Digital Commons Network^™

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …

Irx2 And Nptx1 Differential Regulation Of Β-Catenin Underlies Mek-Mediated Proliferation In Human Neuroglial Cells, Alexander Chen, Hannah Wang, Xuanwei Li, Corina Anastasaki, David H Gutmann

2020-Current year OA Pubs

The two major genomic alterations in pediatric pilocytic astrocytoma (PA) are

Estimated Burden Of Coccidioidomycosis, Samantha L Williams, Andrej Spec, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Coccidioidomycosis is an underrecognized fungal infection that can cause serious illness and constitutes a considerable public health burden. The number of cases is likely substantially higher than the nationally reported total, as surveillance does not capture patients who do not seek medical care or who are undiagnosed or misdiagnosed. Coccidioidomycosis is not reportable in all states, and cases not reported to public health entities are likewise missed. A systematic estimate of coccidioidomycosis burden is needed to raise awareness and inform public health interventions and policy.

OBJECTIVE: To assess the annual burden of symptomatic coccidioidomycosis in the US.

DESIGN, SETTING, …

Phenotypic Expansion Of Knobloch Syndrome Type 2 In An Individual With A De Novo Pak2 Variant., Elizabeth A Werren, Louisa Kalsner, Jessica M Ewald, Michael Peracchio, Cameron King, Purva Vats, Peter A Audano, Peter N Robinson, Mark D Adams, Melissa A Kelly, Adam P Matson

Faculty Research 2025

P21-activated kinase 2 (PAK2) is a serine/threonine kinase essential for a variety of cellular processes including signal transduction, cellular survival, proliferation, and migration. A recent report proposed monoallelic PAK2 variants cause Knobloch syndrome type 2 (KNO2)-a developmental disorder primarily characterized by ocular anomalies. Here, we identified a novel de novo heterozygous missense variant in PAK2, NM_002577.4:c.1273G>A, p.(D425N), by genome sequencing in an individual with features consistent with KNO2. Notable clinical phenotypes observed in this individual were global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, failure to thrive, pyloric stenosis, feeding intolerance, patent ductus arteriosus, and mild facial …

Workplace Perk Or Pitfall? A Qualitative Study Of Genetic Counselors' Perspectives And Experiences With Workplace Genetic Testing., Elizabeth Charnysh, Katherine Hendy, Kerry Ryan, Anya E R Prince, W Gregory Feero, Alyx Vogle, Sarah Mccain, Alexandra Truhlar, J Scott Roberts, Charles Lee, Kunal Sanghavi, Wendy R Uhlmann, The Insight @ Work Consortium

Faculty Research 2025

Some employers offer genetic testing for increased cancer and cardiovascular disease risk, as well as pharmacogenetic variants, as a wellness benefit, which presents unique considerations for genetic counseling. Our ethical, legal, and social implications (ELSI) of genomics study, positioned in a post-positivist paradigm, aimed to qualitatively assess the perspectives and experiences of genetic counselors (GCs) who had counseled on workplace genetic testing (wGT). Semi-structured interviews were conducted with 18 US GCs who either worked in the wGT industry (i.e., role-directed wGT experience) or provided post-test counseling in a clinical setting (i.e., patient-directed wGT experience). Interviews were analyzed following the principles …

Placental And Cord Blood Dna Methylation Changes Associated With Gestational Diabetes Mellitus In A Marginalized Population: The Untold Role Of Saturated Fats., Fatima Ahmad, Sidra Aftab Uzair, Arun P Lakshmanan, Shaikha Alabduljabbar, Salma H Ahmed, Basirudeen Syed Ahamed Kabeer, Alexandra Katharina Marr, Tomoshige Kino, Tobias Brummaier, Rose Mcgready, François Nosten, Damien Chaussabel, Souhaila Al Khodor, Annalisa Terranegra

Faculty Research 2025

The role of DNA methylation (DNAm) and its modulation by dietary factors in gestational diabetes mellitus (GDM) remains underexplored, particularly in marginalized populations. This study investigates DNAm alterations in GDM-exposed cord blood and placenta and their association with maternal dietary quality and single nutrient intake in a low-income population from the Myanmar-Thailand border. A matched case-control design (GDM: n = 38, controls: n = 34) was selected from a Myanmar-Thailand pregnancy cohort. Dietary intake was assessed via 24-h recalls and analyzed using Nutritionist Pro, with dietary quality evaluated by the healthy eating index (HEI). DNAm was profiled in 72 cord …

Understanding And Addressing Mental Health Challenges Of Families Admitted To The Neonatal Intensive Care Unit., Ashley D. Osborne, Daphna Yasova Barbeau, Tiffany Gladdis, Kara Hansen, Tonia Branche, Emily R. Miller, Christine C. Pazandak, Margaret K. Hoge, Michelle Spencer, Diana Montoya-Williams, Ryan Barbeau, Heather Padratzik, Stephen Lassen

Manuscripts, Articles, Book Chapters and Other Papers

This article reviews the psychological distress experienced by NICU families, including anxiety, postpartum depression (PPD), and post-traumatic stress disorder (PTSD), in addition to providing recommendations for clinicians at the individual, institutional, and national level. Currently, mental health screenings, specialized evaluations, and treatment options are not routinely offered to NICU families and are frequently under-utilized when offered. Here we provide expert opinion recommendations to address challenges in supporting universal screening, offering bedside interventions, including trained mental health professionals in care plans, updating neonatology training competencies, and advocating for policies that support the mental health of NICU families. We advocate that mental …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Norovirus Replication, Host Interactions And Vaccine Advances, B V Venkataram Prasad, Robert L Atmar, Sasirekha Ramani, Timothy Palzkill, Yongcheng Song, Sue E Crawford, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus …

Neuroanatomical Features Of Naa10 And Naa15-Related Neurodevelopmental Syndromes, Rahi Patel, Rikhil Makwana, Carolina Christ, Elaine Marchi, Christina Y Miyake, Fabricio Guimaraes Goncalves, Gholson J Lyon, Matthew T Whitehead

Faculty, Staff and Students Publications

Background: NAA10-related and NAA15-related neurodevelopmental (ND) syndromes present with intellectual disability, hypotonia, cardiac abnormalities, and delayed development. While data exists on the clinical manifestations of these conditions, there are few reports describing the neuroanatomical abnormalities present on imaging.

Objective: We aim to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess the severity and number of neuroanatomical anomalies and their associated functional impairments to better understand the pathophysiology of these disease processes.

Materials and methods: Neuroimaging studies were obtained from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in …

Large-Scale Plasma Proteomic Profiling Unveils Diagnostic Biomarkers And Pathways For Alzheimer’S Disease, Gyujin Heo, Ying Xu, Erming Wang, Muhammad Ali, Hamilton Se-Hwee Oh, Patricia Moran-Losada, Federica Anastasi, Armand González Escalante, Raquel Puerta, Soomin Song, Jigyasha Timsina, Menghan Liu, Daniel Western, Katherine Gong, Yike Chen, Pat Kohlfeld, Allison Flynn, Alvin G Thomas, Joseph Lowery, John C Morris, David M Holtzman, Joel S Perlmutter, Suzanne E Schindler, Natalia Vilor-Tejedor, Marc Suárez-Calvet, Pablo García-González, Marta Marquié, Maria Victoria Fernández, Mercè Boada, Amanda Cano, Agustín Ruiz, Bin Zhang, David A Bennett, Tammie Benzinger, Tony Wyss-Coray, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer's disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to identify new proteins, pathways and predictive models for AD. We identified 416 proteins (294 new) associated with clinical AD status and validated the findings in two external datasets representing more than 7,000 samples. AD-related proteins reflected blood-brain barrier disruption and other processes implicated in AD, such as lipid dysregulation or immune responses. A machine learning model was used to identify a set …

Identification And Functional Assessment Of Candidate Causal Cis-Regulatory Variants Underlying Electrocardiographic Qt Interval Gwas Loci, Supraja Kadagandla, Lavanya Gunamalai, Dongwon Lee, Ashish Kapoor

The Brown Foundation: Institute of Molecular Medicine

Background: Identifying causal variants among tens or hundreds of associated variants at each locus in genome-wide association studies is challenging. As the vast majority of genome-wide association studies variants are noncoding, sequence variation at cis-regulatory elements (CREs) affecting transcriptional expression of specific genes is a widely accepted molecular hypothesis. Following this hypothesis, combined with the observation that open chromatin is a universal hallmark of all types of CREs, we aimed to identify candidate causal cis-regulatory variants underlying QT interval genome-wide association studies loci.

Methods: Common variants in high linkage disequilibrium with genome-wide significant variants were identified using variant …

Understanding Utilization And Prevention Measures Associated With A Caries Risk Assessment In Oral Health Transformation, Melody Mcgee, Ryan Brandon, Muhammad Walji, Joel White, Kristen Moses, Eric P Tranby, Lisa J Heaton, Kristen Simmons

Faculty, Staff and Student Publications

Objectives: Dental decay is endemic in the United States, underscoring the need to measure the utilization of caries risk management tools to elucidate the effect of prevention interventions in reducing the dental decay rates of individuals. An academic institution partnered with a third-party institute to call attention to the utilization and prevention measures associated with caries risk assessment (CRA) used with children 0-18 years. This environmental scan examined claims across the United States to evaluate the proportion of dental examinations, CRAs, and caries prevention procedures within a calendar year.

Methods: A 12-month deidentified participant list categorized by age, race, sex, …

Factors Associated With Perceived Medication Safety During Transitions Of Care In Patients With Cancer: A Secondary Data Analysis Of A Cross-Sectional Survey, Youmin Cho, Misun Hwang, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: This study aimed to investigate perceived medication safety in patients with cancer during transitions of care and identify factors associated with their safety perceptions.

Methods: A secondary data analysis was performed on a cross-sectional survey data of from patients with four types of cancer (i.e., colorectal, lung, prostate, and breast). Perceived medication safety was measured by the sum score of four survey items that assessed patients' feelings about medication safety during transitions of care. Potential associated factors included sociodemographic and clinical factors (i.e., cancer types, taking oral anticancer agents), self-rated health, perceived safety in communicating with clinicians, beliefs about …

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …

Multicancer Early Detection Tests At A Crossroads: Commercial Availability Ahead Of Definitive Evidence, Carmen E Guerra, Jennifer Keating Litton, Carolina E Viswanath, A Mark Fendrick

Faculty, Staff and Student Publications

Multicancer early detection tests (MCEDs), sometimes referred to as liquid biopsies, are tests that can screen for multiple cancers by analyzing blood, urine, and other bodily fluids for biomarkers released by cancer cells. These tests have the potential to change the cancer screening paradigm if they are shown to reduce cancer mortality. However, it is not yet known whether MCEDs reduce mortality. Randomized controlled trials, the gold standard for evaluating cancer screening programs, are currently evaluating the effectiveness of MCEDs. However, because cancer-specific and all-cause mortality are end points that can take years to reach, trials are being designed with …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Aapm Task Group No 249b-Essentials And Guidelines For Clinical Medical Physics Residency Training Programs, Jonathon A Nye, Joseph P Dugas, William D Erwin, David P Gierga, Darryl G Kaurin, Stephanie M Leon, Ho-Ling Anthony Liu, Zheng Feng Lu, Alphonso W Magri, Lynn N Rill, Leah K Schubert, Beth A Schueler, Irina Vergalasova, John Vetter, Brian D Wichman, Amy Shu-Jung Yu, Dandan Zheng

Faculty, Staff and Student Publications

The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document …

Functional Vs Structural Cortical Deficit Pattern Biomarkers For Major Depressive Disorder, Peter Kochunov, Bhim M Adhikari, David Keator, Daniel Amen, Si Gao, Nicole R Karcher, Demetrio Labate, Robert Azencott, Yewen Huang, Hussain Syed, Hongjie Ke, Paul M Thompson, Danny J J Wang, Braxton D Mitchell, Jessica A Turner, Theo G M Van Erp, Neda Jahanshad, Yizhou Ma, Xiaoming Du, William Burroughs, Shuo Chen, Tianzhou Ma, Jair C Soares, L Elliot Hong

Faculty, Staff and Student Publications

Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

Objective: To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus …

Multi-Institutional Study On Image Quality For A Novel Cbct Solution On O-Ring Linac, Luis Agulles-Pedrós, R Lee Macdonald, Amanda Jean Cherpak, Nayha Dixit, Lei Dong, Tianyu Zhao, Kundan Thind, Anthony Doemer, Boon-Keng Teo, Shiqin Su, Alexander Moncion, James L Robar

Faculty, Staff and Student Publications

INTRODUCTION: This work presents a multi-institutional study on image quality provided by a novel cone beam computed tomography (CBCT). The main goal is to investigate the consistency of imaging performance across multiple institutions.

METHODS: Phantoms for measuring relative electron density (RED) and image quality were sent to six institutions for imaging on Ethos and Halcyon units equipped with HyperSight CBCT. The imaging protocols included tube potential from 100 to 140 kVp and exposure from 80 to 800 mAs. Imaging performance was evaluated with regard to RED versus Hounsfield units (HU), uniformity, contrast-to-noise ratio (CNR), slice thickness, circular symmetry, modulation transfer …

Gsk-3484862, A Dnmt1 Degrader, Promotes Dnmt3b Expression In Lung Cancer Cells, Qin Chen, Swanand Hardikar, Kimie Kondo, Nan Dai, Ivan R Corrêa Jr, Meigen Yu, Marcos R Estecio, Xing Zhang, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques, Jumah G Ahmad, Alexander J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

International Multidisciplinary Consensus Recommendations On Clinical Application Of Three-Dimensional Visualization In Precision Surgery For Pediatric Liver Tumors, Qian Dong, Wenli Xiu, Benjie Tang, Eiso Hiyama, Mary T Austin, Yeming Wu, Xiaojun Yuan, Chengzhan Zhu, Chengli Liu, Hiroki Ishibashi, Karthik K Tappa, Huanmin Wang, Chuandong Sun, Yuntao Ma, Hongwei Xi, Jian Wang, Jianghua Zhan, Kyong Ihn, Mitsuo Shimada, Mingman Zhang, Mary E Brindle, Patrick B Thomas, Shigehisa Fumino, Tao Liu, Thom Lobe, Udo Rolle, Shan Wang, Xiaowen Zhai, Yoshinori Koga, Yoshiaki Kinoshita, Yuzuo Bai, Zhaozhu Li, Zhe Wen, Weikang Pan, Krysta M Sutyak, Pier C Giulianotti

Faculty, Staff and Student Publications

Background: Pediatric liver tumors are predominantly primary malignant tumors, and complete tumor resection with sufficient preservation of liver tissue is crucial for improving prognosis. However, due to the delicate anatomical structure of the pediatric liver and the relatively large size of the tumors, especially in difficult cases, the surgical challenges are substantial. While precision liver surgery are widely applied in clinical practice, pediatric cases require more customized approaches. The application of three-dimensional (3D) visualization technology is crucial for enhancing surgical accuracy, allowing for precise preoperative planning and intraoperative guidance.

Methods: This consensus was collaboratively developed by 36 experts from eight …

Utility Of Revised Risk Analysis Index As A Predictor Of Mortality And Morbidity In Orthopaedic Trauma., Chirag Soni, Victor Koltenyuk, Nithin Gupta, Haad A Arif, Aruni Areti, Taylor Manes, Luke A Lopas, Jan P Szatkowski, Christian A Bowers, Benjamin C Taylor, Jack W Weick

Trauma and Acute Care Articles

OBJECTIVES: The aim of this study was to determine the applicability of the Revised Risk Analysis Index (RAI-Rev) in orthopaedic trauma and compare the predictive discrimination for the RAI-Rev and the 5-Item Modified Frailty Index (mFI-5) for 30-day postoperative outcomes.

DESIGN: This is a retrospective cohort study.

SETTING: The American College of Surgeons National Surgical Quality Improvement database was used.

PATIENT SELECTION: All patients aged 18 or older who underwent surgical treatment for forearm, humerus, pelvis, acetabulum, femur, tibia, and hindfoot fractures from 2015 to 2020 were included.

OUTCOME: 30-day postoperative mortality, major complications, and wound complications consisting of surgical …

Gut Microbiota In Immuno-Oncology: A Practical Guide For Medical Oncologists With A Focus On Antibiotics Stewardship, Arielle Elkrief, Bertrand Routy, Lisa Derosa, Laura Bolte, Jennifer A Wargo, Jennifer L Mcquade, Laurence Zitvogel

Faculty, Staff and Student Publications

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the …