Digital Commons Network^™

Functional Performance Of Patients With Stroke During Inpatient Rehabilitation: A Cross-Sectional Study Of Home And Access Visits, Melissa J Krauss, Emily Somerville, Callista Poiter, Rebecca M Bollinger, Brianna M Holden, Gabrielle Blenden, Danielle Kretzer, Susan L Stark

2020-Current year OA Pubs

BACKGROUND: Home visits prior to inpatient rehabilitation facility (IRF) discharge allow occupational therapists to observe functional abilities among patients with stroke and address barriers that impact daily activities at home. However, home visits prior to IRF discharge are not standard practice due to barriers of time and cost constraints. We explored whether an access visit (visiting the home without the patient) could serve as an alternative to a home visit (with the patient) to anticipate functional abilities at home.

METHODS: We used baseline data from a randomized controlled trial that occurred before and during the COVID-19 pandemic, which caused predischarge …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

Faculty, Staff and Student Publications

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Myo5b And The Polygenic Landscape Of Very Early-Onset Inflammatory Bowel Disease In An Ethnically Diverse Population, Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer

Faculty, Staff and Students Publications

Background: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.

Methods: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored …

Plural Molecular And Cellular Mechanisms Of Pore Domain, Timothy J Abreo, Emma C Thompson, Anuraag Madabushi, Kristen L Park, Heun Soh, Nissi Varghese, Carlos G Vanoye, Kristen Springer, Jim Johnson, Scotty Sims, Zhigang Ji, Ana G Chavez, Miranda J Jankovic, Bereket Habte, Aamir R Zuberi, Cathleen M Lutz, Zhao Wang, Vaishnav Krishnan, Lisa Dudler, Stephanie Einsele-Scholz, Jeffrey L Noebels, Alfred L George, Atul Maheshwari, Anastasios Tzingounis, Edward C Cooper

Faculty, Staff and Students Publications

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. Kcnq2G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

2020-Current year OA Pubs

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Automated Breast Density Assessment For Full-Field Digital Mammography And Digital Breast Tomosynthesis, Shu Jiang, Debbie L Bennett, Simin Chen, Adetunji T Toriola, Graham A Colditz

2020-Current year OA Pubs

Mammographic density is a strong risk factor for breast cancer and is reported clinically as part of Breast Imaging Reporting and Data System (BI-RADS) results issued by radiologists. Automated assessment of density is needed that can be used for both full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) as both types of exams are acquired in standard clinical practice. We trained a deep learning model to automate the estimation of BI-RADS density from a prospective Washington University clinic-based cohort of 9,714 women, entering into the cohort in 2013 with follow-up through October 31, 2020. The cohort included 27% non-Hispanic …

Opaque Ontology: Neuroimaging Classification Of Icd-10 Diagnostic Groups In The Uk Biobank, Ty Easley, Xiaoke Luo, Kayla Hannon, Petra Lenzini, Janine Bijsterbosch

2020-Current year OA Pubs

BACKGROUND: The use of machine learning to classify diagnostic cases versus controls defined based on diagnostic ontologies such as the International Classification of Diseases, Tenth Revision (ICD-10) from neuroimaging features is now commonplace across a wide range of diagnostic fields. However, transdiagnostic comparisons of such classifications are lacking. Such transdiagnostic comparisons are important to establish the specificity of classification models, set benchmarks, and assess the value of diagnostic ontologies.

RESULTS: We investigated case-control classification accuracy in 17 different ICD-10 diagnostic groups from Chapter V (mental and behavioral disorders) and Chapter VI (diseases of the nervous system) using data from the …

Buprenorphine And Postpartum Contraception Utilization Among People With Opioid Use Disorder: A Multi-State Analysis, Kevin Y Xu, Jennifer K Bello, Joanna Buss, Hendrée E Jones, Laura J Bierut, Dustin Stwalley, Hannah S Szlyk, Caitlin E Martin, Jeannie C Kelly, Ebony B Carter, Elizabeth E Krans, Richard A Grucza

2020-Current year OA Pubs

BACKGROUND: The postpartum period provides an opportunity for birthing people with opioid use disorder (OUD) to consider their future reproductive health goals. However, the relationship between the use of medication for opioid use disorder (MOUD) and contraception utilization is not well understood. We used multistate administrative claims data to compare contraception utilization rates among postpartum people with OUD initiating buprenorphine (BUP) versus no medication (psychosocial services receipt without MOUD (PSY)) in the United States (US).

METHODS: In this retrospective cohort study, we analyzed data from the Merative™ MarketScan

RESULTS: Our sample consisted of 11,118 postpartum people with OUD. Among those, …

The Impact Of Covid-19 On Hiv Care: A Comprehensive Analysis Of Patient And Healthcare Providers Experiences At The Largest Hiv Treatment Center In Ghana, Peter Puplampu, Justice K Baah, Karl Osei Afoduo, Bright A Adjei, Araba Abaidoo-Myles, Victor G Davila-Roman, George B Kyei, Collins S Ahorlu

2020-Current year OA Pubs

BACKGROUND: We sought to determine how the COVID-19 pandemic affected care delivery for HIV patients in Ghana.

METHODS: Guided by the Consolidated Framework for Implementation Research (CFIR), we performed a cross-sectional study between May and July 2021 among 40 people living with HIV and 19 healthcare providers caring for HIV patients. In-depth interviews and focus group discussions were done with HIV patients, doctors, nurses, pharmacists, laboratory scientists, data scientists, administrators, and counselors to ascertain barriers and facilitators to HIV care during the pandemic. We asked for their input on removing barriers to care during this and future pandemics. Data was …

Couple-Based Lifestyle Intervention For Minority Prostate Cancer Survivors: A Randomized Feasibility Trial, Dalnim Cho, Yisheng Li, Karen Basen-Engquist, Chiara Acquati, Nga T T Nguyen, Hilary Ma, Curtis A Pettaway, Lorna H Mcneill

Faculty, Staff and Student Publications

Background: Black and Hispanic prostate cancer (PCa) survivors, who face a high burden of comorbid conditions and often engage in low levels of physical activity and healthy eating, remain significantly underrepresented in lifestyle intervention studies.

Purpose: Given the significance of spousal influence, we developed a culturally tailored lifestyle intervention for these survivors and their spouses and assessed its feasibility, acceptability, and impact on behavioral change.

Methods: Survivor-spouse couples were randomly assigned to an intervention group (n = 22), which received 12 health-coaching calls over 6 months, or a usual-care control group (n = 9). Assessments were conducted at baseline (T1), …

Early Treatment Discontinuation In Patients With Deficient Mismatch Repair Or Microsatellite Instability High Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD).

Methods: To assess whether ETD is associated with similar outcomes compared …

Us Military Veterans’ Perceived Concordance With Their Providers Regarding Persistent Physical Symptoms Prospectively Predicts Satisfaction With Care And Adherence To Care Plans, L Alison Phillips, Laura M Lesnewich, Katharine Bloeser, Yong Lin, Rachel L Boska, Justeen K Hyde, Peter J Bayley, Helena K Chandler, Matthew J Reinhard, Susan L Santos, Rachel Stewart, Drew A Helmer, Lisa M Mcandrew

Center for Medical Ethics and Health Policy Staff Publications

Background: Medically unexplained, persistent physical symptoms and syndromes are commonly seen in primary care. These are debilitating for patients and difficult to treat, causing frustration for patients and providers.

Purpose: This study investigates how well US military veterans with multiple persistent physical symptoms (PPS), called Gulf War illness (GWI), agree with their healthcare providers about their illness. This agreement, called perceived concordance, is hypothesized to influence veterans' satisfaction with care, adherence to care plans, and disability levels.

Methods: Participants were 230 veterans with GWI deployed to the 1990-1991 Gulf War who were recruited from Veteran Affairs primary care and War …

Integrative Multiomics Reveals Common Endotypes Across Psen1, Psen2, And App Mutations In Familial Alzheimer's Disease, Phoebe Valdes, Andrew B Caldwell, Qing Liu, Michael Q Fitzgerald, Srinivasan Ramachandran, Celeste M Karch, Dominantly Inherited Alzheimer Network (Dian), Douglas R Galasko, Shauna H Yuan, Steven L Wagner, Shankar Subramaniam

2020-Current year OA Pubs

BACKGROUND: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

METHODS: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1

RESULTS: We identified common disease endotypes, such as dedifferentiation, dysregulation of synaptic signaling, repression of mitochondrial function and metabolism, and inflammation. …

A Prospective, Multicenter Analysis Of The Integrated 31-Gene Expression Profile Test For Sentinel Lymph Node Biopsy (I31-Gep For Slnb) Test Demonstrates Reduced Number Of Unnecessary Slnbs In Patients With Cutaneous Melanoma., J Michael Guenther, Andrew Ward, Brian J Martin, Mark Cripe, Rohit Sharma, Stanley P Leong, Joseph I Clark, John Hamner, Timothy Beard

Oncology Articles

BACKGROUND: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with <  5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

METHODS: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322). To determine if incorporating the i31-GEP into decision-making resulted in fewer SLNBs performed, propensity score-matching was performed to a non-overlapping cohort for whom the 31-GEP was not used for SLNB decision-making.

RESULTS: No patients with <  5% i31-GEP predicted risk had a positive SLNB (0/35). Propensity matching demonstrated an 18.5% reduction in SLNBs performed (43.7% vs. 62.2%. p <  0.001). The i31-GEP could have reduced the number of unnecessary biopsies by 25.0% (35/140).

CONCLUSIONS: This prospective study confirmed the performance and clinical utility of the i31-GEP for …

Rethinking The Rise Of Early-Onset Gastrointestinal Cancers: A Call To Action, Benjamin A Weinberg, Caitlin C Murphy, David R Freyer, K Leigh Greathouse, Jan K Blancato, Elena M Stoffel, Julia L Drewes, Anne Blaes, John M Salsman, Y Nancy You, Hannah Arem, Reetu Mukherji, Priyanka Kanth, Xin Hu, Anne Fabrizio, Marion L Hartley, Marios Giannakis, John L Marshall

Faculty, Staff and Student Publications

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship …

Mate-Pair Sequencing Enables Identification And Delineation Of Balanced And Unbalanced Structural Variants In Prenatal Cytogenomic Diagnostics, Jicheng Qian, Huilin Wang, Hailei Liang, Yuting Zheng, Mingyang Yu, Wing Ting Tse, Angel Hoi Wan Kwan, Lo Wong, Natalie Kwun Long Wong, Isabella Yi Man Wah, So Ling Lau, Shuk Yi Annie Hui, Matthew Hoi Kin Chau, Xiaoyan Chen, Rui Zhang, Liona C Poon, Tak Yeung Leung, Pengfei Liu, Kwong Wai Choy, Zirui Dong

Faculty, Staff and Students Publications

Background: Mate-pair sequencing detects both balanced and unbalanced structural variants (SVs) and simultaneously informs in relation to both genomic location and orientation of SVs for enhanced variant classification and clinical interpretation, while chromosomal microarray analysis (CMA) only reports deletion/duplication. Herein, we evaluated its diagnostic utility in a prospective back-to-back prenatal comparative study with CMA.

Methods: From October 2021 to September 2023, 426 fetuses with ultrasound anomalies were prospectively recruited for mate-pair sequencing and CMA in parallel for prenatal genetic diagnosis. Balanced/unbalanced SVs and regions with absence of heterozygosity (AOH) were detected and classified independently, and comparisons were made between mate-pair …

Rapid Viral Suppression Using Integrase Inhibitors During Acute Hiv-1 Infection, Mehri S Mckellar, Jessica R Keys, Lindsey M Filiatreau, Kara S Mcgee, Joann D Kuruc, Guido Ferrari, David M Margolis, Joseph J Eron, Charles B Hicks, Cynthia L Gay

2020-Current year OA Pubs

BACKGROUND: Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.

METHODS: This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

RESULTS: Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics …

Multiparametric Mri Along With Machine Learning Predicts Prognosis And Treatment Response In Pediatric Low-Grade Glioma, Anahita Fathi Kazerooni, Adam Kraya, Komal Rathi, Meen Chul Kim, Arastoo Vossough, Nastaran Khalili, Ariana Familiar, Deep Gandhi, Neda Khalili, Varun Kesherwani, Debanjan Haldar, Hannah Anderson, Run Jin, Aria Mahtabfar, Sina Bagheri, Yiran Guo, Qi Li, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R Lueder, Saksham Phul, Mateusz Koptyra, Phillip Storm, Jeffrey Ware, Yuanquan Song, Christos Davatzikos, Jessica Foster, Sabine Mueller, Michael J Fisher, Adam Resnick, Ali Nabavizadeh

Department of Neurosurgery Faculty Papers

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free …

Covid-19 Vaccine Hesitancy Among Black Women In The Us, Brittany C Slatton, Farrah G Cambrice, Serwaa S Omowale

Faculty, Staff and Student Publications

IMPORTANCE: COVID-19 vaccine hesitancy among Black women is a critical public health concern, potentially exacerbating existing health disparities and impacting community-wide vaccination efforts.

OBJECTIVE: To explore the factors associated with COVID-19 vaccine hesitancy among Black women in the US and identify the specific concerns and experiences shaping hesitant attitudes toward vaccination.

DESIGN, SETTING, AND PARTICIPANTS: Qualitative study using in-depth, semistructured interviews conducted virtually between June and November 2021. Thematic analysis was used to identify key themes from the interview data. Participants were recruited through social media platforms and word-of-mouth referrals from various regions of the US. Interviews were conducted remotely …

Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski

Faculty, Staff and Student Publications

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned …

Adverse Prehospital Events And Outcomes After Traumatic Brain Injury, Amelia W Maiga, Hsing-Hua Sylvia Lin, Stephen R Wisniewski, Joshua B Brown, Ernest E Moore, Martin A Schreiber, Bellal Joseph, Chad T Wilson, Bryan A Cotton, Daniel G Ostermayer, Brian G Harbrecht, Mayur B Patel, Jason L Sperry, Francis X Guyette, Henry E Wang

Faculty, Staff and Student Publications

Importance: While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes.

Objective: To validate the associations of prehospital hypoxia, hypotension, and hypocarbia with TBI outcomes in a US national trauma network.

Design, setting, and participants: This cohort study examined data from 8 level I trauma centers and their affiliated ground and air emergency medical services (EMS) agencies in the Linking Investigations in Trauma and Emergency Services (LITES) Network from January 1, 2017, to June 30, 2021. Adult patients …

The Role Of Iowa Gambling Task Performance In Response To Citalopram Treatment For Cocaine Use Disorder, Constanza De Dios, Robert Suchting, Charles E Green, Heather E Webber, F Gerard Moeller, Scott D Lane, Joy Schmitz

Faculty, Staff and Student Publications

Background:

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use.

Objectives:

The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Methods:

We conducted a secondary analysis of a double-blind, placebo-controlled, randomized Bayesian adaptive trial investigating citalopram efficacy in CUD treatment-seeking adults. At baseline and mid-treatment, participants completed assessments of decision-making (Iowa Gambling Task; IGT), attention, response inhibition, and cognitive flexibility. Outcomes were longest duration of abstinence (LDA; count of consecutive …

Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 …

Cardiovascular Disease And Breast Cancer Stage At Diagnosi\S, Ivan Angelov, Allen M Haas, Elizabeth Brock, Lingfeng Luo, Jing Zhao, Benjamin D Smith, Sharon H Giordano, Nicholas J Leeper, Kevin T Nead

Faculty, Staff and Student Publications

Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.

Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.

Design, setting, and participants: This population-based case-control study used data from the Surveillance, Epidemiology, and End Results-Medicare linked databases from 2009 to 2020. The analysis was completed from May 2023 to August 2024. Participants were …

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …

Covid-19 Pandemic And Racial And Ethnic Disparities In Long-Term Nursing Home Stay Or Death Following Hospital Discharge, Laurent G Glance, Karen E Joynt Maddox, Patricia W Stone, Jingjing Shang, E Yoko Furuya, Ashley M Chastain, Ji Won Lee, Bridget Morse-Karzen, Andrew W Dick

2020-Current year OA Pubs

IMPORTANCE: Long-term nursing home stay or death (long-term NH stay or death), defined as new long-term residence in a nursing home or death following hospital discharge, is an important patient-centered outcome.

OBJECTIVE: To examine whether the COVID-19 pandemic was associated with changes in long-term NH stay or death among older adults with sepsis, and whether these changes were greater in individuals from racial and ethnic minoritized groups.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used patient-level data from the Medicare Provider Analysis and Review File, the Master Beneficiary Summary File, and the Minimum Data Set. Community-dwelling individuals aged at least …

Utility Of Candidate Genes From An Algorithm Designed To Predict Genetic Risk For Opioid Use Disorder, Christal N Davis, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

OBJECTIVE: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study examined the association of 15 candidate genetic variants with risk of OUD using electronic health record data from December 20, 1992, to September 30, 2022. Electronic health record …

Delivering Guideline-Concordant Care For Patients With High-Risk Hpv And Normal Cytologic Findings, Jasmin A Tiro, Jacquelyn M Lykken, Patricia M Chen, Cheryl R Clark, Sarah Kobrin, Jessica Chubak, Sarah Feldman, Claudia Werner, Steven J Atlas, Michelle I Silver, Jennifer S Haas

2020-Current year OA Pubs

IMPORTANCE: As US health care systems shift to human papillomavirus (HPV)-based cervical cancer screening, more patients are receiving positive high-risk non-16/18 genotype HPV results and negative for intraepithelial lesion or malignancy (NILM) cytological findings. Risk-based management guidelines recommend 2 consecutive negative annual results to return to routine screening.

OBJECTIVE: To quantify patterns of surveillance testing and associated outcomes for patients after an HPV-positive results and NILM cytologic findings.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed patients in the METRICS (Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings and Populations) cohort of the PROSPR II (Population-Based Research …

Brain Age Modeling And Cognitive Outcomes In Young Adults With And Without Sickle Cell Anemia, Andria L Ford, Slim Fellah, Yan Wang, Kira Unger-Levinson, Maria Hagan, Martin N Reis, Amy Mirro, Josiah B Lewis, Chunwei Ying, Kristin P Guilliams, Melanie E Fields, Hongyu An, Allison A King, Yasheng Chen

2020-Current year OA Pubs

IMPORTANCE: Both sickle cell anemia (SCA) and socioeconomic status have been associated with altered brain structure and cognitive disability, yet precise mechanisms underlying these associations are unclear.

OBJECTIVE: To determine whether brains of individuals with and without SCA appear older than chronological age and if brain age modeling using brain age gap (BAG) can estimate cognitive outcomes and mediate the association of socioeconomic status and disease with these outcomes.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of 230 adults with and without SCA, individuals underwent brain magnetic resonance imaging (MRI) and cognitive assessment. Brain age was estimated using DeepBrainNet, …

A Single-Cell Compendium Of Human Cerebrospinal Fluid Identifies Disease-Associated Immune Cell Populations, Claudia Cantoni, Roman A. Smirnov, Maria Firulyova, Prabhakar S. Andhey, Tara R. Bradstreet, Ekaterina Esaulova, Marina Terekhova, Elizabeth A. Schwarzkopf, Nada M. Abdalla, Maksim Kleverov, Anne H. Cross, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Et Al.

2020-Current year OA Pubs

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, …