Digital Commons Network^™

Stratification System With Dual Human Endogenous Retroviruses For Predicting Immunotherapy Efficacy In Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial. ERV expression was quantified using the ERVmap algorithm …

A Deconvolution Framework That Uses Single-Cell Sequencing Plus A Small Benchmark Data Set For Accurate Analysis Of Cell Type Ratios In Complex Tissue Samples, Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A Owen, Ivana K Kim, Ana Aparicio, Sanghoon Lee, Anil K Sood, Scott Kopetz, John Paul Shen, John N Weinstein, Margaret M Deangelis, Rui Chen, Wenyi Wang

Faculty, Staff and Student Publications

Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using this well-matched, that is, benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using two benchmark data sets of healthy retinas and …

Precision Data-Driven Modeling Of Cortical Dynamics Reveals Person-Specific Mechanisms Underpinning Brain Electrophysiology, Matthew F Singh, Todd S Braver, Michael Cole, Shinung Ching

2020-Current year OA Pubs

Task-free brain activity affords unique insight into the functional structure of brain network dynamics and has been used to identify neural markers of individual differences. In this work, we present an algorithmic optimization framework that directly inverts and parameterizes brain-wide dynamical-systems models involving hundreds of interacting neural populations, from single-subject M/EEG time-series recordings. This technique provides a powerful neurocomputational tool for interrogating mechanisms underlying individual brain dynamics ("precision brain models") and making quantitative predictions. We extensively validate the models' performance in forecasting future brain activity and predicting individual variability in key M/EEG metrics. Last, we demonstrate the power of our …

Faculty Perceptions On The Roles Of Mentoring, Advising, And Coaching In An Anesthesiology Residency Program: Mixed Methods Study, Sydney Nykiel-Bailey, Kathryn Burrows, Bianca E Szafarowicz, Rachel Moquin

2020-Current year OA Pubs

BACKGROUND: Mentoring, advising, and coaching are essential components of resident education and professional development. Despite their importance, there is limited literature exploring how anesthesiology faculty perceive these practices and their role in supporting residents.

OBJECTIVE: This study aims to investigate anesthesiology faculty perspectives on the significance, implantation strategies, and challenges associated with mentorship, advising, and coaching in resident education.

METHODS: A comprehensive survey was administrated to 93 anesthesiology faculty members at Washington University School of Medicine. The survey incorporated quantitative Likert-scale questions and qualitative short-answer responses to assess faculty perceptions of the value, preferred formats, essential skills, and capacity for …

Translation Of Oral Health Research Priorities Into Research Topics In An Equity-Based Priority Setting Exercise, Sumanth Nagraj Kumbargere, Cath Quinn, Lynne Callaghan, Martha Paisi, Mona Nasser

Peninsula Dental School

BACKGROUND: In the context of research priority-setting, participants express their research priorities and ideas in various forms, ranging from narratives to explicit topics or questions. However, the transition from these expressions to well-structured research topics or questions is not always straightforward. Challenges intensify when research priorities pertain to interventions or diagnostic accuracy, requiring the conversion of narratives into the Participant, Intervention, Comparator, Outcome (PICO) format.

SCOPE AND FINDINGS: This project aimed to understand the challenges of engaging a diverse, multilingual population in setting oral health research priorities. While not a comprehensive priority-setting effort, we modified James Lind Alliance's (JLA) methods …

Gut Microbial Changes Associated With Obesity In Youth With Type 1 Diabetes, Heba M Ismail, Dimuthu Perera, Rabindra Mandal, Linda A Dimeglio, Carmella Evans-Molina, Tamara Hannon, Joseph Petrosino, Sara Javornik Cregeen, Nathan W Schmidt

Center for Medical Ethics and Health Policy Staff Publications

Context: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D.

Objective: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-< 85%) vs those with obesity (BMI: ≥95%).

Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in …

Gut Microbial Changes Associated With Obesity In Youth With Type 1 Diabetes, Heba M Ismail, Dimuthu Perera, Rabindra Mandal, Linda A Dimeglio, Carmella Evans-Molina, Tamara Hannon, Joseph Petrosino, Sara Javornik Cregeen, Nathan W Schmidt

Faculty, Staff and Students Publications

Context: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D.

Objective: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-< 85%) vs those with obesity (BMI: ≥95%).

Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in …

Pediatric Papillary Thyroid Carcinoma: Outcomes After Surgery Without Adjuvant Radioactive Iodine, Luz E Castellanos, Mark E Zafereo, Erich M Sturgis, Jennifer R Wang, Anita K Ying, Steven G Waguespack

Faculty, Staff and Students Publications

Context: Pediatric papillary thyroid carcinoma (PTC) is usually treated with total thyroidectomy followed by radioactive iodine (RAI). Recently, RAI has been used more selectively based on surgical pathology and postoperative dynamic risk stratification (DRS).

Objective: To describe patients with pediatric PTC not initially treated with RAI and their disease outcomes.

Methods: This was an ambispective study at a tertiary cancer center of patients < 19 years diagnosed from January 1, 1990, to December 31, 2021, with stage 1 PTC who intentionally were not treated with RAI within a year of diagnosis. We assessed clinical characteristics, management, and disease outcomes using DRS.

Results: Of 490 PTC patients, we identified 93 eligible patients (median age at diagnosis 16 years; 87% female), including 46 (49%) with cervical lymph node metastases. Initial management included total thyroidectomy ± neck dissection (n = 69, …

Steroid Profiling And Circadian Cortisol Secretion In Patients With Mild Autonomous Cortisol Secretion: A Cross-Sectional Study, Jasmine Saini, Sumitabh Singh, Andreas Ebbehoj, Catherine D Zhang, Rohit Nathani, Vanessa Fell, Elizabeth Atkinson, Sara Achenbach, Ann Rivard, Ravinder Singh, Stefan Grebe, Irina Bancos

Faculty, Staff and Students Publications

Context: Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol >1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS.

Objective: To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects.

Methods: Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index-, and menopausal status-matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

Glofitamab In Relapsed/Refractory Mantle Cell Lymphoma: Results From A Phase I/Ii Study, Tycel Jovelle Phillips, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL.

METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and …

Resurgence Of Pediatric Mycoplasma Pneumoniae Infections In Southeast Texas, November 2023-June 2024, Margaret Taylor Danner, Heather Colvin Binns, Khanh Nguyen, Coreen Johnson, Jim Dunn, Denver Niles, Diana K Nguyen

Faculty, Staff and Students Publications

We conducted a retrospective review of children tested for Mycoplasma pneumoniae from January 1, 2020 to June 30, 2024. M. pneumoniae polymerase chain reaction positivity increased starting in November 2023, peaking at 18.3% in June 2024. During the resurgence, children with laboratory-confirmed infection often had severe respiratory disease or extrapulmonary manifestations.

Federally Qualified Health Center Patients’ Experiences With Remote Patient Monitoring As Part Of Telehealth Services For Self-Measured Blood Pressure Monitoring, Natalia I Heredia, Maria E Fernandez, Ella R Garza, Jabria Pittman, Fernanda Velasco-Huerta, Tracy L Judd, Jocelyn Hunyadi, Elvis Longanga Diese, Deevakar Rogith, William B Perkison, Susan H Fenton

Faculty, Staff and Student Publications

BACKGROUND: Remote patient monitoring (RPM) for hypertension management has become increasingly popular, demonstrating benefits for both clinics and patients. However, patient engagement in self-measured blood pressure (SMBP) monitoring remains low despite healthcare providers' efforts. This study aimed to assess adherence and acceptance of RPM for SMBP among Texas Federally Qualified Health Center patients.

METHODS: Participants enrolled in the SMBP monitoring program were recruited at three health centers. Data was collected from patient health records, and a questionnaire assessed hypertension self-management, technology acceptance, intentions, and attitudes toward SMBP. Thematic analysis was conducted for open-ended responses that followed each item, and multivariate …

A Data-Driven Latent Variable Approach To Validating The Research Domain Criteria Framework, S K L Quah, B Jo, C Geniesse, L Q Uddin, J A Mumford, D M Barch, D A Fair, I H Gotlib, R A Poldrack, M Saggar

2020-Current year OA Pubs

Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns, we employ a latent variable approach using bifactor analysis. We examine 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with 6192 participants. A curated subset of 37 maps with a balanced representation of RDoC domains constitute the training set, and the remaining held-out maps form the internal validation set. External validation is conducted using 36 peak coordinate …

Differences In Risk Appraisal And Neural Activity In Adolescents With A History Of Misconduct, Elizabeth S Escalante, Jessica S Flannery, Michael T Perino, Eva H Telzer

2020-Current year OA Pubs

While much of the prior work examining the behavioural and neural mechanisms of adolescent risk taking has focused on community samples, less is known about whether these mechanisms apply to adolescents engaging in high levels of risky behaviour. The current study examines behavioural and neural differences between adolescents with (N = 24) and without (N = 35) a history of misconduct using a risk perception questionnaire and risk-taking fMRI task. Adolescents with a history of misconduct perceived fewer negative consequences of risk relative to positive consequences and exhibited altered neural tracking of risk and reward in the nucleus accumbens. Specifically, …

Evolution Of The Umbilical Cord Blood Proteome Across Gestational Development, Leena B Mithal, Nicola Lancki, Ted Ling-Hu, Young Ah Goo, Sebastian Otero, Nathaniel J Rhodes, Byoung-Kyu Cho, William A Grobman, Judd F Hultquist, Denise Scholtens, Karen K Mestan, Patrick C Seed

2020-Current year OA Pubs

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 25 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. …

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Rachel M Presti, Et Al.

2020-Current year OA Pubs

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …

Utilizing Patient-Derived Xenografts To Model Precision Oncology For Biliary Tract Cancer, Timothy P Diperi, Kurt W Evans, Stephen Scott, Xiaofeng Zheng, Kaushik Varadarajan, Lawrence N Kwong, Michael Kahle, Hop S Tran Cao, Ching-Wei Tzeng, Thuy Vu, Sunhee Kim, Fei Su, Maria Gabriela Raso, Yasmeen Rizvi, Ming Zhao, Huamin Wang, Sunyoung S Lee, Timothy A Yap, Jordi Rodon, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Purpose: Biliary tract cancers, which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant biliary tract cancer models that recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in biliary tract cancers to create a resource for modeling precision oncology.

Experimental design: PDXs were derived from biliary tract cancer samples collected from surgical resections or metastatic biopsies. Alterations present in the PDXs were …

Pooled Safety Analysis And Management Of Sotorasib-Related Adverse Events In Kras G12c-Mutated Advanced Non-Small Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Maximilian Hochmair, Ramaswamy Govindan, Mark Vincent, Anthonie J Van Der Wekken, Noemi Reguart Aransay, Kenneth J O'Byrne, Nicolas Girard, Frank Griesinger, Makoto Nishio, Simon Häfliger, Colin Lindsay, Niels Reinmuth, Astrid Paulus, Pavlos Papakotoulas, Sang-We Kim, Carlos Gil Ferreira, Giulia Pasello, Michael Duruisseaux, Spyridon Gennatas, Anastasios Dimou, Bhakti Mehta, William Kormany, Chidozie Nduka, Brooke E Sylvester, Christine Ardito-Abraham, Yang Wang, Adrianus Johannes De Langen

Faculty, Staff and Student Publications

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; …

Clinical And Molecular Characteristics Of Patients With Brain Metastasis Secondary To Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Mark W Hurd, Abdelrahman Yousef, Ethan B Ludmir, Ashwathy B Pillai, Jennifer Peterson, Eugene J Koay, Sali Albarouki, Ching-Wei Tzeng, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Michael J Overman, Anirban Maitra, Shubham Pant, Brandon G Smaglo, Robert A Wolff, James Yao, John P Shen, Dan Zhao

Faculty, Staff and Student Publications

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed.

Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis …

A Qualitative Study On The Opportunities And Barriers Of Female Superintendents In The Northern Region Of Missouri, Rondalyn Vaughn

Student Theses and Dissertations

This qualitative phenomenological study aimed to explore the experiences of female superintendents in leadership positions, focusing on the opportunities and barriers they faced on the journey to the superintendency and in the position of superintendent. Women are underrepresented in the superintendency in the female-dominated educational field. The study examined the role of gender in leadership by identifying the barriers and opportunities women experienced along the path to the superintendency and in the superintendent position. Liberal Feminist Theory was adopted as a guiding framework, focusing on the effective practices, opportunities, and challenges faced by female superintendents. The liberal feminist theory was …

Rsk1 Is An Exploitable Dependency In Myeloproliferative Neoplasms And Secondary Acute Myeloid Leukemia, Tim Kong, Angelo B A Laranjeira, Christopher T Letson, Layow Yu, Shuyang Lin, Jared S Fowles, Daniel A C Fisher, Sherwin Ng, Wei Yang, Fan He, Jingxian Liu, Alexander B Kim, Maggie J Cox, Mary C Fulbright, Stacey L Rentschler, Li Ding, Grant A Challen, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation. Combining ATAC-Seq, CUT&Tag, RNA-seq, and CyTOF, we demonstrate that targeting of ribosomal protein S6 kinase A1 (RSK1) suppresses NFκB activation and diminishes pro-inflammatory mediators including tumor necrosis …

A Yeast-Based Oral Therapeutic Delivers Immune Checkpoint Inhibitors To Reduce Intestinal Tumor Burden, Olivia N Rebeck, Miranda J Wallace, Jerome Prusa, Jie Ning, Esse M Evbuomwan, Sunaina Rengarajan, Lemoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James Liao, Bejan Mahmud, Skye R S Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G Gorelik, Gautam Dantas, Et Al.

2020-Current year OA Pubs

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Improving Cooking Skills, Lifestyle Behaviors, And Clinical Outcomes For Adults At Risk For Cardiometabolic Disease: Protocol For A Randomized Teaching Kitchen Multisite Trial (Tk-Mt), Jennifer Massa, Candace Sapp, Kate Janisch, Mopelola A Adeyemo, Auden Mcclure, Natalia I Heredia, Deanna M Hoelscher, Tannaz Moin, Shaista Malik, Wendelin Slusser, David M Eisenberg

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.

METHODS: The intervention program includes 16 weeks of intensive hands-on culinary and lifestyle education classes followed by eight …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

Detection Of Elder Abuse Through Emergency Care Technicians Screening Tool Revision For Home-Based Primary Care (Detect-Rpc): A Cluster Randomised Controlled Trial Study Protocol, Brad Cannell, Nicholas Sevey, Melvin D Livingston, Jason Burnett, Kristin Lees Haggerty, Carolyn Pickering

Faculty, Staff and Student Publications

Introduction: The annual prevalence of elder mistreatment (EM) in cognitively intact older adults is estimated to be 11%, yet the annual prevalence in older adults with Alzheimer's disease and related dementias (AD/ADRD) is estimated to be as high as 75%. Associated with a decrease in quality of life and increase in risk of mortality, EM represents a significant public health burden. Home-based primary care (HBPC) providers are uniquely positioned to address the critical need for robust EM screening and reporting, especially among individuals with AD/ADRD. This protocol seeks to adapt the Detection of Elder mistreatment Through Emergency Care Technicians (DETECT) …

Engaging Dystonia Networks With Subthalamic Stimulation, Konstantin Butenko, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the same target. Therefore, a thorough investigation of neural substrates underlying stimulation effects on dystonia signs and symptoms is warranted. …

Sialylated Igg Induces The Transcription Factor Rest In Alveolar Macrophages To Protect Against Lung Inflammation And Severe Influenza Disease, Saborni Chakraborty, Derek E Byers, Philip A Mudd, Michael S Diamond, Et Al.

2020-Current year OA Pubs

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung …