Digital Commons Network^™

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Women's Preferences For Home-Based Self-Sampling Or Clinic-Based Testing For Cervical Cancer Screening, Joël Fokom Domgue, Monalisa Chandra, Olajumoke Oladoyin, Manali Desai, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Importance: While home-based self-sampling for cervical cancer screening is an evidence-based strategy proven to increase screening access and uptake, it is not currently recommended in the US despite recent Food and Drug Administration approval of the first at-home self-sampling device. Little nationally representative research has examined preference for and drivers of home-based self-sampling over clinic-based testing (the standard of care).

Objective: To assess women's perspectives about, reasons for considering, and factors associated with preferring at-home self-sampling for cervical cancer screening.

Design, setting, and participants: This population-based cross-sectional study used data from the 2024 Health Interview National Trends Survey (HINTS 7), …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Amyloidosis Of Bridging Veins Is A Pathologic Feature Of Alzheimer's Disease, Leon C D Smyth, Daan Verhaege, Elio Standen-Bloom, Yue Wu, Steffen E Storck, Pavle Boskovic, Benjamin A Plog, Tornike Mamuladze, Jose A Mazzitelli, Zhuoying Wang, Daniel D Lee, Gwendalyn J Randolph, Katherine E Schwetye, Song Hu, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by the accumulation of extracellular aggregated amyloid beta, resulting from impaired waste clearance. We recently identified new cerebrospinal fluid (CSF) efflux structures termed arachnoid cuff exit (ACE) points and speculated that these may be impacted in AD, leading to impaired waste clearance function. Using 5XFAD mice, we found progressive amyloidosis of bridging veins at ACE points. Indeed, in 5XFAD mice, there is impaired CSF efflux to the dura mater, impaired CSF flow along bridging veins, and impaired blood flow through bridging veins. These observations suggest that ACE point amyloidosis plays a role in waste clearance …

Estimated Effectiveness Of 2024-2025 Covid-19 Vaccination Against Severe Covid-19, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, …

Costs Of Single Maintenance And Reliever Therapy Vs Traditional Therapy For Asthma, Tri Pham, Abigail R Barker, Sarah A Eisenstein, Eliot Jost, Anna Volerman, Krutika Chauhan, Ross C Brownson, Timothy Mcbride, Mark D Huffman, Kaharu Sumino, Lynn B Gerald, Mario Castro, Anne E Dixon, James G Krings

2020-Current year OA Pubs

IMPORTANCE: Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption.

OBJECTIVE: To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of …

Demographic And Clinicopathologic Factors Associated With Colorectal Adenoma Recurrence, Usman Ayub Awan, Qingyuan Song, Kristen K Ciombor, Adetunji T Toriola, Jungyoon Choi, Timothy Su, Xiao-Ou Shu, Kamran Idrees, Kay M Washington, Wei Zheng, Wanqing Wen, Zhijun Yin, Xingyi Guo

2020-Current year OA Pubs

IMPORTANCE: Current colorectal surveillance guidelines emphasize adenoma characteristics but overlook temporal, racial, and sex-based heterogeneity in recurrence risk, a gap that limits equitable and personalized care.

OBJECTIVE: To evaluate the associations of demographic factors, obesity, and adenoma features with recurrence risk over time in a large longitudinal surveillance cohort.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adults who underwent their first colonoscopic polypectomy between January 1990 and July 2024 at a tertiary medical center.

EXPOSURES: Demographic variables included race and ethnicity, sex, obesity (body mass index >30), family history of colorectal cancer (CRC) or polyps, and age at …

Longitudinal Multiomic Signatures Of Ards And Sepsis Inflammatory Phenotypes Identify Pathways Associated With Mortality, Narges Alipanah-Lechner, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). …

Insomnia In Stimulant Use Disorders: Prevalence And Associations With Negative Affect, Isabella G Bourtin, Constanza De Dios, Jessica Vincent, Joy M Schmitz, Scott D Lane, Heather E Webber

Faculty, Staff and Student Publications

Research suggests that sleep disturbances are common among people who use psychostimulants, including cocaine use and methamphetamine use. These sleep disturbances hinder recovery, heighten relapse risk, and worsen physical and mental health outcomes. This study aimed to estimate the prevalence and severity of insomnia among individuals who use cocaine and methamphetamine and to explore potential psychological factors that are associated with more severe insomnia. The sample included participants who completed in-person screening assessments for ongoing studies at an outpatient research clinic. As a part of this screening, participants completed the Insomnia Severity Index (ISI) and validated assessments of psychological domains …

An Itpr1 Variant In The Ip3-Itpr1 Binding Pocket Associated With A Clinical Phenotype Of Athetoid Cerebral Palsy., Thania Ordaz, Jagadish Chandrabose Sundaramurthi, Adam S Arterbery, Anita M Bagley, Michael A Gargano, Jeremy P Bauer, Daniel Danis, Philip Giampietro, Ellen Raney, Lauren Rekerle, Mallory Shingle, Jon R Davids, Peter N Robinson

Faculty Research 2026

A de novo, missense variant in ITPR1-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), p.(Tyr567Cys), was identified by trio whole-genome sequencing in an individual diagnosed with Spinocerebellar ataxia 29 (SCA29) who was affected by cerebral palsy and global developmental delay. The variant affects a residue involved in Inositol 1,4,5-trisphosphate (IP3)-ITPR1 binding. Genotype-Phenotype correlation analysis of the set of missense variants affecting nine residues involved in IP3-ITPR1 binding in the current case and 170 reports of individuals with ITPR1 variants showed a significantly higher frequency of phenotypic features related to neurodevelopmental delay in these variants than in other ITPR1 variants. Our proband was …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Somatic Deficiency Of The Human E3 Ubiquitin Ligase Cbl In Leukocytes Impairs B Cell But Not T Cell Development And Function., Taja Vatovec, Anna-Lena Neehus, Katherine J L Jackson, Danielle T Avery, Ivan Bagarić, Lucia Erazo, Carlos A Arango-Franco, Masato Ogishi, Syed F Ahmed, Axel Cederholm, Amanda J Russell, Erika Della Mina, Dena Al-Rifai, Rowena Bull, Lori Buetow, Steicy Sobrino, Allison Zhang, Lara Wahlster, Marine Michelet, Nima Parvaneh, Jessica Peel, Federica Barzaghi, Davide Leardini, Quentin Philippot, Francesco Saettini, Jacques Dutrieux, Benedicte De Muylder, Francesca Vendemini, Francesco Baccelli, Albert Catala, Eleonora Gambineri, Marinella Veltroni, Vignesh Pandiarajan, Yurena Aguilar, Filomeen Haerynck, Michael Elliott, Stuart Turville, Fabienne Brillot, Taushif Khan, Filippo Consonni, Laureline Berteloot, William A Sewell, Geetha Rao, Laetitia Largeaud, Francesca Conti, Cecile Roullion, Cécile Masson, Francesco Pegoraro, Tianyi Ye, Samantha Joubran, Emily Villalpando, Boris Bessot, Yoann Seeleuthner, Tom Le Voyer, Jérémie Rosain, Hailun Li, Zarah Janda, Edoardo Muratore, Camille Soudée, Eric Delabesse, Claire Goulvestre, Mohammad Shahrooei, Anne Puel, Isabelle André, Christine Bole-Feysot, Laurent Abel, Miriam Erlacher, Vivien Béziat, Chantal Lagresle-Peyrou, Remi Cheynier, Emmanuelle Six, Nico Marr, Marlène Pasquet, Laia Alsina, Christopher C Goodnow, Nils Landegren, Alessandro Aiuti, Peng Zhang, Riccardo Masetti, Danny T Huang, Cindy S Ma, Jean-Laurent Casanova, Vijay G Sankaran, Jacinta Bustamante, Stuart G Tangye, Jonathan Bohlen

Faculty Research 2026

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Design And Implementation Of An Aapm Volunteer Database For Advancing Global Medical Physics Initiatives., Teh Lin, Minsun Kim, Courtney Morrison, Jiahan Zhang, Kevin Little, Yan-Hong Xin, Michael Woodward, Peter Sandwall, Eun Young Han

Oncology Articles

PURPOSE: The purpose of this study is to assess American Association of Physicists in Medicine (AAPM) members' availability to volunteer, share their expertise, and promote global collaboration in medical physics by partnering with international colleagues who seek support in strengthening their medical physics practice.

METHODS: The questionnaire was administered to AAPM members to assess their willingness to volunteer, preferred engagement modalities, and availability for different types of volunteer activities. The questionnaire was integrated into the AAPM member profile and covered therapy, diagnostic, and nuclear medicine disciplines, capturing participants' visiting preferences and expertise in teaching and training. Respondents were categorized based …

Obesity Does Not Significantly Impact Clinical Outcomes Following Anterior Cervical Discectomy And Fusion, Ishan Shah, Alejandro Perez-Albela, Riya Shah, Charles Furlong, Puru Sadh, John Czerwein, Alan Daniels, Bryce A Basques

SKMC Student Presentations and Publications

BACKGROUND: With obesity rates rising among patients undergoing anterior cervical discectomy and fusion (ACDF) and more procedures shifting to outpatient settings, this study aimed to evaluate the impact of body mass index (BMI) on complications, sagittal alignment, and patient-reported outcomes (PROs).

METHODS: A prospectively maintained database of 302 patients who underwent ACDF for myelopathy or radiculopathy between 2020 and 2022 at a single academic center was analyzed. Patients were stratified into four BMI categories: normal (18.5-< 25), overweight (25-< 30), obese class I (30-< 35), and obese class II/III (≥35). Collected data included demographics, comorbidities, perioperative variables, radiographic measures (cSVA, Cobb angle, etc.), and PROs (VAS, NDI). Univariate regression compared demographics, alignment, and PROs, while multivariate analyses assessed complications and perioperative factors.

RESULTS: BMI was not independently associated with higher rates of postoperative complications, including adjacent segment disease, subsidence, reoperation, or other adverse events. Patients in …

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …

Distribution Of Nematophagous Fungi And Soil-Transmitted Helminths In Outdoor Built Environments Across Latin America, Rojelio Mejia, Eva Mereles Aranda, Leticia Ojeda, Sandra Ocampos Benedetti, Janitzio J Guzman, Barton Slatko, Cristina Almazan, Melisa Diaz-Fernandez, Ruben Cimino, Marisa Juarez, Natalia Montellano Duran, Estefania Lorena Mansilla Flores, Paola Andrea Vargas, Amandeep Kaur, Nestor L Uzcategui, Lucia Estela Mejia, Katherine Elizabeth Keegan, Emilio Rey Mejia, Chiara Cássia Oliveira Amorim, Stefan M Geiger, Ricardo T Fujiwara, Luz Marina Llangarí-Arizo, Andrea Lopez, Natalia Romero-Sandoval, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

Background: Soil-transmitted helminths (STHs) are among the most common global parasitic infections, represent a significant worldwide public health burden, and remain a source of considerable morbidity in Latin America. Nematophagous fungi (NF), such as Arthrobotrys oligospora, naturally inhabit many soil types and are known for their ability to trap and kill nematodes using specialized hyphal structures or secreted enzymes and metabolites. As they prey on different developmental stages of helminths in soil, they may represent an ecological factor influencing helminth persistence and transmission dynamics.

Methods: Using an in vitro test, Toxocara cati eggs were exposed to A. oligospora. By using …

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Diagnostic Evaluation And Treatment Of Utis In Children With Neurogenic Bladder, Jacqueline G Holden, Sowdhamini Wallace, Pearl W Chang, Stephanie Davis-Rodriguez, Rana F Hamdy, John M Morrison, Michael J Tchou, Victor Trevisanut, Vijaya Vemulakonda, Catherine S Forster

Faculty, Staff and Students Publications

Objective: Children with neurogenic bladder (NGB) are at increased risk for urinary tract infections (UTIs), but there is a lack of guidelines to assist clinicians in diagnosing and treating these children. Our objective was to describe the presentation and treatment of provider diagnosed UTIs in children with NGB compared to children with vesicoureteral reflux (VUR) and to assess the proportion of children with NGB who met a consortium definition of UTI.

Study design: We included children < 18 years old with either VUR or NGB who were diagnosed in the emergency department with a febrile UTI in our multicenter retrospective cohort study. We extracted and compared UTI symptoms and urinalysis results specific to children with NGB to children with VUR. We measured the proportion of UTI diagnoses concordant with the Urologic Management to Preserve Initial Renal Function (UMPIRE) consensus definition of UTI, defined as ≥ 100,000 CFU/mL of 1 or 2 organisms, pyuria, and ≥ two symptoms of UTI.

Results: The most common symptom among all children in the cohort was vomiting (38.8 %). Of the 215 children with NGB, 41.3 % met …

Differential Longitudinal Effects Of Glucose-Lowering Medications On Glucagon And C-Peptide Responses In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Steven E Kahn, Mark Tripputi, John M Lachin, Ashok Balasubramanyam, Mary Ann Banerji, Joshua Barzilay, Robert M Cohen, W Timothy Garvey, Michaela R Gramzinski, Neda Rasouli, Mary Rhee, Jesse C Seegmiller, Vatsala Singh, William I Sivitz, Michael W Steffes, Kristina Utzschneider, Ralph A Defronzo

Faculty, Staff and Students Publications

Objective: To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.

Research design and methods: In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index [GGI]). Whether these measures and …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Prospective Evaluation Of The European Society Of Cardiology 0/1h-Algorithm’S Safety And Efficacy For Triage Of Patients With Suspected Myocardial Infarction (Presc1se-Mi): Rationale And Design Of A Prospective International Multicenter Stepped-Wedge Cluster Randomized Controlled Trial, Jasper Boeddinghaus, Paolo Bima, Luca Crisanti, Dagmar I Keller, Ksenija Slankamenac, Michael Christ, Philipp Schuetz, Andrea Wiencierz, Ivo Strebel, Julia Reinhardt, Iryna Vyshnevska, Tzu-Ying Tsao, Felix Mahfoud, Maria Pia Ruggieri, Stephan Steuer, Òscar Miró, Veli-Pekka Harjola, Fulvio Morello, Peiman Nazerian, Dominik Roth, José Luis Zamorano, Deborah Erica Gannon, Jason Pott, Mohammed Oa Abubakr, Hyun Suk Yang, Joe Young, Richina Bicette, Andreea Cuculici, Héctor Bueno, Juan Sanchis, Christian Mueller

Faculty, Staff and Students Publications

Background: International practice guidelines recommend the more rapid European Society of Cardiology (ESC) 0/1h-algorithm for the triage of patients with suspected myocardial infarction (MI) as the preferred option and consider the ESC 0/3h-algorithm as an alternative. However, many centers worldwide have not yet adopted the ESC 0/1h-algorithm in clinical practice due to uncertainty which approach best balances safety and efficacy.

Methods: PRESC1SE-MI (PRospective Evaluation of the European Society of Cardiology 0/1h-algorithm`s Safety and Efficacy for Triage of Patients with Suspected Myocardial Infarction) is an international, investigator-initiated multicenter, stepped-wedge, cluster randomized controlled trial. At least 52,156 consecutive adult patients with nontraumatic …

Training In Medications For Opioid Use Disorder And Buprenorphine Prescribing In The Post X-Waiver Era: Insights From A Nationwide, Multispecialty Survey, Sung In H Kim-Vences, Justin Nguyen, Jacqueline M Hirth, Kyle P Suen, Colleen A Keough, Roger Zoorob, Alicia A Kowalchuk

Faculty, Staff and Students Publications

Objective: The January 2023 repeal of the X-waiver aimed to reduce regulatory barriers to buprenorphine prescribing and enhance patient access to medications for opioid use disorder (MOUD). Its impact on prescribing by non-addiction-trained physicians, the integration of MOUD training into residency programs, and the role of mandated training on clinical practice remain unclear.

Methods: A 2024 online survey assessed physicians' awareness of the X-waiver repeal, exposure to MOUD training, and changes in buprenorphine prescribing. Multivariable logistic regression evaluated the independent effect of MOUD training and whether mandatory versus voluntary formats influenced prescribing behavior.

Results: Among 959 physicians (42.7 % residents), …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …