinal development and diseases. However, significant limitations remain, including restricted accessibility to the epithelial apical surface for studying host-microbe interactions, interruptions in modeling chronic gastrointestinal diseases due to frequent passaging and dissociation, and the absence of mechanical cues such as peristalsis and luminal flow, which …

Role Of The Ctcf Binding Site In Human T-Cell Leukemia Virus-1 Pathogenesis, Ancy Joseph, Xiaogang Cheng, John Harding, Jacob Al-Saleem, Patrick Green, Malachi Griffith, Deborah Veis, Daniel A. Rauch, Lee Ratner

2020-Current year OA Pubs

During HTLV-1 infection, the virus integrates into the host cell genome as a provirus with a single CCCTC binding protein (CTCF) binding site (vCTCF-BS), which acts as an insulator between transcriptionally active and inactive regions. Previous studies have shown that the vCTCF-BS is important for maintenance of chromatin structure, regulation of viral expression, and DNA and histone methylation. Here, we show that the vCTCF-BS also regulates viral infection and pathogenesis in vivo in a humanized (Hu) mouse model of adult T-cell leukemia/lymphoma. Three cell lines were used to initiate infection of the Hu-mice, i) HTLV-1-WT which carries an intact HTLV-1 …

The Medial Antebrachial Cutaneous Nerve Is A Low-Morbidity Alternative To The Standard Sural Nerve Autograft, Stahs Pripotnev, Sai L Pinni, Suzanne Zhou, Gary Skolnick, Susan E Mackinnon

2020-Current year OA Pubs

BACKGROUND: Nerve interposition grafting is an important technique in nerve reconstructive surgery that is used when a primary repair is not feasible without significant tension. This study sought to evaluate the long-term morbidity of the medial antebrachial cutaneous (MABC) nerve as an alternative donor nerve in comparison with sural nerve harvest.

METHODS: A single surgeon and institution retrospective chart review was performed to identify all patients who underwent nerve autografting using the sural and MABC as donor nerves between January 1, 2000 and December 31, 2019. Surveys assessed overall patient satisfaction with surgery, as well as donor and recipient site …

Compression Of The Ulnar Nerve By The Arcade Of Struthers: Look And You Shall Find, Shady Elmaraghi, Ruby Taylor, Isaac Tung, Megan M Patterson, Susan E Mackinnon

2020-Current year OA Pubs

BACKGROUND: The arcade of Struthers was first proposed by Kane et al in 1973. Clinical investigations of this structure have been limited to small case series, focusing on the arcade as an isolated cause of compressive ulnar neuropathy. The purpose of our study was to investigate the incidence of this structure in patients undergoing ulnar nerve transposition.

METHODS: A retrospective chart review of prospectively maintained data in a single surgeon's practice was performed. Records of patients undergoing surgery for compressive ulnar neuropathy at the cubital tunnel were evaluated for documentation of a compressive arcade of Struthers. In addition, a scoping …

Large-Scale Network Analysis Of The Cerebrospinal Fluid Proteome Identifies Molecular Signatures Of Frontotemporal Lobar Degeneration, Rowan Saloner, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic …