Digital Commons Network^™

Sleep Eeg And Respiratory Biomarkers Of Sudden Unexpected Death In Epilepsy (Sudep): A Case-Control Study, Oman Magana-Tellez, Rama Maganti, Norma J Hupp, Xi Luo, Sandhya Rani, Johnson P Hampson, Manuela Ochoa-Urrea, Sudha S Tallavajhula, Rup K Sainju, Daniel Friedman, Maromi Nei, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the most common category of epilepsy-related mortality. Centrally mediated respiratory dysfunction has been observed to lead to death in the majority of cases of SUDEP. SUDEP also mainly occurs during nighttime sleep. This study seeks to identify sleep EEG and sleep-related respiratory biomarkers of SUDEP risk.

Methods: In this case-control study, we compared demographic, clinical, EEG, and respiratory data from people with epilepsy who later died of SUDEP (the SUDEP group) with data from age and sex-matched living people with epilepsy, classified as high risk of SUDEP (with ≥1 generalised tonic-clonic seizure …

Wire-In-Needle Versus Conventional Syringe-On-Needle Technique For Ultrasound-Guided Central Venous Catheter Insertion In The Internal Jugular Vein: The Win Randomized Trial, Kristen K Thomsen, Jovana Stekovic, Felix Köster, Alina Bergholz, Karim Kouz, Moritz Flick, Daniel I Sessler, Christian Zöllner, Bernd Saugel, Leonie Schulte-Uentrop

Faculty, Staff and Student Publications

Purpose: There are different techniques for ultrasound-guided central venous catheter (CVC) insertion. When using the conventional syringe-on-needle technique, the syringe needs to be removed from the needle after venous puncture to pass the guidewire through the needle into the vein. When, alternatively, using the wire-in-needle technique, the needle is preloaded with the guidewire, and the guidewire-after venous puncture-is advanced into the vein under real-time ultrasound guidance. We tested the hypothesis that the wire-in-needle technique reduces the time to successful guidewire insertion in the internal jugular vein compared with the syringe-on-needle technique in adults.

Methods: We randomized 250 patients to the …

Continuous Versus Bolus Norepinephrine Administration And Arterial Blood Pressure Stability During Induction Of General Anaesthesia In High-Risk Noncardiac Surgery Patients: A Randomised Trial, Christina Vokuhl, Karim Kouz, Moritz Flick, Linda Krause, Alina Kröker, Parisa Moll-Khosrawi, Christian Zöllner, Daniel I Sessler, Bernd Saugel, Kristen K Thomsen

Faculty, Staff and Student Publications

Background: Hypotension after induction of general anaesthesia is common in high-risk patients having noncardiac surgery. Anaesthesiologists often give manual boluses of vasopressors repeatedly to maintain blood pressure during induction of general anaesthesia, including the fast-acting vasopressor norepinephrine which has a short half-life. We tested the hypothesis that giving norepinephrine continuously during induction of general anaesthesia, compared with giving it as repeated manual boluses, improves blood pressure stability in high-risk noncardiac surgery patients.

Methods: In this single-centre trial, 72 participants undergoing noncardiac surgery were randomised to continuous norepinephrine infusion or manual bolus norepinephrine administration during induction of general anaesthesia. Blood pressure …

Mitochondrial Haplogroups, But Not Heteroplasmy, Are Associated With Midlife Cognitive Function, Nien Yeh Daphne Yu, Shea J Andrews, Lifang Hou, Myriam Fornage, Kristine Yaffe

Faculty, Staff and Student Publications

Introduction: Mitochondrial DNA (mtDNA) variation may influence cognitive performance, but prior findings are inconsistent.

Methods: We analyzed data from 2308 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, assessing heteroplasmy (mtHz) burden and haplogroups (mtHg) from blood-derived mtDNA at three timepoints and cognitive function across multiple domains. Multivariate linear regression models and multivariate linear mixed models adjusted for age, sex, education, and race.

Results: MtDNA heteroplasmy burden and count were not associated with cognitive performance. However, mtHgs in macro-mtHg L were linked to poorer cognitive outcomes, particularly in processing speed and global cognition in cross-sectional and …

Development And Feasibility Testing Of An Implementation Evaluation Tool: Recommendations From The Managing Epilepsy Well (Mew) Network Research Collaborative, Martha Sajatovic, Ross Shegog, Elaine Kiriakopoulos, Clara Adeniyi, Jessie Black, Barbara C Jobst, Erica K Johnson, Robin Mcgee, Tanya M Spruill, Cam Escoffery

Faculty, Staff and Student Publications

Aims: The Managing Epilepsy Well (MEW) Network has led the development, testing and scale-up of epilepsy self-management (ESM). The MEW Integrated Database (MEW DB) is a pooled repository of archival studies that facilitates aggregate analysis. This report describes an implementation evaluation tool for ESM adopters.

Methods: Publicly available materials on program implementation, adoption and sustainability as well as readiness surveys used by the MEW Network were reviewed, as were content domains and format styles relevant to ESM implementation. Requirements for data Tiers included: 1) survey Tier should be short (≤6 items) and completed quickly (< 3 min), 2) question and response format should be consistent, 3) data elements are relevant to ESM adopters and 4) the tool should be applicable across ESM programs. Iterative review, discussion and item-ranking yielded a final set of 3 distinct data element Tiers.

Results: Implementation data elements assess …

Engaging And Empowering Future Female Surgeons: Development Of The Medical Student Section Of The Society Of Women In Urology, Allison G Booher, Sasha J Vereecken, Erin Kim, Neharika Penmatcha, Alexandra Aponte, Eman N Chaudhri, Meghana Noonavath, Ibukunoluwa Omole, Joanna Orzel, Leigh Martin, Gina Demeo, Tyler L Overholt, Akanksha Mehta

Faculty, Staff and Student Publications

Objective: To describe a replicable model for a large-scale, cross-institutional, and student-driven initiative to promote gender equity within surgical fields.

Methods: To address the lack of a national infrastructure to support female medical students pursuing careers in Urology, a historically male-dominated specialty, the society of women in urology (SWIU) established its medical student section, called SWIUdents, as a student-led initiative to offer mentorship, education, and networking resources for future female urologists. In 2022, SWIUdents convened its first medical student leadership board, comprised of two co-chairs and four subcommittees focused on membership, program implementation, mentorship, and community relations. SWIUdents membership was …

Three-Dimensional Human Mucopolysaccharidosis Iva Chondrocyte Culture Reveals Significant Impairments In The Lysosomal-Mitochondrial Crosstalk, Andrés Felipe Leal, Sampurna Saikia, Shaukat A. Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder (LSD) caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase enzyme. MPS IVA patients suffer from skeletal dysplasia due to the abnormal function of chondrocytes. Given the interactions of lysosomes with various intracellular organelles, it is not surprising that lysosomal dysfunction can lead to improper functioning of lysosome-interacting organelles such as mitochondria. Mitochondrial alterations have been evaluated in several LSDs; nevertheless, they have not been fully addressed in MPS IVA. In this study, we assessed the mitochondrial alterations in MPS IVA chondrocytes using a three-dimensional culture approach. Our findings revealed that MPS IVA …

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …

Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker

2020-Current year OA Pubs

IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.

OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.

EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …

Single-Cell And Bulk Transcriptome Analysis Identifies B-Cell Subpopulations And Associated Cancer Subtypes With Distinct Clinical And Molecular Characteristics, Yin He, Li Zhao, Yufen Zheng, Xiaosheng Wang

Faculty, Staff and Student Publications

Backgroud: Previous studies have identified B cell subpopulations with pro- and anti-tumoral activities, while the clinical relevance of B cell subpopulations-specific markers in pan-cancer remains understudied.

Methods: We integrated 14 scRNA-seq datasets (102,504 cells from 424 patients, 15 cancer types) to identify B cell subpopulations via unsupervised clustering. We characterized their functional dynamics and prognostic relevance through analyzing single-cell, bulk and spatial transcriptomic data. Moreover, using B cell subpopulations-specific gene signatures, we constructed models for predicting cancer prognosis and immunotherapy response.

Results: We identified eight B cell subpopulations (b00-b07) which were classified into naive, plasma, memory, germinal center (GC), and …

Factors Associated With Medication Adherence Among Patients With Attention-Deficit/Hyperactivity Disorder (Adhd), Linh Nguyen, Yen-Chi L Le, Hannah Reygaerts, Todd R Johnson, Cesar A Soutullo

Faculty, Staff and Student Publications

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common behavioral health condition that impacts 5% to 8% of children and 2.5% of adults worldwide. The symptoms of ADHD are effectively managed with medication, yet patients with ADHD may inconsistently take their medication. We assessed medication adherence among patients with ADHD and identified factors associated with medication adherence that may be utilized to optimize adherence.

Method: This is a retrospective, observational study among patients aged 4 years and older with a diagnosis of ADHD at primary care and multispecialty outpatient clinics during May 2021 to May 2023. We assessed sociodemographic characteristics, stratified by …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …

Design And Development Of An Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Human-Centered Design Approach, Kawtar Zouaidi, Jan Yeager, Suhasini Bangar, Sayali Tungare, Urvi Mehta, Janelle Urata, Alfa-Ibrahim Yansane, Thomas Tanbonliong, Jungsoo Kim, Emily Sedlock, Krishna Kumar Kookal, Yan Xiao, Tokede Oluwabunmi, Heiko Spallek, Amy Franklin, Gregory W Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: There are gaps in understanding the experiences of children, parents, and providers during dental conscious sedation. This study aimed to capture and analyze these experiences to identify opportunities for improvement and enhance the quality and safety of pediatric dental conscious sedation.

Methods: A human-centered design approach was used to examine the conscious sedation experience in 2 US advanced education pediatric dental clinics. Researchers conducted field observations, interviews with providers and parents, and providers focus groups to explore experiential factors. Data were transcribed and analyzed using content thematic analysis. Insights from the data were used to explore and generate new …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Morphometric Analysis Of Spina Bifida After Fetal Repair Shows New Subtypes With Associated Outcomes, L K Mann, S Pandiri, N Agarwal, H Northrup, K S Au, E Grundberg, E P Bergh, M T Austin, R Patel, B Miller, S Zhu, J S Feinberg, D Lai, K Tsao, S A Fletcher, R Papanna

Faculty, Staff and Student Publications

Objectives: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies. This study aimed to characterize types of spina bifida lesion and correlate them with preoperative presentation and postoperative outcome.

Methods: This was a secondary analysis of a prospective cohort of patients referred for fetal spina bifida who underwent fetoscopic repair between 2020 and 2023 at a single center. We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. The reproducibility of lesion classification was assessed using the Kappa …

Tirzepatide For The Maintenance Of Body Weight Reduction: Rationale, Design, And Baseline Characteristics Of Surmount-Maintain, Deborah B Horn, Louis J Aronne, Sean Wharton, Harold E Bays, Elisa Gomez-Valderas, Avigdor D Arad, Palash Sharma, Julia P Dunn, Cagri Senyucel, Clare J Lee

Faculty, Staff and Student Publications

Objective: SURMOUNT-MAINTAIN aims to evaluate the efficacy and safety of reducing the tirzepatide dose and/or continuing the maximum tolerated dose (MTD) versus placebo in maintaining body weight (BW) reduction achieved with tirzepatide MTD.

Methods: This Phase 3b, multicenter, randomized, parallel-arm, double-blinded, placebo-controlled, 52-week clinical trial is in progress comparing treatment with once weekly tirzepatide (5 mg and/or MTD of 15 mg or 10 mg) versus placebo in achieving BW reduction maintenance from the initial 60-week open-label weight-loss period on tirzepatide MTD, in adults with obesity (BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with ≥ 1 obesity-related comorbidity, excluding type …

Tofacitinib Ameliorates Campylobacter-Induced Intestinal Pathology By Suppressing Ifnγ Producing Ilcs And T Cells, Anna A Korchagina, Sergey A Shein, Wayne T Muraoka, Justin Nguyen, Qiangxing Chen, Anna A Tumanova, Austin W Todd, Carlos E Rivera, Rita Tamayo, Paolo Casali, Ekaterina Koroleva, Alexei V Tumanov

Faculty, Staff and Student Publications

Patients with autoimmune diseases are more susceptible to foodborne infections, which can be exacerbated by immunosuppressive therapy. Tofacitinib, a JAK/STAT pathway inhibitor, was recently approved for the treatment of ulcerative colitis, yet its effects on the pathogenesis of intestinal infections remain unclear. Here, we examined the impact of oral tofacitinib treatment in a mouse model of Campylobacter jejuni (C. jejuni) infection. Our results show that early tofacitinib administration attenuates intestinal pathology without affecting bacterial colonization. Specifically, tofacitinib suppressed CXCL1, CXCL2, CCL2 chemokine expression by intestinal epithelial cells, limiting recruitment of monocytes and neutrophils to the gut. In addition, JAK/STAT inhibition …

Family History Of Substance Use And Stressful Life Events Impact Adolescent Maturation Of Cerebral White Matter, Yizhou Ma, Ashley Acheson, Corneliu Bolbocean, Mustafa N Mithaiwala, Si Gao, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Xiaoming Du, A Ankeeta, Alia Warner, Antonio F Pagán, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Family history (FH) of substance use disorders (SUDs) and stressful life events (SLEs) are known risk factors for SUDs in adolescents and young adults. Cross‐sectional studies suggest that FH and SLEs affect adolescent white matter (WM) development and form abnormal WM patterns. Here, we examined the effects of FH, SLEs and their interaction on WM integrity in youths in the Adolescent Cognitive Brain Development (ABCD) study at baseline and 2‐ and 4‐year follow‐ups. ABCD youths (N = 8939, age ± SD = 9.9 ± 0.6 years, 4302 female) completed baseline diffusion tensor imaging, of which 5661 repeated the scan …

Community Firearm Violence And Dental Care Use In Middle Adulthood, Alexander Testa, Luis Mijares, Daniel Semenza, Richard Stansfield, Ian Silver, Dylan B Jackson, Ana Neumann, Jeff R Temple, Rahma Mungia

Faculty, Staff and Student Publications

Prior research links violence inside the home to reduced dental care utilization, yet little is known about how community firearm violence affects dental care behaviors. The current study used data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), linked to census tract-level fatal and nonfatal shooting data from the American Violence Project for the 100 largest cities in the United States. The analytic sample included 1925 respondents aged 33-42. The primary outcome was self-reported dental care use in the past year. Firearm violence exposure was categorized as 0, 1, or 2 + …

Nonprofit Hospital Ceo Compensation: Does Quality Matter?, Derek Jenkins, Marah Short, Vivian Ho

Faculty, Staff and Students Publications

Background: Past research has documented that increases in profits and health system size, as well as increases in the reward generosity for improving these metrics play an important role in explaining increases in nonprofit hospital CEO pay between 2012 and 2019.

Objectives: To test whether hospital quality measures play a supplemental role in determining CEO pay.

Research design: We estimated linear regressions for 2012 and 2019 of the log of CEO wages on system or independent hospital characteristics, including quality. The regressions were used to construct a Oaxaca decomposition of factors associated with CEO compensation.

Subjects: One thousand forty-seven nonprofit …

Lp(A) Testing For The Primary Prevention Of Cardiovascular Disease In High-Income Countries: A Cost-Effectiveness Analysis, Jedidiah I Morton, Florian Kronenberg, Magdalena Daccord, Nicola Bedlington, Marius Geanta, Tobias Silberzahn, Zhenyue Chen, Jean-Luc Eisele, Bogi Eliasen, Mariko Harada-Shiba, Marc Rijken, Albert Wiegman, George Thanassoulis, Pia R Kamstrup, Iñaki Gutierrez-Ibarluzea, Pablo Coral, Raul D Santos, Erik Stroes, Michal Vrablik, Gerald F Watts, Christie M Ballantyne, Samia Mora, Børge G Nordestgaard, Kausik K Ray, Stephen J Nicholls, Zanfina Ademi, Lp(A) International Taskforce (Itf) Initiative

Faculty, Staff and Students Publications

Background and aims: Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives.

Methods: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of …

Adeno-Associated Virus-Mediated Silencing Of Sox4 Leads To Long-Term Amelioration Of Liver Phenotypes In Mouse Models Of Alagille Syndrome, Duncan Fox, Jun Xie, Jennifer L Burwinkel, Josh M Adams, Kashish Chetal, Marzieh Keivandarian, Yaniv Faingelernt, Sanjay Subramanian, Mario F Lopez, Anna L Peters, Nathan Salomonis, Neda Zarrin-Khameh, Guangping Gao, Stacey S Huppert, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Background & aims: In patients with Alagille syndrome (ALGS), bile duct paucity often leads to severe cholestatic phenotypes for which liver transplantation remains the only definitive treatment. No Food and Drug Administration-approved mechanism-based strategies exist to enhance biliary development in ALGS or other diseases with bile duct paucity. We aimed to identify a therapeutic target to address this unmet need.

Methods: Preclinical ALGS mouse models lacking 1 copy of Jag1 with or without conditional deletion of 1 or both copies of Sox9 were used. Sox4 levels were reduced genetically or with adeno-associated virus 8 (AAV8) vectors driving a Sox4-silencing sequence. …

Phosphorylation At Serine 214 Correlates With Tau Seeding Activity In An Age-Dependent Manner In Two Mouse Models For Tauopathies And Is Required For Tau Transsynaptic Propagation, Pablo Martinez, Nur Jury-Garfe, Henika Patel, Yanwen You, Abigail Perkins, Yingjian You, Audrey Lee-Gosselin, Ruben Vidal, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Background

Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely understood.

Objective

To characterize the temporal dynamics of tau seeding activity and identify specific phosphorylated tau species associated with tau propagation in vivo.

Methods

We profiled tau seeding activity using a FRET-based biosensor cell line and correlated it with the abundance of phospho- and conformational tau species in two transgenic mouse models of tauopathy (P301S-1N4R and P301S-0N4R). Immunohistochemistry and subcellular fractionation were used to examine the spatial distribution of tau species. Functional …

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Tigit Affects Car Nk-Cell Effector Function In The Solid Tumor Microenvironment By Modulating Immune Synapse Strength, Ishwar Navin, Matthew Dysthe, Prashant S Menon, Corrine Baumgartner, Tim Sauer, Navin Varadarajan, Robin Parihar

Faculty, Staff and Students Publications

Therapies using NK cells that express chimeric antigen receptors (CAR-NK) have been successfully employed against hematologic malignancies. However, solid tumors resist CAR-NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has been implicated in impaired antitumor activity of endogenous NK cells, the consequences of TIGIT expression on engineered CAR-NKs have not been explored. To address this gap, we compared TIGIT-expressing and TIGIT-deleted human CAR-NKs targeting the GD2 solid tumor antigen in tumor immune microenvironment co-cultures and in vivo tumor immune …

Neck Pain In Migraine: A Narrative Review And Steps To Correct Evaluation And Treatment, Tayla A. Rees, Diana Doukhi, Victor S. Wang, Anita Balcerbula, Michelle Bravo, Haniyeh Fathi, Bahtigul Holmuratova, Michalis Kodounis, Seblewongel A. Seyoum, Semih Tasdelen, Hasmik Vekilyan, Edoardo Caronna, Patricia Pozo-Rosich

Department of Neurology Faculty Papers

Background: Neck pain is common in migraine patients, occurring during all migraine phases and between attacks. It can be a migraine symptom, trigger or a coexisting condition, and is associated with greater disability and poorer treatment response. There is evidence that neck pain associated with headaches can be frequently incorrectly diagnosed as a cervical disorder rather than migraine, resulting in a lack of appropriate treatment. Accurately assessing the connection between neck pain and migraine is crucial for effective treatment. Methods: This narrative review aims to summarise existing research on the role and contribution of neck pain in migraine, both as …

Examining The Relationship Between Dysphagia, Eating-Related Symptoms, And Diet Quality Among Oropharyngeal Cancer Patients During Critical Stages Of Cancer Survivorship: The U-Dine Study, Beatrice Manduchi, Vlad C Sandulache, Ji Yun Tark, Shreela Sharma, Ruosha Li, Emily Roller, Andrew Bevelhimer, Katherine A Hutcheson, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

Background: Diet quality is a modifiable factor impacting treatment outcomes in oropharyngeal cancer (OPC), yet the effect of dysphagia and self-reported eating-related symptoms remains unclear. This study examined their associations with diet quality in OPC patients.

Methods: A cross-sectional analysis was conducted with two parallel cohorts from MD Anderson Cancer Center and Michael E. DeBakey Veterans Affairs Medical Center as part of the Uncovering the Long-Term Impact of OPC and Dysphagia on Dietary Quality and Nutrition Among Cancer Survivors (U-DINE) Study. Participants at varying survivorship stages (prediagnosis, 3-6 and 18+ months posttreatment) were assessed for dysphagia (DIGEST scale) and six …

Nrf2 Hyperactivation As A Driver Of Radiotherapy Resistance And Suppressed Antitumor Immunity In Head And Neck Squamous Cell Carcinoma, Rutulkumar Patel, Kalil Saab, Lixia Luo, Yan Ma, Rashid Abdullah Osman, Nerissa T Williams, Jeffrey Everitt, Maciej J Zelazowski, Patricia Castro, William K Decker, William H Hudson, Jeffrey N Myers, Vlad C Sandulache, Mitchell J Frederick, Yvonne M Mowery, David G Kirsch

Faculty, Staff and Students Publications

Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ∼20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well studied.

Experimental design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed by Western …

Dysphoric Milk Ejection Reflex: Prevalence And Associations With Self-Reported Mental Health History, Megan Howard, Alison N Goulding, Anitha Muddana, Terri L Fletcher, Nicole Cirino, Alison M Stuebe

Faculty, Staff and Students Publications

This study sought to determine prevalence of Dysphoric Milk Ejection Reflex (D-MER) and mental health correlates in a cohort of patients from a breastfeeding medicine clinic. We determined prevalence of D-MER symptoms and performed bivariate analyses to explore associations between D-MER symptoms, demographics, and self-reported mental health history. Among 271 patients, 42 (15.5%) reported D-MER. Women with D-MER symptoms were more likely to report a history of panic attacks (28.6 vs. 12.2%, OR 2.87, 95% CI 1.23-6.25).