Digital Commons Network^™

Preoperative Imaging For Cochlear Implantation: A Global Consensus, Farid Alzhrani, Craig Buchman, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Preoperative imaging is vital for cochlear implant surgeries, aiding diagnosis, and surgical planning. This study evaluated global practices and the value of preoperative imaging through an international survey.

METHODS: A cross-sectional survey was conducted among international cochlear implantation experts using a 112-item questionnaire. The study explored imaging modalities, anatomical targets, evaluated parameters, and different imaging approaches' perceived value and risks. Participants were recruited from a global consortium of otolaryngology, otology, neurotology, and cochlear implant surgery professionals.

RESULTS: Thirty-nine practitioners from 36 centers in 16 countries completed the survey (95.1% response rate). All used computed tomography (CT) and magnetic resonance …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Neurofibromatosis Type 1-Plexiform Neurofibromas: Integrating Treatment Across Pediatric And Adult Populations, Amy E Armstrong, Andrea M Gross, Laura J Klesse, Steven D Rhodes, Shivani Ahlawat, Verena Staedtke, Camilo A Molina, Angela C Hirbe

2020-Current year OA Pubs

Plexiform neurofibromas (PNs) are a hallmark of neurofibromatosis type 1 (NF1), affecting ∼50% of individuals with the condition. Originating from Schwann cells and other peripheral nerve sheath components, these tumors can cause significant morbidity, including functional impairment, diminished health-related quality of life, chronic pain, and malignant transformation. Managing NF1-PNs is challenging because of disease variability, differing growth rates, and age-related differences in clinical presentation and treatment tolerability. This review examines current therapeutic strategies, including surgery, medical therapies, and emerging treatments, emphasizing individualized care. Highlighted here is the need for age-specific treatment planning, particularly as disease progression, comorbidities, and side-effect profiles …

A Treat-To-Target Approach For Obesity Management: A Post Hoc Analysis Of The Surmount-5 Trial., Carel W Le Roux, Luca Busetto, Louis Aronne, Deborah Bade Horn, Georgios K Dimitriadis, Beverly Falcon, Luis-Emilio Garcia-Perez, Elisa Gomez Valderas, Theresa Hunter Gibble, Cagri Senyucel, Julia P Dunn

Faculty, Staff and Student Publications

Introduction: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide.

Methods: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) < 0.53, body mass index (BMI) < 27 kg/m2, or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored.

Results: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR < 0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS.

Conclusion: In this …

An International Mega-Analysis Of Psychedelic Drug Effects On Brain Circuit Function, Manesh Girn, Nico Dosenbach, Et Al.

2020-Current year OA Pubs

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …

Neuropsychiatric Symptoms Mimicking Dementia In A Patient Treated With Imatinib, Ashley Jones, Samuele Bonomi, Keith E Stockerl-Goldstein, Randall J Bateman

2020-Current year OA Pubs

Tyrosine kinase inhibitors are the cornerstone of chronic myeloid leukemia treatment. Newer agents have more potency and a broader spectrum of action, but also a higher potential for neuropsychiatric side effects. We present a case of a patient on imatinib who developed progressive cognitive, mood, and behavioral alterations. He was investigated for dementia and psychiatric disorders but ultimately improved only after discontinuing imatinib. His decompensation years after therapy start, followed by complete and rapid remission, is atypical. We also review the most recent neurobiological findings on the role of tyrosine kinase alterations in dementia and their importance for mood regulation.

Sensitivity And Concordance Study Of An Open Source Epid-Based Linear Accelerator Test Suite, Lana C Critchfield, Cory S Knill, Ellie Durussel, Justin K Mikell, Michael Barnes, Michael Pillainayagam, William P Donahue, Seng Boh Lim, John J Demarco, Mario Perez, Nilendu Gupta, Hania Al-Hallaq, Richard A Popple, Jim Irrer, Jean M Moran

2020-Current year OA Pubs

BACKGROUND: Electronic portal imaging devices (EPIDs) enhance linear accelerator (linac) quality assurance (QA) efficiency but are not universally used beyond patient-specific IMRT QA. A multi-institutional Consortium seeks to standardize linac QA utilizing an EPID-based test suite.

PURPOSE: This study evaluates the sensitivity of a test suite to intentional linac and plan errors and the concordance with linac fluctuations over time.

METHODS: Baseline and error-introduced tests were performed on a Varian TrueBeam and Clinac. Evaluated parameters included enhanced dynamic wedge factors (EDW) (6MV), central axis dose (6MV, 6MV FFF, 16MV), focal spot alignment and beam symmetry (6MV, 16MV), dose rate-gantry speed …

Apoe-Stratified Proteomic And Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation And Lipid Dysregulation In Alzheimer's Disease, Fuhai Li, Yike Chen, Daniel Western, Muhammad Ali, Menghan Liu, Katherine Gong, Ying Xu, Joseph Lowery, David M Holtzman, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-dependent and independent effects is instrumental for understanding the biology of AD. We conducted an APOE-stratified multi-omic analysis in multiple large datasets to identify AD-associated plasma proteins and metabolites. More than 64% of the identified proteins were not found in non-APOE stratified studies, and 17% of the proteins showed APOE-specific trends. Mitochondrial dysfunction was associated in AD independently of APOE and was accompanied by disruptions in glucose and lipid …

The Femoral Head Edema Zone: A Novel Classification Scheme To Better Predict Osteonecrosis Progression, Deniz C Ince, Vivek P Shah, Kenichi Kikuchi, Kyle P O'Connor, Elizabeth L Yanik, John C Clohisy, Cecilia Pascual-Garrido

2020-Current year OA Pubs

BACKGROUND: This study proposed a new classification, the Edema Zone classification, that uses magnetic resonance imaging images to grade the extent of edema in osteonecrosis of the femoral head. The purpose of the study was (1) to examine how the Edema Zone classification compared to the Japanese Investigation Committee (JIC) classification's prognostic ability for early conversion to total hip arthroplasty (THA), and (2) to determine how accurately and reliably the Edema Zone classification performed as a classification system.

METHODS: This was a retrospective study of hips that converted to THA from a core decompression within 26 months compared to hips …

Quality Of Antenatal And Delivery Care And Postnatal Care Use: A Multi-Country Observational Study Of 400,000 Births, Jan E. Cooper, Hwa-Young Lee, Katherine Wright, Prashant Jaryan, Margaret E. Kruk

2020-Current year OA Pubs

BACKGROUND: Postnatal care (PNC) plays a crucial role in averting newborn mortality, yet its use remains low, particularly in regions with the highest mortality. While demographic and social determinants of PNC use have been well studied and have informed current strategies focused on changing care-seeking behaviors, the stagnating decline in neonatal mortality highlights the need for upstream and system-wide approaches to increase PNC uptake. Limited evidence exists to guide system-level reforms; therefore, we investigated whether health systems that ensure high-quality perinatal care are associated with increased use of PNC.

METHODS AND FINDINGS: We performed a cross-sectional observational study using Demographic …

Lessons Learned From The Implementation Of A Pragmatic Trial Evaluating Non-Pharmacological Approaches To Dementia Care In Us Nursing Homes, Carin Wong, Catherine V. Piersol, Felicia Chew, Cara Lekovitch, Victoria Shier, Mike Morris, Jenny Martínez, Julie Britton, Natalie E. Leland

Department of Occupational Therapy Faculty Papers

RATIONALE: The consistent delivery of effective evidence into nursing home practice has been shown to enhance quality of care and residents' outcomes. Pragmatic trials enable the evaluation of efficacious interventions in a real-world context, including care of residents living with Alzheimer's Disease and Related Dementias (ADRD). Yet, there are limited pragmatic trials conducted in nursing homes and even less evidence on the strategies to successfully conduct such research in this setting.

OBJECTIVE: To identify the lessons learned from a pragmatic trial and provide recommendations for future successful studies in United States (US) nursing homes.

METHODS: Drawing on a case example …

Acute Myocardial Infarction In Medicare Beneficiaries During And After The Covid-19 Pandemic, Jonah M Graves, R J Waken, Fengxian Wang, Rishi K Wadhera, Jose F Figueroa, E John Orav, Osvaldo J Laurido-Soto, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: During early months of the COVID-19 pandemic, presentations for acute myocardial infarction (AMI) declined significantly, and outcomes worsened. However, the full extent and long-term sequelae of changes in AMI epidemiology during the pandemic remain uncertain, as does whether these patterns differed by rurality.

OBJECTIVE: To describe the epidemiology of AMI-related hospitalizations, interventions, and outcomes among Medicare beneficiaries throughout the COVID-19 pandemic, focusing on differences in urban and rural populations.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included all Medicare fee-for-service beneficiaries with AMI between January 1, 2018, and December 31, 2023, in the analysis. Data were analyzed from …

Performance Of Multiple Multi-Cancer Detection Tests Using A Large Independent Reference Set (Alliance A212102), Marie E Wood, Mark Watson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials.

METHODS: Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect ("targeted"), plus additional "non-targeted" and control samples. Companies reported …

Hepatitis C Virus Testing In Perinatally Exposed Children, Rachel L Epstein, Sarah Munroe, Elizabeth A Erdman, Amy Bettano, Megan R Curtis, Laura White, Elisha M Wachman, Anthony Osinski, Alexander Y Walley, Benjamin P Linas

2020-Current year OA Pubs

IMPORTANCE: Despite rising hepatitis C virus (HCV) incidence in pregnant people, studies demonstrate that fewer than 50% of perinatally exposed infants receive HCV testing. Few studies report treatment of infected infants or factors affecting testing.

OBJECTIVE: To identify birthing parent and child factors associated with appropriate HCV testing for perinatally exposed infants and characterize HCV care for children with HCV.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included records on testing, care, and treatment for Massachusetts children perinatally exposed to HCV between 2014 and 2021 from a statewide health database linking statewide vital statistics, infectious disease surveillance data, substance use …

Mda5-Mavs And Interferon-Lambda Signaling In The Intestinal Epithelium Limit Murine Astrovirus Infection, Heyde Makimaa, Harshad Ingle, Leran Wang, Somya Aggarwal, Hongju Deng, Elizabeth A Kennedy, Lynne Foster, Yuhao Li, Megan T Baldridge

2020-Current year OA Pubs

Human astroviruses (HAstVs) are a global cause of pediatric gastroenteritis and can cause disseminated infection in immunocompromised hosts. Murine astrovirus (muAstV) causes acute asymptomatic infections in immunocompetent mice and chronic infection in immunodeficient models and has provided important insights into AstV pathogenesis in vivo. MuAstV can protect immunodeficient mice from other enteric viruses via robust induction of antiviral cytokine interferon-lambda (IFN-λ), with recent findings implicating goblet cells and enterocytes as both cell types infected by muAstV as well as potential sources of IFN-λ in vivo. However, the viral sensing pathways that regulate induction of IFN-λ, as well as the specific …

Intracranial Mesenchymal Tumor, Fet::Creb Fusion-Positive: An Integrative Analysis Of 81 Cases, Sharika Rajan, Robert Schmidt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1, or CREM). The methylation signature(s), gene expression characteristics, and clinical behavior of this important tumor type require further characterization.

METHODS: We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available.

RESULTS: ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified …

Differential Regulation Of Cyclic Adenosine Monophosphate By Phosphodiesterase 3a Discriminates Thrombin-Induced Protease Activated Receptor 1- And 4-Dependent Platelet Activation, Izabella Andrianova, Abigail Ajanel, Jesse W Rowley, Darian C Murray, Yasuhiro Kosaka, Frederik Denorme, Paul F Bray, Robert A Campbell

2020-Current year OA Pubs

BACKGROUND: Human platelets express 2 thrombin-activated G protein-coupled receptors (GPCRs), protease activated receptor (PAR)1 and PAR4. Previous studies have demonstrated PAR1 activation to be fast on-fast off while PAR4 activation was slower but more sustained. However, how PARs regulate second messengers such as cyclic adenosine monophosphate (cAMP), a negative regulator of platelet activation, remain unknown.

OBJECTIVES: This study investigated how PAR1 and PAR4 activation by thrombin regulates cAMP levels and platelet activation.

METHODS: PAR1 and PAR4 on washed human platelets were inhibited with vorapaxar or BMS-986120, respectively, in the presence or absence of prostaglandin (PG)I

RESULTS: In the presence of …

Lyplal1 Rare Loss-Of-Function Variants In Humans And Deletion In Human Hepatoma Cells Protect Against Masld, Rawdat Hussain, Chinmay Raut, Ponnandy Prabhu, Akram Irshaid, Yash Hegde, Yue Chen, Asmita Pant, Antonino Oliveri, Xiaochao Wei, Lishi Yin, Tiffany L Russell, Brian Halligan, Clay F Semenkovich, Elizabeth K Speliotes

2020-Current year OA Pubs

Genetic variants near LYPLAL1 are associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in humans, but their impact on LYPLAL1 function is unknown. We identified LYPLAL1 loss-of-function variants from UK BioBank (UKBB) whole-exome sequencing data that had AlphaMissense or GPN-MSA scores in the top 20% of LYPLAL1 variants for being disruptive. We aggregated these variants and carried out burden analysis for effects on MRI Proton Density-Fat Fraction (MRI-PDFF) and ICD-based MASLD in UKBB. Rare loss-of-function LYPLAL1 variants were associated with reduced MRI-PDFF and ICD diagnosed MASLD across sexes. We used CRISPR to knockout and overexpress LYPLAL1 in human hepatoma cells …

Promoting Community And Social Participation In Chronic Stroke: A Pilot Study Of The Engage Intervention, Elizabeth Skidmore, Carolyn Baum, Jessica Kersey, Emily Kringle, Kelsey Voltz-Poremba, Sular Gordon, Tina Harris, Heidi Fischer, Maureen Gecht, Michelle Furman, Joy Hammel

2020-Current year OA Pubs

BACKGROUND: Survivors of stroke report low levels of community and social participation, even years after stroke. ENGAGE is a community-based intervention that merges social learning, guided problem solving, and supervised practice to collaboratively identify, generate, and apply solutions to challenges with community and social participation after stroke.

OBJECTIVE: We examined the feasibility, acceptability, and safety of ENGAGE and characterized within group changes in community and social participation outcomes.

METHODS: Community-dwelling survivors of stroke, occupational therapy providers, and occupational therapy scientists partnered to co-design the essential and structural elements of ENGAGE, as well as to evaluate ENGAGE using a multi-site single-arm …

Deep Learning In Fetal, Infant, And Toddler Neuroimaging Research, Jenna H Chin, Madeleine K Wyburd, Vladislav Ayzenberg, Laurie Bayet, Berkin Bilgic, Emily M Chen, Yuting Chen, Áine Dineen, Shohei Fujita, Janelle Liu, Yohan Jun, M Catalina Camacho, Lilla Zöllei

2020-Current year OA Pubs

Artificial intelligence (AI) is increasingly being integrated into everyday tasks and work environments. However, its adoption in medical image analysis has progressed more slowly due to high clinical stakes, limited availability of labeled data, and substantial variability in imaging protocols and population. These challenges are further pronounced in the field of fetal, infant, and toddler (FIT) neuroimaging, where datasets are especially scarce and subject to large amounts of anatomical variability. However, deep learning (DL), a specific method within machine learning, which is itself a subfield of AI, has emerged as a powerful framework to adapt to the challenges of medical …

De Novo Heterozygous Variants Of The Rsf1 Gene Are Responsible For A Syndromic Neurodevelopmental Disorder, Céline Jost, Daniel Wegner, Marwan Shinawi, Kathleen Sisco, Alexander J Paul, Et Al.

2020-Current year OA Pubs

Neurodevelopmental disorders (NDD) are a wide and heterogenous group of conditions due to impaired brain development, orchestrated by the crosstalk between genome and environment. Dynamic chromatin regulation during cortical development is fundamental, and chromatin remodelers are critical determinants of this process. Recently, numerous chromatin remodeling genes have been implicated in NDDs. By altering genes' epigenetic state, mutated chromatin remodelers disrupt the spatiotemporal regulation of gene expression during development, potentially leading to severe consequences. The Remodeling and Spacing Factor 1 (RSF1) gene encodes a ubiquitous nuclear protein involved in chromatin remodeling, crucial for processes such as DNA transcription, replication, and repair. …

Methodological Progress Note: Logic Models, Molly J Horstman, Kyler M Godwin

Faculty and Staff Publications

Logic models are an accessible tool to organize the planning, management, and evaluation of programs across healthcare disciplines. This methodological progress note describes the five standard components of a logic model (Inputs, Activities, Outputs, Outcomes, and Impact) and provides guidance for developing a logic model. Logic models offer a visual representation of the work and theory of a program and should be created with input from all interested parties. Logic models are living tools that need to be revised as programs evolve and new information becomes available.

Use Of Inverse Probability Weighting In Cardiovascular Surgical Outcomes Research: Principles, Limitations, And Recommendations, Zhongjian Liu, Wei-Guo Ma, Lei Liu, Prashanth Vallabhajosyula, Haibo Wang

2020-Current year OA Pubs

This statistical primer presents a comprehensive introduction to the use of inverse probability of treatment weighting (IPTW), a method for rebalancing group confounders at baseline in cardiovascular surgical outcomes research. We leveraged a retrospective study comparing the outcomes of 2 different surgical approaches to aortic arch pathology to illustrate the essential aspects of performing IPTW, including basic theories, application, extreme weights, underestimated variance, heterogeneity of treatment effect, and multicollinearity. The limitations of IPTW were discussed with examples of solutions. Ten practical recommendations are made on avoiding the pitfalls in the use of IPTW. Proper use of IPTW may effectively reduce …

Ethical Controversies In Organ Procurement: A National Survey On Public Perceptions Of Thoracoabdominal Normothermic Regional Perfusion, Trevor M Bibler, Jill Oliver Robinson, Adam Omelianchuk, Tariq Nisar, Savitri Fedson, Ariel N Levchenko, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Thoracoabdominal normothermic regional perfusion (TA-NRP) would likely expand the quantity and quality of organs procured after controlled circulatory death donation in the United States, yet its ethical permissibility remains contested. We surveyed a representative sample of US adults (n = 975) with the goal of assessing their perspectives on the ethical permissibility of TA-NRP. After reading a neutral description of TA-NRP, participants judged its permissibility, reviewed 5 critic and 5 supporter arguments (in random order), and chose which argument they found most convincing. Multivariable logistic regression examined predictors of agreeing with critics. Before exposure to the arguments, 51.5% stated that …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

2020-Current year OA Pubs

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …

Mechano Responsiveness Of Neuroimmune Cross-Talk In Bone And Joints: A Narrative Review With Implications For Force-Based Manipulations, Karl J Lewis, Jennifer Bent, Per Gunnar Brolinson, Damian Keter, Ellen Lumpkin, Jan Mundo, Vitaly Napadow, William R Reed, Brent S Russell, Simon Y Tang, Mary F Barbe

2020-Current year OA Pubs

INTRODUCTION: Recent advances in osteoimmunology have illuminated the significant role of neuroimmune interactions in bone and joint health. The neuroimmune system critically regulates bone cell function through a complex network of molecular mediators - including signals from the sympathetic and parasympathetic nervous systems, pro- and anti-inflammatory cytokines, cortisol and other hormones, and growth factors. These mediators interact within a nonlinear network where each component can influence others reciprocally, with the brain serving as a central coordinator.

AIM: Our goal in this narrative review is to: 1) Provide an overview of roles the neuroimmune system is involved in bone and joint …

Body Mass Index And Survival In Children Receiving Extracorporeal Membrane Oxygenation, Pilar Anton-Martin, Keith Baxelbaum, Shilpa Vellore, Erika O'Neil, Vinai Modem, Sameer Thadani

Faculty, Staff and Students Publications

Importance: Underweight and obesity represent opposite ends of the nutritional risk spectrum that negatively affect children's health worldwide. Both conditions have been associated with increased mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

Objective: To investigate the association of underweight and obesity status with pediatric ECMO outcomes using body mass index (BMI) z scores.

Design, setting, and participants: This retrospective cohort analysis used data from the Extracorporeal Life Support Organization (ELSO) database from January 1, 2019, to December 31, 2023. Participants included all pediatric patients from international ECMO centers aged 29 days to 18 years who received ECMO …

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …