Medicine and Health Sciences Commons^™

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Preliminary Investigation Of Obstructive Sleep Apnea And Alzheimer's Disease In Down Syndrome, Dasoo M Yoon, David T Plante, Victoria Fleming, Benjamin Handen, Patrick Lao, Jamie Peven, Bradley Christian, Ozioma Okonkwo, Charles Laymon, Beau Ances, Christy Hom, Brian Helsel, Sigan L Hartley

2020-Current year OA Pubs

This study provided a preliminary examination of indices of obstructive sleep apsnea (OSA) and sleep disruptions in adults with Down syndrome (DS), and their associations with Alzheimer's disease (AD) pathology and symptomatology. A total of 93 adults with DS (aged 25-61 years) from the Alzheimer Biomarker Consortium-DS completed cognitive assessments, MRI and positron emission tomography (PET) scans (assessing amyloid-beta [Aβ] and tau), and a one-night home sleep study using the WatchPAT-300 device. Study partners also reported on depressive symptoms and diagnoses. Correlational analyses examined relationships between sleep variables, PET biomarkers, and AD symptomatology (cognitive functioning and depressive mood), controlling for …

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 …

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 …

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Tracking The Evolving Role Of Artificial Intelligence In Implementation Science: Protocol For A Living Scoping Review Of Applications, Evaluation Approaches And Outcomes [Version 2; Peer Review: 2 Approved], Guillaume Fontaine, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Artificial intelligence (AI) offers significant opportunities to improve the field of implementation science by supporting key activities such as evidence synthesis, contextual analysis, and decision-making to promote the adoption and sustainability of evidence-based practices. This living scoping review aims to: (1) map applications of AI in implementation research and practice; (2) identify evaluation approaches, reported outcomes, and potential risks; and (3) synthesize reported research gaps and opportunities for advancing the use of AI in implementation science.

METHODS: This scoping review will follow the Joanna Briggs Institute (JBI) methodology and the Cochrane guidance for living systematic reviews. A living scoping …

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.

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer's Disease, Farid Rajabli, Bruno A. Bonitez, Nigel J. Cairns, John C. Morriswashington University School Of Medicine In St. Louis, Carlos Cruchaga, Oscar Harari, Laura Ibanez, Et Al.

2020-Current year OA Pubs

No abstract provided.

Domain Mapping Of Disease Mutations Reveals Pathogenic Sorl1 Variants In Alzheimer's Disease, Olav M. Andersen, Carlos Cruchaga, Maria Victoria Fernandez, Et Al.

2020-Current year OA Pubs

No abstract provided.

Methylome Analysis Of Ftld Patients With Tdp-43 Pathology Identifies Epigenetic Signatures Specific To Pathological Subtypes, Cristina T. Vicente, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

No abstract provided.

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.

Articles That May Change Your Practice: Prehospital Extracorporeal Membrane Oxygenation Alerts And Extracorporeal Cardiopulmonary Resuscitation In Out-Of-Hospital Cardiac Arrest, James L Li, Aaron J Lacy, Bridgette B Svancarek

2020-Current year OA Pubs

No abstract provided.

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 …

Managing Tbsrtc Iii Thyroid Nodules: Evaluating Repeat Fna, Molecular Testing, And Surgery, Christopher Dilli, William Mi, Daniel L Miller

2020-Current year OA Pubs

INTRODUCTION: Thyroid nodules are common, but most are benign. Concerning nodules undergo fine-needle aspiration (FNA) and are classified using The Bethesda System. Nodules with atypia of undetermined significance (AUS) [Bethesda III] have management options including surveillance, repeat FNA, molecular testing, and surgical evaluation. While molecular testing can reduce unnecessary surgeries, it is costly. This retrospective study assessed the feasibility of repeat FNA as a cost-effective alternative.

MATERIALS AND METHODS: We conducted a multi-institutional retrospective study of AUS nodules from 5 hospitals between September 1, 2018, and March 1, 2024. Only initial FNA cases were included; pediatric cases and those lost …

An Exploratory Graphical Analysis Of The Montgomery-Åsberg Depression Rating Scale Pre- And Post-Treatment Using Pooled Antidepressant Trial Secondary Data, David Byrne, Arunangshu Ghoshal, Fiona Boland, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Vincent Mcdarby, Emma Wallace, Frank Doyle

2020-Current year OA Pubs

BACKGROUND: The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) is a commonly used measure of depression in antidepressant clinical trials. Numerous studies have adopted classical test theory perspectives to assess the psychometric properties of this scale, finding generally positive results. However, its network configural structure and stability is unexplored across different time-points and treatment groups.

AIMS: To assess the network structure and stability of the MADRS in clinical settings pre- and post-treatment, and to determine a configurally invariant and stable model across time-points and treatment groups (placebo and intervention).

METHOD: Individual participant data for 6440 participants from 14 clinical trials of …

An Exploration Of Drivers Of Sepsis Outcomes In Racial & Ethnic Minority Populations, Providence Svmc Gme

Abstracts, Posters, Presentations

No abstract provided.

An Atypical Presentation Of Metastatic Gastric Adenocarcinoma Due To Pulmonary Lymphangitic Carcinomatosis, Matthew Moritz, Md, Omar Pandhair, Md

View All Materials

No abstract provided.

Thalamic And Visual Network Dysfunction Relates To Tremor Response In Thalamic Deep Brain Stimulation, Aimee E Morris, Babatunde Adeyemo, Meghan C Campbell, Abraham Z Snyder, Joel S Perlmutter, Jonathan W Mink, Scott A Norris

2020-Current year OA Pubs

BACKGROUND: Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.

METHODS: We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups …

Pediatric Cervical Spine Clearance: A 10-Year Evaluation Of X-Ray In Evaluable Patients At A Level 1 Pediatric Trauma Center, William Starr, Stephanie Iantorno, Jing Wang, Richard Eldredge, Rajiv Iyer, Karch Smith, Natalya Mcnamara, Kezlyn Larsen, Stephen Fenton, Robert Swendiman, Katie Russell

2020-Current year OA Pubs

OBJECTIVES: Cervical spine (c-spine) X-ray (XR) remains an important tool for pediatric trauma patients. XR is a low radiation alternative to multidetector CT (MDCT). Our primary aims were to analyze the sensitivity of a negative c-spine XR and to analyze what factors lead to additional imaging after a negative c-spine XR.

METHODS: A retrospective cohort study was conducted at a level 1 pediatric trauma center from 2012 to 2021. We compared the group with negative c-spine XR and no additional imaging to the group with negative c-spine XR followed by additional c-spine MDCT and/or MRI.

RESULTS: There were 2,081 negative …

Development Of A High-Throughput Platform For Quantitation Of Histone Modifications On A New Qtof Instrument, Emily Zahn, Yixuan Xie, Xingyu Liu, Rashmi Karki, Richard M Searfoss, Francisca N De Luna Vitorino, Joanna K Lempiäinen, Joanna Gongora, Zongtao Lin, Chenfeng Zhao, Zuo-Fei Yuan, Benjamin A Garcia

2020-Current year OA Pubs

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The five histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry (MS)-based approaches, identification and quantification of modified histone peptides remains challenging because of factors, such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks. Here, we describe the development of a new high-throughput method to identify and quantify over 150 modified histone peptides by LC-MS. Fast gradient microflow liquid chromatography and variable window sequential windows acquisition of …

A Clinical Practice Review Of Optimizing The Approach For Correction Of Thoracolumbar Deformity— When And How To Perform Anterior Releases And Fusion, Brian M. Phelps, Munish C. Gupta

2020-Current year OA Pubs

No abstract provided.

Caregiver Worry About Covid-19 As A Predictor Of Social Mitigation Behaviours And Sars-Cov-2 Infection In A 12-City U.S. Surveillance Study Of Households With Children, Steven M Brunwasser, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

METHODS: Data were drawn from a surveillance study of households with children (

RESULTS: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with …

Disclosing Disabilities: Barriers For Medical School Applicants, Sarah Leah Solomon, Aitan E. Magence, Harry Haran, Fern R. Juster, Kristina H. Petersen

2020-Current year OA Pubs

This study investigated the availability of accommodation request procedures for medical school admissions interviews and the accessibility of Technical Standards (TS) for candidates with disabilities (CWD) across Liaison Committee on Medical Education (LCME)-accredited institutions in the United States and Canada. Utilizing a cross-sectional study methodology, surveys were distributed to Deans of Admissions and Disabilities Resource Professionals (DRP) at all LCME-accredited US and Canadian MD programs. Surveys gathered data about interview formats, interview accommodation procedures, and TS accessibility during the 2018-2019 academic year. We received responses from 71 institutions (41.3%), with 56.3% survey completion rate (n = 40). Among respondents, interview …

Comparison And Clinical Applicability Analysis Of All-Posterior, Combined Anterior-Posterior, And Combined Lateral-Posterior Approaches In Adult Spinal Deformities: A Narrative Review, Garrison P. Bentz, Christopher Diaz, Nicholas A. Pollatta, Mark J. Lambrechts

2020-Current year OA Pubs

No abstract provided.

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

Comparative Analysis Of Aav Serotypes For Transduction Of Olfactory Sensory Neurons, Benjamin D W Belfort, Johnathan D Jia, Alexandra R Garza, Anthony M Insalaco, J P Mcginnis, Brandon T Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, Ascent-Pd Investigators, Zhandong Liu, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

A Scoping Review Of The Social Determinants Of Pediatric And Adolescent Obesity, Deepali K Ernest, Elizabeth A Onugha, Bipin Singh, Shreela V Sharma, Jayna M Dave

Faculty, Staff and Student Publications

Context: Social determinants of health (SDOH) play a large role in pediatric and adolescent metabolic health worldwide.

Objective: The study is aimed at exploring key SDOH related to childhood obesity, worldwide.

Methods: Primary research articles from PubMed, Embase, and Medline databases published between 2013 and 2023, had a study population of 0-19-year-olds, and examined the association between WHO-defined SDOH and childhood obesity were included. Non-English papers and those outside WHO-defined SDOHs were excluded. Two reviewers independently performed a blinded screening of titles and abstracts, followed by a full-text assessment of selected articles.

Results: Of the 703 initial articles, 22 duplicates …

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 …