Digital Commons Network^™

Surgeon Interpretation Of Patient-Reported Outcome Measures In Upper Extremity Osteoarthritis, Rick S. Looman, Koen Oude Nijhuis, Sina Ramtin, David Ring, Daniel A. London, Ryan Calfee, Niels Brinkman, Science Of Variation Group

2020-Current year OA Pubs

PURPOSE: Measures that quantify levels of pain intensity, incapability, symptoms of distress, and unhelpful thinking were designed as research tools. We studied how surgeons interpret and act on these scores in the care of individual patients.

METHODS: In an online experiment, 67 upper limb specialists from the Science of Variation Group reviewed 10 fictious patient scenarios of trapeziometacarpal, wrist and elbow osteoarthritis (OA) and randomized elements of radiographic severity, levels of discomfort and incapability, deprivation index score (social health), and levels of distress and unhelpful thinking (mental health). Multilevel mixed-effects linear regression identified patient factors associated with surgeon concern, enthusiasm …

A Holistic Ecosystem Model To Diversify The Physician Workforce And Enhance Health, Erik J Porfeli, Sunny Nakae, Leila Amiri, Leila E Harrison, Will Ross

2020-Current year OA Pubs

IMPORTANCE: The U.S. medical education system attracts and trains the next generation of physicians to advance the health care needs of a growing and increasingly diverse nation. This system can be credited for supplying a physician workforce achieving remarkable growth and innovation, yielding one of the world's most technologically advanced health care systems on the planet. This system, unfortunately, also contributes to educational, workforce, and health disparities.

OBSERVATIONS: The successes and challenges of the medical education and health care system align with broader economic, health, and educational patterns in the United States. An ecological model can be employed to unite …

Sociodemographic Factors Predict Outcomes And Reveal Spatial Tumor Patterns In Glioblastoma, Patrick H Luckett, Michael Olufawo, Noah Naddaff-Slocum, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) is the deadliest malignant glioma of the central nervous system. Postsurgical functional impairment correlates with survival and is estimated using metrics such as extent and location of resection. This study uses machine learning to evaluate the predictive ability of baseline sociodemographic and lifestyle factors for forecasting postoperative functional outcomes in GBM patients.

METHODS: Glioblastoma patients (

RESULTS: Utilizing decision trees with age, SVI/SES, sex, tobacco use, alcohol use, obesity, and race as predictors, we achieved 88% accuracy in classifying median KPS and 85% accuracy in classifying KPS slope. Socioeconomic factors were the strongest predictors. Age, sex, and …

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

Zika Virus Encephalitis Causes Transient Reduction Of Functional Cortical Connectivity, Shannon C Agner, Lindsey M Brier, Jeremy D Hill, Ethan Y Liu, Annie Bice, Rachel M Rahn, Shengxuan Chen, Joseph P Culver, Robyn S Klein

2020-Current year OA Pubs

SIGNIFICANCE: Determining the long-term cognitive impact of infections is clinically challenging. Using functional cortical connectivity, we demonstrate that interhemispheric cortical connectivity is decreased in individuals with acute Zika virus (ZIKV) encephalitis. This correlates with decreased presynaptic terminals in the somatosensory cortex. During recovery from ZIKV infection, presynaptic terminals recover, which is associated with recovered interhemispheric connectivity. This supports the contribution of synapses in the cortex to functional networks in the brain, which can be detected by widefield optical imaging. Although myeloid cell and astrocyte numbers are still increased during recovery, RNA transcription of multiple proinflammatory cytokines that increase during acute …

Slc35a2 Gene Product Modulates Paramyxovirus Fusion Events During Infection, Yanling Yang, Yuchen Wang, Danielle E. Campbell, Heng-Wei Lee, Wandy Beatty, Leran Wang, Megan Baldridge, Carolina B. López

2020-Current year OA Pubs

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed …

Usability Of The Mayo Test Drive Remote Self-Administered Web-Based Cognitive Screening Battery In Adults Aged 35-100 With And Without Cognitive Impairment, Jay S Patel, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mayo Test Drive (MTD): Mayo Test Development through Rapid Iteration, Validation and Expansion, is a web-based remote cognitive assessment platform for self-administered neuropsychological measures with previously demonstrated validity and reliability. We examined the usability of MTD and hypothesized that completion rates would be greater than 90%. We explored whether completion and participation rates differed by cognitive status and demographic factors.

METHODS: A total of 1,950 Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center participants (97% White, 99% Non-Hispanic) were invited to participate in this ancillary, uncompensated remote study. Most invitees were cognitively unimpaired (CU;

RESULTS: Baseline …

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.

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 …

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 …

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.

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. …

Defining Knowledge Gaps In Preterm Birth Research: Can Biomarkers Fill The Gaps?, Scott M Williams, Kevin P Rosenblatt, Sandra Reznik, Dawn P Misra, Shajila Siricilla, Nardhy Gomez-Lopez, Brandie D Taylor, Kristina M Adams Waldorf, Ramkumar Menon, Prebic North America 2024

2020-Current year OA Pubs

Preterm birth (PTB) is a syndrome arising from multiple etiologies that manifest as a final common phenotype, delivery before full term. Current knowledge gaps in epidemiologic, basic science, and clinical fields have limited our understanding of this complex pregnancy syndrome. Lack of insight into the cellular and molecular pathways underlying spontaneous PTB (PTB) has thus limited effective clinical management and restricted the investigation of novel treatments or druggable targets. Here, we examine several areas of domain-driven research that may lead to a better understanding of PTB, including infection and inflammation that drive early labor, social factors and their biological consequences …

A Multicenter Study To Assess Efficacy, Safety, And Tolerability Of Ropeginterferon Alfa-2b-Njft In Patients With Essential Thrombocythemia In The Us And Canada: Exceed-Et Trial, Lucia Masarova, Stephen T Oh, Et Al.

2020-Current year OA Pubs

No abstract provided.

"I Feel Like People Would Look At Me Like I'M Dirty Or Like I'M A Thief:" A Qualitative Exploration Of Interpersonal And Intrapersonal Experiences That Influence Recovery Among Adults At Risk Of Opioid-Related Overdose, Hannah S Szlyk, Sara Jones, Jordan Michener, Zhuoran Zhang, Nina Kaiser, Heidi Holtz, Melody Rachel Konadu Frempong, Husain Lateef, William Hutson, Patricia Cavazos-Rehg

2020-Current year OA Pubs

OBJECTIVE: Due to the nature of early termination of treatment and the transient lifestyles of many people who use substances, many providers are unaware of the factors that may have contributed to their client's engagement in treatment. Treatment providers and researchers need a better understanding of intrapersonal and interpersonal factors that impact recovery from the clients' perspective. This study uses qualitative methods to explore these factors.

METHODS: Eligible participants were adults who had used opioids and/or stimulants and were receiving treatment at a consenting facility. Participants completed one-month follow-up interviews after using a mobile health intervention. Transcripts were analyzed using …

Upper Limb Motor Recovery In Chronic Stroke-Longitudinal Aggregate Analysis From Control Group Outcomes, Fabien Scalzo, Robert A Coker, Lauren Souders, Leo Petrossian, Kern Bhugra, Lauren Sheehan, Eric C Leuthardt, Alexander R Carter

2020-Current year OA Pubs

INTRODUCTION: This study examines the effects of regular physical activity on upper extremity motor recovery during the late subacute and chronic phases of stroke.

METHODS: Data were aggregated from 20 studies comprising 368 participants in control groups receiving usual care or general rehabilitation without specialized interventions. To isolate the impact of non-specific physical activity, studies involving robotics or task-specific therapies were excluded.

RESULTS: The primary outcome was the change in Fugl-Meyer Assessment of Upper Extremity (FMA-UE) motor scale. The pooled effect size for FMA-UE change was small and non-significant (Cohen's

DISCUSSION: These findings provide a quantitative benchmark for expected gains …

Assessing The Efficacy Of The Natural Disaccharide Trehalose In Ameliorating Diet-Induced Obesity And Metabolic Dysfunction, Yu-Sheng Yeh, Trent D Evans, Se-Jin Jeong, Ziyang Liu, Ali Ajam, Carlos Cosme, Jun Huang, Doureradjou Peroumal, Xiangyu Zhang, Ali Javaheri, Jaehyung Cho, Irfan J Lodhi, Babak Razani

2020-Current year OA Pubs

Trehalose is a naturally occurring disaccharide with versatile commercial applications and health benefits, including promise as a therapeutic for obesity and diabetes. Although numerous previous reports purport the therapeutic uses of orally ingested trehalose, the abundance of glycosidases in the gastrointestinal tract suggest the potential for significant limitations of oral trehalose that have not been addressed. We first fed mice a high-fat diet (HFD) while providing trehalose by both oral and intraperitoneal routes. This combined strategy was broadly efficacious in reversing HFD-induced weight gain, fat mass, insulin resistance, and the development of hepatosteatosis. In contrast, oral-only trehalose failed to improve …

Bronchus-Associated Lymphoid Tissue In Lung Transplantation: A Facilitator Of Rejection Or Regulator Of Tolerance?, Alexander N Wein, Charles R Liu, Daniel Kreisel

2020-Current year OA Pubs

The role of bronchus-associated lymphoid tissue (BALT) in the regulation of immune responses to transplanted lungs remains an area of interest and controversy. Early studies in a rat pulmonary transplant model suggested BALT may accelerate rejection of grafts by inducing a local and systemic inflammatory response. Such observations were corroborated in intrapulmonary tracheal transplant models in the rat. While some human studies have described the presence of BALT in grafts that have been chronically rejected, others did not observe an association between induction of BALT and adverse outcomes. More recent investigations have found that BALT, enriched in immunoregulatory cell populations, …

Evaluating And Supporting Leadership, Management, And Mentoring: A Framework For Catalyzing Responsible Research And Healthy Research Environments, Tristan Mcintosh, Alison L Antes

2020-Current year OA Pubs

Those who lead research teams have myriad roles and responsibilities that are pivotal to both producing rigorous and responsible scientific work and creating a supportive research environment that cultivates this work. We begin by presenting a leadership, management, and mentoring (LMM) framework focused on three critical roles researchers must play that have direct impact on the scientific work, the work environment, and research team dynamics: the role of research leader, research manager, and research mentor. Research leadership involves fostering a healthy research culture by building relationships where team members feel respected and supported. Research management involves providing oversight and direction …

Characterization Of Tlr9 Responsiveness In Cell Subsets Derived From In Vitro Pdc Differentiation Of Hematopoietic Stem And Progenitor Cells, Sabina Sánchez Hernández, Tobias Wang Bjerg, Ian Helstrup Nielsen, Anders Laustsen, Hai Q Tang, Lars Henning Pedersen, Eynav Klechevsky, Martin R Jakobsen, Rasmus O Bak

2020-Current year OA Pubs

Plasmacytoid dendritic cells (pDCs) are multifunctional immune cells with roles in both the innate and adaptive immune system. Their hallmark function is production of large amounts of type I interferons in response to viral infections, but they are also capable of producing a range of other cytokines, antigen presentation, and cytotoxicity. Their potential as an immunotherapy for cancer and infectious disease is being explored, but broad application of these cells is challenged by low frequency in the blood and low viability during

Structural Diversity Of Axonemes Across Mammalian Motile Cilia, Miguel Ricardo Leung, Chen Sun, Jianwei Zeng, Jacob R Anderson, Qingwei Niu, Wei Huang, Willem E M Noteborn, Alan Brown, Tzviya Zeev-Ben-Mordehai, Rui Zhang

2020-Current year OA Pubs

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii

Enhancing Engagement In Hiv Care Among Adolescents And Young Adults: A Focus On Phone-Based Navigation And Relationship Building To Address Barriers In Hiv Care, Harriet Fridah Adhiambo, Dorothy Imbuka Mangale, Elvin Geng, Et Al.

2020-Current year OA Pubs

Structural, psychological, and clinical barriers to HIV care engagement among adolescents and young adults living with HIV (AYAH) persist globally despite gains in HIV epidemic control. Phone-based peer navigation may provide critical peer support, increase delivery flexibility, and require fewer resources. Prior studies show that phone-based navigation and automated text messaging interventions improve HIV care engagement, adherence, and retention among AYAH. However, little is known about AYAH experiences utilizing electronic phone-based peer navigation and automated text messaging (E-NAV). We assessed the experiences of AYAH receiving phone-based peer navigation to address barriers to HIV care engagement and viral suppression. We purposefully …

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A. Rosa, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …