Digital Commons Network^™

Twenty-Five Years Of Palivizumab: A Global Historic Review Of Its Impact On The Burden Of Respiratory Syncytial Virus Disease In Children, Xavier Carbonell-Estrany, Eric A F Simões, Louis Bont, Paolo Manzoni, Heather J Zar, Anne Greenough, Octavio Ramilo, Renato Stein, Barbara Law, Asuncion Mejias, Manuel Sanchez Luna, Paul A Checchia, Leonard Krilov, Marcello Lanari, Ron Dagan, Brigitte Fauroux, Bernhard Resch, Terho Heikkinen, Joseph B Domachowske, Joanne G Wildenbeest, Federico Martinon-Torres, Richard Thwaites, Merih Cetinkaya, Adel S Alharbi, Carlos E Rodriguez-Martinez, Daniel E Noyola, Asiah Kassim, Satoshi Kusuda, Ji-Man Kang, Barry Rodgers-Gray, Anna Platonova, Fungwe Jah, Bosco Paes

Faculty, Staff and Students Publications

Introduction: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in young children. For 25 years, palivizumab has been the only effective pharmaceutical RSV preventive.

Areas covered: We summarize the development and a quarter-century of real-world evidence with palivizumab. We highlight its positive impact on the burden of RSV in high-risk children. Based on lessons learnt from its implementation, we suggest strategies for effective and equitable deployment of newer RSV preventives.

Expert opinion: Following failure of the formalin-inactivated RSV vaccine in 1967, RSV intravenous immunoglobulin was approved in 1996 after three decades' research. Subsequently, palivizumab emerged as the most effective …

Functional Mobility And Pain Are Improved For 6 Years After Adolescent Bariatric Surgery, Neil Thivalapill, Todd M Jenkins, Thomas H Inge, Changchun Xie, Anita P Courcoulas, Carroll M Harmon, Michael A Helmrath, Stephanie Sisley, Marc P Michalsky, Justin R Ryder, Teen‐Longitudinal Assessment Of Bariatric Surgery (Teen‐Labs) Consortium

Faculty, Staff and Students Publications

Objective: The long-term durability of improvements in functional mobility and musculoskeletal pain for adolescents after metabolic and bariatric surgery (MBS) is unknown.

Methods: We used the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study to determine the change in mobility and pain among adolescents who underwent MBS. From standardized 400-m walk tests, we analyzed walk time, heart rate (HR) parameters, and musculoskeletal pain.

Results: The mean walk time improved from 383 s (95% CI: 368-399) prior to surgery to 351 s (95% CI: 330-372) by 6 years. The mean resting HR was 90 beats per minute (bpm; 95% CI: 87-93) preoperatively …

Severe Gastrointestinal Manifestations In Childhood-Onset Lupus: A Single-Center Cohort And Review Of The Literature, James Orozco, Jessica Nguyen, Sara Mm Yasrebi, Marnie Blalock, Sara L Grisales, Craig L Jensen, Marietta M Deguzman

Faculty, Staff and Students Publications

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune condition with diverse manifestations. Childhood-onset SLE (cSLE) presents more severely than adult-onset disease with a higher incidence of severe neurologic or renal manifestations and lower estimated survival rates. There is limited literature on the range of severe gastrointestinal manifestations at presentation in cSLE, and this lack of information results in underappreciation of these potentially life-threatening complications and little guidance regarding management of these patients.

Methods

We reviewed cases of patients with cSLE and severe GI manifestations at presentation diagnosed at our institution and additionally provide a comprehensive review of existing cases …

Are Education, Socioeconomic Status, And Household Size Dependent Variables Influencing The Developmental Origins Of Inflammatory Bowel Disease?, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

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 …

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 …

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 …

All Genetic Subtypes Of B-Cell Acute Lymphoblastic Leukemia Exhibit Increased Incidence Rates In Children With Down Syndrome, Ching-Ju Hsu, Jeremy M Schraw, Tania A Desrosiers, Amanda E Janitz, Russell S Kirby, Eirini Nestoridi, Wendy N Nembhard, Jason L Salemi, Charles Shumate, Jean Paul Tanner, Mahsa M Yazdy, Michael E Scheurer, Karen R Rabin, Philip J Lupo

Faculty, Staff and Students Publications

No abstract provided.

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 …

Characteristic Profiling Of Cho-Cell Expressed Mers-Cov Rbd-Fc, Mashal M Almutairi, Yi-Lin Chen, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Wen-Hsiang Chen

Faculty, Staff and Students Publications

The ongoing circulation of the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in camels across Asia, the Middle East, and Africa, along with its occasional transmission to humans, demonstrates a need for a MERS vaccine. Previously, we have reported a receptor binding domain (RBD) of MERS-CoV fused with human Fc as a promising vaccine antigen (MERS-CoV RBD-Fc). We generated a stable recombinant CHO cell line expressing such a protein and developed a basic production process suitable for future technological transfer to pilot-scale manufacture. In this study, we employed various in-house analytical assays to examine the characteristics of purified RBD-Fc protein and …

Dosing Recommendations For Ampicillin And Ceftriaxone In The Treatment Of Pediatric Community-Acquired Pneumonia Using Monte Carlo- And Physiologic-Based Pharmacokinetic Simulations, Norint Tung, Dustin Huynh, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Tyler H Do, Amartya Setty, Lana Hoang, John S Bradley, Jennifer Le

Faculty, Staff and Students Publications

Objective: Since 2011, Ampicillin (AMP) has been recommended as the parenteral antibiotic of choice for pediatric community-acquired pneumonia (CAP), but ceftriaxone (CRO) is recommended for unvaccinated children and those with complicated CAP. Using penicillin and CRO susceptibility data for pneumococcus, we evaluated the adequacy of currently recommended doses of AMP and CRO.

Methods: With nonlinear mixed-effects modeling v7.3, Monte Carlo simulations (MCS, N = 10,000) for AMP and CRO were conducted for 6 virtual patients aged 3 months, 1, 2, 5, 10, and 15 years. PK-Sim v9.0 was used to develop physiologic-based pharmacokinetic (PBPK) models for AMP (N = 4000) …

Neuroanatomical Features Of Naa10 And Naa15-Related Neurodevelopmental Syndromes, Rahi Patel, Rikhil Makwana, Carolina Christ, Elaine Marchi, Christina Y Miyake, Fabricio Guimaraes Goncalves, Gholson J Lyon, Matthew T Whitehead

Faculty, Staff and Students Publications

Background: NAA10-related and NAA15-related neurodevelopmental (ND) syndromes present with intellectual disability, hypotonia, cardiac abnormalities, and delayed development. While data exists on the clinical manifestations of these conditions, there are few reports describing the neuroanatomical abnormalities present on imaging.

Objective: We aim to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess the severity and number of neuroanatomical anomalies and their associated functional impairments to better understand the pathophysiology of these disease processes.

Materials and methods: Neuroimaging studies were obtained from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in …

"Touch&Play" Wood Typification By The Masspec Pen, Adriano Reis, Caroline Pais Carvalho, Iasmim Lopes De Lima, Felipe R P Mansoldo, Alane Beatriz Vermelho, Rosineide Costa Simas, Livia S Eberlin, Marcos N Eberlin

Faculty, Staff and Students Publications

We have investigated the ability of a MasSpec Pen (MSPen) "three-in-one" (extraction, transfer, and ionization) device coupled to a mass spectrometer to provide instantaneous chemical profiles that could promptly characterize wood samples from the mahogany (Meliaceae) family. For that, we selected a set of five representative wood species, that is, Brazilian mahogany (Swietenia macrophylla, also known as Honduran mahogany), two African mahoganies (Khaya ivorensis and Khaya senegalensis), and two "nongenuine" ("fake") mahogany woods: cedar (Cedrela odorata) and andiroba (Carapa guianensis). By simply touching the superficially polished wood surface and after 3 s of automatic extraction, profiles of highly characteristic markers …

Biomolecular Condensates In Immune Cell Fate, Srikanth Kodali, Caroline M Sands, Lei Guo, Yun Huang, Bruno Di Stefano

Faculty, Staff and Students Publications

Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory proteins. Findings have established a link between condensate formation and the gene regulatory networks that ensure the proper development of immune cells. Conversely, condensate dysregulation has been linked to impaired immune cell fates, including ageing and malignant transformation. This Review …

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 …

Stress, Employment Changes, And Psychological Distress Among Caregivers Of Patients With Head And Neck Cancer, Lama Abdurrahman, Vlad C Sandulache, Cielito Reyes-Gibby, Erich M Sturgis, Pavan Jhaveri, Hoda Badr

Faculty, Staff and Students Publications

Importance: Patients undergoing external beam radiation therapy (EBRT) for head and neck cancer (HNC) often experience adverse effects that require substantial caregiving. The burdens of caregiving can impact caregiver employment and mental health over time, yet this topic remains underexplored.

Objective: To examine the associations between caregiving for patients with HNC who undergo EBRT and caregiver stress, employment status, and psychological distress.

Design, setting, and participants: This was a secondary analysis of data from a longitudinal survey study that surveyed caregivers at baseline (ie, at initiation of EBRT) and at 4-month and 12-month follow-ups. The study was conducted at 2 …

The Aging Ovary Stands On The Shoulders Of Giant Multinucleated Cells, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

Reproductive aging is associated with declining fertility and increasing inflammation, though these events are not well understood. An exciting new study in PLOS Biology utilizes cutting-edge technologies to characterize the role of multinucleated giant cells in ovarian aging.

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 …

Is Less More? Maximizing Outcomes By Tailoring Treatments To Patients: Oncofertility And Oncomenopause, Janice S Kwon, Marie Plante, Martha Hickey, Annabelle Huguenin, Sarah Hmaidan, Terri Lynn Woodard

Faculty, Staff and Students Publications

Notable advances have been made in improving survival outcomes in various cancers, but some have incurred undesirable costs and effects to patients with respect to fertility and menopause. Patients are living longer with cancer, and patient reported outcomes are influencing decision-making by individuals and their health care providers. It is essential to evaluate existing standards of care on an ongoing basis and prioritize quality of life and long-term survivorship, particularly for interventions in early-stage cancers and risk-reducing strategies that often yield long-term life expectancy.

Point-Of-Care Ultrasound For Guiding Pulmonary Artery Catheter Placement, Erik Su, Saul Flores

Faculty, Staff and Students Publications

No abstract provided.

A Phenotypic Screen Identifies Xanthohumol And Other Flavonoids As Killers Of Bladder Cancer, Michael J Bolt, Jessica Oceguera, Alejandra Rivera Tostado, Christopher D Candler, Elina Mosa, Kazem Safari, Maureen G Mancini, Michael A Mancini

Faculty, Staff and Students Publications

Bladder cancer accounts for 4 % of cancer diagnoses in the US. Current treatments primarily involve trans-urethral resection of bladder tumors (TURBT) and immunotherapy with Bacille Calmette-Guerin (BCG). Despite the efficacy of TURBT, issues with residual tumors persist. We chose to utilize Cell Painting to screen a set of 244 flavonoid compounds for bladder cancer cell toxicity. Using multiparametric high content analysis termed SPACe, we discover promising candidates underscoring the potential of flavonoids in targeting bladder cancer cells and elucidating their mechanisms of action. Notably, compounds such as xanthohumol show promise in reducing cancer cell viability by altering lipid metabolism. …

Graphage: Unleashing The Power Of Graph Neural Network To Decode Epigenetic Aging, Saleh Sakib Ahmed, Nahian Shabab, Abul Hassan Samee, M Sohel Rahman

Faculty, Staff and Students Publications

DNA methylation is a crucial epigenetic marker used in various clocks to predict epigenetic age. However, many existing clocks fail to account for crucial information about CpG sites and their interrelationships, such as co-methylation patterns. We present a novel approach to represent methylation data as a graph, using methylation values and relevant information about CpG sites as nodes, and relationships like co-methylation, same gene, and same chromosome as edges. We then use a graph neural network (GNN) to predict age. Thus our model, GraphAge leverages both the structural and positional information for prediction as well as better interpretation. Although, we …

An Electronic, Preclinic, Social Determinants Survey Shows Pediatric Atherosclerotic Risk Factor Referral Identifies At-Risk Families, Justin R Rahman, Bethany S Zachariah, Christina Y Miyake, Deidra Ansah, Justin P Zachariah

Faculty, Staff and Students Publications

Objective: Atherosclerotic risk factors are prevalent in childhood. Risk factors are associated with social determinants of health (SDoH), but have never been demonstrated in a clinical pediatric cardiology cohort. This report details the first use of a remotely deployed, previsit, self-administered electronic survey for the ascertainment of SDoH in youth referred to pediatric cardiology. We hypothesized that patients referred for atherosclerotic risk factors would have higher risk of SDoH factors.

Study design: SDoH were assessed using validated instruments from the PRAPARE toolkit and the Accountable Health Communities Health-Related Social Needs Screening Tool automatically deployed days before a scheduled visit in …

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 …

Rna Interference In Protozoan Parasites And Its Application, Lon-Fye Lye, Deborah E Dobson, Stephen M Beverley, Min-Che Tung

2020-Current year OA Pubs

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression, via small RNA triggers derived from double-stranded RNA that can target specific genes; it is a natural process that plays a role in both the regulation of protein synthesis and in immunity. Discovery of RNAi by Fire and Mello in 1998 had a profound impact on unraveling novel aspects of eukaryotic biology. RNA interference (RNAi) has proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms. A great advance in …

Claustrum Volume Is Reduced In Multiple Sclerosis And Predicts Disability, Nicole Shelley, Bradley Judge, Dmitriy A Yablonskiy, Robert T Naismith, Matthew R Brier, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS).

METHODS: This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation.

RESULTS: …

Screpertoire 2: Enhanced And Efficient Toolkit For Single-Cell Immune Profiling, Qile Yang, Ksenia R. Safina, Kieu Diem Quynh Nguyen, Zewen Kelvin Tuong, Nicholas Borcherding

2020-Current year OA Pubs

Single-cell adaptive immune receptor repertoire sequencing (scAIRR-seq) and single-cell RNA sequencing (scRNA-seq) provide a transformative approach to profiling immune responses at unprecedented resolution across diverse pathophysiologic contexts. This work presents scRepertoire 2, a substantial update to our R package for analyzing and visualizing single-cell immune receptor data. This new version introduces an array of features designed to enhance both the depth and breadth of immune receptor analysis, including improved workflows for clonotype tracking, repertoire diversity metrics, and novel visualization modules that facilitate longitudinal and comparative studies. Additionally, scRepertoire 2 offers seamless integration with contemporary single-cell analysis frameworks like Seurat and …

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) …

Biological Age Acceleration Associated With The Progression Trajectory Of Cardio-Renal–Metabolic Multimorbidity: A Prospective Cohort Study, Yixing Tian, Jinqi Wang, Tianyu Zhu, Xia Li, Haiping Zhang, Xiaoyu Zhao, Xinghua Yang, Yanxia Luo, Lixin Tao, Zhiyuan Wu, Xiuhua Guo

Research outputs 2022 to 2026

Objectives: Previous studies have confirmed that biological age (BA) acceleration is associated with single cardio-renal–metabolic diseases (CRMDs), typically including type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease. However, its association with progression to cardio-renal–metabolic multimorbidity (CRMM, coexistence of ≥2 CRMDs) and subsequent mortality remains unexplored. Methods: Using the multi-state model, we analyzed 278,927 UK Biobank participants free of CRMDs at baseline to investigate the association between BA acceleration—measured by phenotypic age (PhenoAge) and Klemera–Doubal method age (KDMAge)—and CRMM progression trajectory, from health to the first CRMD and then to CRMM and death. BA acceleration was the residual from …