Digital Commons Network^™

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Social Anxiety, Negative Affect, And Hearing Difficulties In Adults, Katrina Kate S. Mcclannahan, Sarah Mcconkey, Julia M Levitan, Thomas L Rodebaugh, Jonathan E Peelle

2020-Current year OA Pubs

Subjective ratings of communication function reflect both auditory sensitivity and the situational, social, and emotional consequences of communication difficulties. Listeners interact with people and their environment differently, have various ways of handling stressful situations, and have diverse communication needs. Therefore, understanding the relationship between auditory and mental health factors is crucial for the holistic diagnosis and treatment of communication difficulty, particularly as mental health and communication function may have bidirectional effects. The goal of this study was to evaluate the degree to which social anxiety and negative affect (encompassing generalized anxiety, depression, and anger) contributed to subjective communication function (hearing …

Location And Extent Of Disease Predicts Outcome Of Neurofibromatosis Type 1-Related Pediatric Low-Grade Gliomas, Sneha M Chaturvedi, Arohi Saxena, Ahmad Hassan, Ali Mian, Chelsea Kotch, Nicole M Brossier

2020-Current year OA Pubs

No abstract provided.

Qualitative And Quantitative Analysis Of A Novel Dental Health Education Program To Improve Dental Care Utilization By Bhutanese-, Burmese-, And Swahili-Speaking Refugees In A Midwestern United States City, Chandra Swanson, Katherine Gordon, Kelly Kreisler, Elizabeth Montgomery Collins

2020-Current year OA Pubs

No abstract provided.

Enhancing Safety: Multi-Institutional Fmea And Fta On 177 Lu-Based Radio-Pharmaceutical Therapy, Siju C George, Santiago Aguirre, Nichole M Maughan, Ranjini Tolakanahalli, E James Jebaseelan Samuel, Sven L Gallo, Jacqueline E Zoberi, Yongsook C Lee

2020-Current year OA Pubs

PURPOSE: This study investigates potential failure modes and conducts failure mode and effects analysis (FMEA) and fault tree analysis (FTA) on the administration of

METHODS: We reviewed the literature to investigate the administration of Pluvicto and Lutathera, focusing on prospective procedural failures and potential failure modes (PFMs) and their outcomes. We distributed an FMEA survey to multiple experienced centers in

RESULTS: The findings from the literature review and survey responses on the prospective study have identified several critical areas at risk of failure. These areas include non-optimized treatment delivery, inadequate patient monitoring, and lack of safety training, leading to radiation …

Integrating Mapk Pathway Inhibition Into Standard-Of-Care Therapy For Pediatric Low-Grade Glioma, Erin E Crotty, Aimee A Sato, Mohamed S Abdelbaki

2020-Current year OA Pubs

Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of

Multidisciplinary Approach To Treating Complex Immune Dysregulation Disorders: An Adaptive Model For Institutional Implementation, Lauren A Henderson, Megan A Cooper, Anthony French, Et Al.

2020-Current year OA Pubs

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]). However, published information on the composition and function of immMDTs is sparse, and there is little guidance for those seeking to establish or optimize an immMDT. To inform this review, we assembled a panel of …

Mapping Of Rorγt+ Dendritic Cells In Human Tissues Establishes Their Preferential Niche In Adult Lymph Nodes, Silvia Lonardi, Shitong Wu, Alina Ulezko Antonova, Yizhou A Liu, Marina Cella, Marco Colonna, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: The retinoic-acid-receptor-related orphan receptor gamma t (RORγt) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express RORγt. This study maps the presence of RORγt cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.

METHODS: By combining multicolor flow cytometry, RNAseq of peripheral blood cells, analysis of lymph node scRNAseq datasets, and microscopic analysis on human tissue sections and single-cell suspensions, this study maps the presence of RORγt cells …

Anticodon-Edited Trna Enables Translational Readthrough Of Col4a5 Premature Termination Codons, Kohei Omachi, Joseph J. Porter, John D. Lueck, Jeffrey H. Miner

2020-Current year OA Pubs

Alport syndrome is caused by variants in COL4A3, COL4A4, or COL4A5, which encode the α3α4α5 chains of type IV collagen. These variants result in defects in the glomerular basement membrane (GBM) and impaired kidney function. Nonsense variants result in truncated proteins lacking the NC1 domain, thereby preventing proper GBM assembly and function and causing the most severe forms of the disease. Restoring full-length protein expression represents a potential therapeutic strategy for Alport syndrome and related disorders. Anticodon-edited transfer RNAs (ACE-tRNAs), which promote premature termination codon (PTC) readthrough, have shown promise in diseases such as cystic fibrosis, but their application in …

Comparative Effectiveness Of Epilepsy Surgery Versus Additional Anti-Seizure Medications For Lennox-Gastaut Syndrome: Study Protocol For A Multicenter, Mixed-Methods Study, Sandi Lam, Liu Lin Thio, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Lennox-Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy without a known cure. Management of symptoms requires substantial care. Treatment options include anti-seizure medications, dietary therapy, and epilepsy surgery. Two main treatment pathways for patients with LGS with drug resistant epilepsy are additional anti-seizure medications or epilepsy surgery, which have been reported to be effective in reduction of seizure burden and improving quality of life. No studies have directly compared the outcomes of using epilepsy surgery versus using additional anti-seizure medications for the treatment of LGS.

METHODS: This study is a multicenter, mixed-methods comparative effectiveness study of LGS patients …

The Perfect Storm: Unraveling The Interplay Of Genetic Predisposition And Viral Triggers In Type 1 Diabetes Pathogenesis, Daniel A Veronese-Paniagua, Jeffrey R Millman

2020-Current year OA Pubs

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the T cell-mediated destruction of insulin-secreting pancreatic β cells, leaving patients reliant on exogenous insulin to establish normoglycemia. Despite advancements in glucose management, the precise pathological mechanisms linking genetic predisposition and environmental triggers to the loss of immune tolerance remain incompletely understood, hindering the development of preventative therapies. This comprehensive review synthesizes clinical, experimental, and epidemiological data to detail the intricate pathogenesis of T1D, focusing on the convergence of autoimmunity, high-risk genetics, and enteroviral infection. We discuss how T1D is fundamentally a disease caused by failures in central and …

Parp Inhibitors In Melanoma Treatment: Potential, Challenges, And Future Directions, Angela Anaeme, Karen Moussa, Abdallah N Mansour, George Nassief, George Ansstas

2020-Current year OA Pubs

Genome integrity is a critical driver of cellular stability, and defects in the processes that maintain genome health are potent sources of cancer progression. Homologous recombination deficiency (HRD), which damages cells through absent or erroneous repair of double-stranded DNA breaks, is a prime example of such cellular dysfunction. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit these aberrancies in the cellular repair process by arresting the ability of the PARP enzyme to repair cellular and genetic damage, inducing the accumulation of DNA damage and cancer cell death. While the utility of PARP inhibitors has been established in many HRD-associated tumors - particularly breast, …

Molecular Chaperones At The Host-Virus Interface: Heat Shock Protein Roles In Hiv-1 And Emerging Insights For Hiv-2 And Dual Infection, Sabastine Eugene Arthur, Kirk Klogo, Emmanuel Kobina Mensah, Maame Ama Pentsiwa Cudjoe, Adomia Baaba Mensah, Nyamekye Amoabeng Ankrah, Catherine Laaripuoh Omosule, Evelyn Yayra Bonney, George Boateng Kyei

2020-Current year OA Pubs

Heat shock proteins (HSPs) are essential molecular chaperones involved in protein folding, cellular stress responses, and homeostasis. Recent studies reveal their critical and dual roles in the human immunodeficiency virus (HIV) life cycle, both promoting and restricting viral replication, latency, and immune modulation. This review synthesizes current evidence on how key HSP families, HSP70, HSP90, and HSP40, interact with HIV proteins such as Tat, Rev, Nef, and Vpx, affecting viral transcription, protein trafficking, and latency. We also highlight Heat Shock Factor 1 (HSF1) as a direct regulator of the HIV-1 long terminal repeat (LTR), facilitating latency reversal via recruitment of …

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Depression And Weight Loss Trajectories During An Integrated Behavioral Intervention: Within-Treatment Analysis Of The Rainbow Trial, Bailey W. Osweiler, Daphne Lew, Nan Lv, Jun Ma, Thomas G. Kannampallil

2020-Current year OA Pubs

INTRODUCTION: Depression and obesity are two of the most common chronic conditions among US adults. The Research Aimed at Improving Both Mood and Weight (RAINBOW) study was the first randomized clinical trial to demonstrate the effectiveness of an integrated behavioral treatment for depression and obesity. We aimed to characterize the trajectories of both depression symptoms and weight loss during the RAINBOW intervention.

METHODS: Participants (N = 201) randomly assigned to the RAINBOW treatment arm who provided serial data on depression symptoms (via the 9-item Patient Health Questionnaire [PHQ9]) and self-measured weight were included. Group-Based Multi-Trajectory Modeling is a statistical technique …

Diagnosis And Management Of Gastroesophageal Reflux Disease: Current Insights, Abhinav Vayal-Veettil, C Prakash Gyawali

2020-Current year OA Pubs

Gastroesophageal reflux disease (GERD) results from retrograde movement of gastric content into the esophagus and beyond, resulting in symptoms, mucosal injury and long-term complications. Typical symptoms of heartburn and regurgitation are highly suggestive of GERD, but atypical presentations require careful evaluation to rule out alternative diagnoses. Diagnostic modalities, including endoscopy, ambulatory reflux monitoring, and high-resolution manometry, play a pivotal role in confirming GERD and guiding personalized treatment. Management strategies consist of lifestyle modifications, pharmacologic therapy with anti-secretory agents, and adjunctive treatments such as alginates and baclofen. For refractory cases, surgical and endoscopic interventions offer durable symptom relief. Complications of GERD …

Association Of Item-Level Responses To Cognitive Function Index With Tau Pathology And Hippocampal Volume In The A4 Study, Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.

METHODS: In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau

RESULTS: Higher tau

DISCUSSION: These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.

HIGHLIGHTS: Higher …

Accuracy And Reliability Of Video-Based Range-Of-Motion Assessments In Postreconstruction Brachial Plexus Patients, Christopher J. Dy, Stephen J. Demartini, Eshan Sane, David M. Brogan, Planet Study Group

2020-Current year OA Pubs

PURPOSE: Following surgical reconstructions considered successful, many patients with brachial plexus injuries (BPI) have limited limb motion. In addition to manual muscle testing, clinicians typically measure active range of motion (AROM). AROM measurement relies on in-person examination and manual goniometers or visual estimation, both of which are subject to interobserver variability. The purpose of this proof-of-concept study was to evaluate reliability of video-based AROM assessments. We hypothesized that video-based assessment of AROM would have high inter-rater reliability (IRR) among surgeons who perform BPI reconstruction.

METHODS: We video recorded a standardized examination in a convenience sample of 8 postreconstruction BPI patients …

Articles That May Change Your Practice: Reviewing Intraosseous Or Intravenous? Reviewing Intraosseous Versus Intravenous First Approach To Access In Out-Of-Hospital Cardiac Arrest Data From Randomized Controlled Trials, Blaise Loughman, Fatou Ndaw, Aaron J Lacy, James L Li

2020-Current year OA Pubs

No abstract provided.

Surgeons, Physiatrists And Neurologists Speaking "Edx And Nerve Surgery": A Paradigm Shift For Nerve Injured Patients, Deng Pan, Aneri U Patel, J Megan Patterson, Anna Rose Johnson, Travis Gordon, Susan E Mackinnon

2020-Current year OA Pubs

Surgeons' ability to interpret electrodiagnostic (EDX) studies has greatly enhanced patient selection and outcome for nerve surgeries as it has informed our understanding of the classification of nerve injury. EDX measures axons present, lost, or demyelinated. It does not measure an area where axons experience chronic ischemia, making a Sunderland Zero nerve injury a clinical diagnosis that should be suspected when patients have normal EDX, decreased recruitment on electromyography (EMG), and no atrophy. Only observation of recovery in the earliest postoperative period would confirm a Sunderland Zero. In this article, we present an expanded classification of nerve injury, highlighting Sunderland …

De Novo Lipid Synthesis In Cardiovascular Tissue And Disease, Tariq J Khan, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is de novo lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and in vivo genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in …

Abdominal Myosteatosis Measured With Computed Tomography Predicts Poor Outcomes In Patients With Glioblastoma, Farzaneh Rahmani, David H Ballard, Tammie L S Benzinger, Sonika Dahiya, John Evans, Sara Hosseinzadeh Kassani, Cyrus A Raji, Marilyn J Siegel, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).

METHODS: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and …

Evolution And Recent Radiation Therapy Advancement In Uganda: A Precedent On How To Increase Access To Quality Radiotherapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Solomon Kibudde, Daniel Kanyike, Joseph Kigula-Mugambe, Tianyu Zhao, Hiram Gay, Baozhou Sun, Jackson Orem

2020-Current year OA Pubs

The evolution of radiation therapy in Uganda has been a journey marked by significant milestones and persistent challenges. Since the inception of radiotherapy services in 1988-1989, there has been a concerted effort to enhance cancer treatment services. The early years were characterized by foundational developments, such as the installation of the first teletherapy units, low-dose-rate brachytherapy units, and conventional simulators, and the recognition of radiation oncologists and medical physicist professionals laid the groundwork for radiotherapy treatment modalities. With more support from the International Atomic Energy Agency, the acquisition of dosimetry equipment, treatment planning systems, and additional professional training signaled a …

An Explainable Ai Approach For Mapping Multivariate Regional Brain Age And Clinical Severity Patterns In Alzheimer's Disease, Gauri Darekar, Taslim Murad, Hui-Yuan Miao, Deepa S Thakuri, Alzheimer’S Disease Neuroimaging Initiative, Ganesh B Chand

2020-Current year OA Pubs

Age is a significant risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD) and identifying brain age patterns is critical for comprehending the normal aging and MCI/AD processes. Prior studies have widely established the univariate relationships between brain regions and age, while multivariate associations remain largely unexplored. Herein, various artificial intelligence (AI) models were used to perform brain age prediction using an MRI dataset (

Measuring Stigma In Pediatric Oncology: A Cross-Sectional Analysis Of Three Global Sites, Lara E Counts, Sara M Malone, Et Al.

2020-Current year OA Pubs

PURPOSE: Stigma contributes to fear and shame, resulting in delays in care-seeking behavior among individuals with cancer. As a social construct, stigma is affected by language, religion, culture, and local norms. This study explored pediatric cancer stigma at the time of diagnosis across diverse settings through the adaptation of two stigma measures.

METHODS: This study was conducted with adolescents and caregivers of children with osteosarcoma and retinoblastoma at three centers in Jordan, Guatemala, and Zimbabwe. The Stigma-related Social Problems (SSP) and the eight-item Stigma Scale for Chronic Illness (SSCI-8) measures were translated into Arabic, Spanish, and Shona and contextually adapted …

Whole Genome Sequence Analysis Of Low-Density Lipoprotein Cholesterol Across 246 K Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Carpal Tunnel Syndrome And Occupational Co-Exposure To Biomechanical Factors And Neurotoxic Chemicals Using Job-Exposure Matrices And Self-Reported Exposure: Findings From The Constances Cohort, Julie Bodin, Clémence Rapicault, Alexis Descatha, Marc Fadel, Fabien Gilbert, Bradley Evanoff, Nathalie Bonvallot, Marcel Goldberg, Marie Zins, Yves Roquelaure

2020-Current year OA Pubs

OBJECTIVE: To study the association between occupational co-exposure to biomechanical risk factors, potentially neurotoxic chemicals and carpal tunnel syndrome (CTS) in a large cohort of French workers, using two methods to estimate chemical exposure: job-exposure matrices (JEM) and self-reported exposure.

METHODS: A randomly selected sample of adults were included between 2012 and 2018 in the French cohort CONSTANCES. Self-reported CTS was assessed using the first self-administered follow-up questionnaire, sent out approximately one year after baseline. Occupational exposure to biomechanical risk factors was assessed using self-administered questionnaire completed at inclusion. Lifetime occupational exposure to chemicals was assessed using two different methods: …

Mechanisms And Environmental Factors Shaping The Ecosystem Of Brain Macrophages, Silvia Penati, Simone Brioschi, Zhangying Cai, Claudia Z Han, Marco Colonna

2020-Current year OA Pubs

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated macrophages (BAMs) in the extra-parenchymal compartments. These cells play crucial roles in maintaining brain homeostasis and immune surveillance. Microglia and BAMs are phenotypically and epigenetically distinct and exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both microglia and BAMs originate from the same myeloid progenitor during yolk sac hematopoiesis, but their developmental fates diverge within the brain. Several works have partially unveiled the mechanisms orchestrating the development of microglia and BAMs in both mice and humans; however, many questions remain unanswered. …

Case Report: Molecular Characterization Of Adult Atypical Teratoid Rhabdoid Tumor And Review Of The Literature, Miguel A Hernandez-Rovira, Michelle Connor, Robert C Osorio, Emilie Russler-Germain, Robert Schmidt, Gabrielle W Johnson, Julie Silverstein, Sonika Dahiya, Nyssa Fox Farrell, Mia C Weiss, Gregory J Zipfel, Jiayi Huang, Dimitrios Mathios

2020-Current year OA Pubs

BACKGROUND AND IMPORTANCE: Atypical teratoid rhabdoid tumors (ATRTs) are typically aggressive pediatric tumors with a median survival of 11 months. Due to the paucity of cases in adults, the clinical behavior of these pathologies is not well understood. Here we present the case of a 41-year-old female patient with postoperative hyperprogression of a sellar ATRT and provide a detailed description of the molecular composition of this tumor, the protocol used to treat this patient, and the ultimate outcome of this patient.

CLINICAL PRESENTATION: The patient is a 41-year-old woman who presented with headaches and double vision. MRI revealed a sellar/suprasellar …

Case Report: Rosah Syndrome Presents Diagnostic And Therapeutic Challenges, Jenny Shunyakova, Margaret Reynolds, Amal Taylor, Erin G Sieck, James T Walsh, Lynn M Hassman

2020-Current year OA Pubs

BACKGROUND: Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is an autosomal dominant disorder caused by a heterozygous missense mutation in alpha kinase 1 (ALPK1). This series reports the presentation and treatment outcomes of three first-degree relatives with ROSAH syndrome.

METHODS: Retrospective chart review, whole exome sequencing.

RESULTS: A 16-year-old male presented with bilateral optic disc edema, macular edema, retinal degeneration, and vitreous inflammation. His mother and brother had similar clinical features. Whole exome gene sequencing identified a shared heterozygous mutation in the ALPK1 gene c.710C>T, consistent with ROSAH syndrome. Ophthalmic manifestations in this family included …