Digital Commons Network^™

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Automated Quantification Of Movement Qualities In The Human Upper Extremity After Stroke Using A Wearable Robot., Yoon No Gregory Hong, Kyoungsoon Kim, Sheng Li, Marcia K O'Malley, Ashish D Deshpande, Jinsook Roh

Faculty, Staff and Student Publications

Background: Stroke is a leading cause of long-term adult disability, with approximately 80% of survivors experiencing upper extremity (UE) motor impairments. Conventional tools like the Fugl-Meyer Assessment (FMA) are widely used but limited by ordinal scales and subjective visual observation. While wearable robotics offer high-resolution data, their clinical translation is hindered by a lack of standardized protocols and limited interpretability for clinical decision-making.

Objective: This study aimed to develop an objective, standardized, and clinically interpretable method to quantify UE motor qualities by integrating wearable robotic technology with traditional clinical assessment tasks.

Methods: Ten healthy individuals and ten stroke survivors performed …

Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage

Faculty, Staff and Students Publications

Forensic human identification relies on length-based differences in short tandem repeats (STRs) across autosomal and Y chromosomes, which require separate reactions and provide limited resolution. While next-generation sequencing offers greater discriminatory power, most platforms are expensive and restricted to traditional lab settings. Nanopore sequencing has the potential to change this with the real-time, portable MinION sequencer. However, forensic-specific tools that generate STR profiles compatible with established length-based databases are lacking. To address this, we developed STRspy2.0, which simultaneously profiles autosomal and Y-STRs using nanopore reads. STRspy2.0 produced accurate profiles for 54 multiplexed control libraries and 41 mock casework samples (blood, …

Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli

Faculty, Staff and Student Publications

Background: Protection of telomere 1 (POT1) tumor predisposition syndrome (POT1-TPD) is a hereditary leukemia syndrome that is identified in ∼5% of patients with chronic lymphocytic leukemia (CLL) and is characterized by a predisposition to other cancers, including gliomas, melanomas, and angiosarcomas. This study reports clinical and genetic characteristics of a large cohort of individuals with POT1-TPD.

Materials and methods: Individuals with pathogenic/likely pathogenic germline POT1 variants referred to the Hereditary Hematologic Malignancy Clinic at The University of Texas MD Anderson Cancer Center were included. Individuals with variants of uncertain significance were included if found to have telomeres >90th percentile of …

Control Arm Overperformance In Phase 3 Oncology Clinical Trials, Ansel P Nalin, Pavlos Msaouel, Adam J Grippin, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Noah S Meimoun, Ethan B Ludmir, Alexander D Sherry

Faculty, Staff and Student Publications

Background: In randomized clinical trials (RCTs), anticipating control arm outcomes is important for power calculations and enrollment goals. Unexpected overperformance of the control arm can underpower RCTs. The objective of this study was to estimate the prevalence of control arm overperformance in phase 3 oncology RCTs.

Methods: The authors conducted a meta-epidemiological study of two-arm, superiority-design, phase 3 oncology RCTs. They reviewed articles/publications and protocols for power calculations, justification, and outcomes. Control arm performance was measured as the ratio of observed control arm outcomes relative to pretrial estimates, and overperformance was defined as a 10% improvement.

Results: In total, 385 …

Common Serum Biomarkers And Combination Ratios In The Diagnosis Of Periprosthetic Joint Infection Following Total Hip Arthroplasty, Jason M Dayan, Don H Le, Anzar Sarfraz, Theodor Di Pauli Von Treuheim, Farouk Khury, Sallie Yassin, Vinay K Aggarwal, Ran Schwarzkopf, Alan J Dayan

Faculty, Staff and Student Publications

Accurate preoperative diagnosis of periprosthetic joint infection (PJI) is difficult, complicating distinction between septic and aseptic failures. This study assessed the value of common serum biomarkers and three calculated ratios-albumin-globulin ratio (AGR), C-reactive protein-albumin ratio (CAR), and C-reactive protein-AGR ratio (CAGR)-in diagnosing PJI after primary total hip arthroplasty (THA). We retrospectively reviewed patients undergoing revision THA for PJI or aseptic failure from 2011 to 2021 at a single institution. Inclusion required reported serum white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin (Alb), and total protein (TP). Diagnostic performance was evaluated using areas under the curve …

First Detection Of Xylazine In Texas Wastewater And Its Association With Fentanyl Use, Katherine M Joseph, Xuan Qin, Dhvani Parikh, Feng Li, John Balliew, Kristina D Mena, Fuqing Wu

Faculty, Staff and Students Publications

Xylazine is a veterinary sedative increasingly found in the U.S. illicit drug supply and is a growing public health concern due to its association with overdose events. To investigate its spatial distribution and relationship with fentanyl use, we analyzed 124 wastewater samples from four treatment plants serving the City of El Paso, Texas, over 13 months (June 2023 to July 2024) using liquid chromatography tandem mass spectrometry. Xylazine detections varied across sewersheds, with detection rates of 29.0%, 12.9%, 9.7%, and 0% and peak loads of 110±40 μg/day/1000 people. Norfentanyl (a primary fentanyl metabolite) was detected in all samples (100%), reaching …

Primary Tumor Size And Tumor-Vessel Interface Following Capecitabine And Temozolomide For Pancreatic Neuroendocrine Tumor, Jin Guo, Kever A Lewis, Laura Prakash, Priya Bhosale, Ajaykumar Morani, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Rebecca Snyder, Michael P Kim, Chandrikha Chandrasekharan, Arvind Dasari, James C Yao, Jeffrey E Lee, Jessica E Maxwell, Daniel M Halperin

Faculty, Staff and Student Publications

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …

Weight Loss Patterns And Clinical Outcomes Of Glp1 Receptor Agonists In Breast Cancer Survivors, Jasmine S Sukumar, Akshara Singareeka Raghavendra, Sarah Pasyar, Roland L Bassett, Debu Tripathy, Carlos H Barcenas, Karen M Basen-Engquist, Banu K Arun

Faculty, Staff and Student Publications

Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 - 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free …

What Did We Learn About Vads In 2024-2025?, Maya Guglin

The VAD Journal

This is our 11th annual literature review on left ventricular assist devices (LVADs). Our previous reports were well received by readers.^1-10 In prior years, we also included other forms of mechanical circulatory support (MCS); however, this year, we present a separate review focused exclusively on temporary MCS.

In this article, we summarize the most interesting, from our standpoint, publications from 2024 and 2025, with some inclusion of late 2023 studies that were initially released online before print. For the first time, we provide an independent review on short-term MSC devices, including the intra-aortic balloon pump, Impella (Abiomed), and extracorporeal …

“My Heart Was In My Stomach”: Texas-Based Obstetricians’ And Gynecologists’ Experiences Post Anti-Abortion Legislation, Chelsey Kanipe, Precious Chiamaka Anunobi, Anupria D Davenport, Sheryl A Mccurdy, Marie A Brault

Faculty, Staff and Student Publications

Background

The purpose of this study is to investigate the downstream effects of anti-abortion legislation on the practice of obstetrics and gynecology in urban Texas.

Methods

We conducted semi-structured interviews until saturation with eleven obstetricians/gynecologists (OBGYNs) to explore the effects of Texas’s abortion laws. Analysis consisted of inductive and deductive approaches.

Results

We identified three main themes regarding the downstream effects of Texas abortion laws: the conflicting role of colleagues as a support system and a source of frustration and distrust for OBGYNs, the lowered standard of care for those with a desired pregnancy, and concerns that anti-abortion legislation will …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

Three-Dimensional Versus Two-Dimensional Echocardiographic Assessment Of Left Atrial Volume And Deformation In Children, Alexander J Kiener, James Croft, Krista N Harris, Ankona Banerjee, Aura A Sanchez, Xander H T Wehrens, Anitha Parthiban, Xiaotian Gao, Tam T Doan, Minh B Nguyen

Faculty, Staff and Students Publications

Background: Left atrial (LA) volume and function are important for assessing pediatric diastolic dysfunction (DD). Three-dimensional echocardiographic (3DE) LA assessment may overcome limitations and assumptions inherent in two-dimensional echocardiographic (2DE).

Methods: We conducted a cross-sectional study of children under 18 years of age with structurally normal hearts, using transthoracic 3DE apical volume datasets. LA volumetric function and phasic deformation analyses were performed using 3DE (GE, EchoPAC 4DLAQ v206, near fully-automated) and 2DE (TomTec, TTA2.51, CPA, manual) was performed by three operators and processing time was collected. Agreement and reproducibility was assessment for each modality.

Results: Fifty patients (median age 12.8 …

A Framework For Assessing The Trustworthiness Of Scientific Research Findings, Brian A Nosek, David B Allison, Kathleen Hall Jamieson, Marcia Mcnutt, A Beau Nielsen, Susan M Wolf

Children’s Nutrition Research Center Staff Publications

Vigorous debate has erupted over the trustworthiness of scientific research findings in a number of domains. The question "what makes research findings trustworthy?" elicits different answers depending on whether the emphasis is on research integrity and ethics, research methods, transparency, inclusion, assessment and peer review, or scholarly communication. Each provides partial insight. We offer a systems approach that focuses on whether the research is accountable, evaluable, well-formulated, has been evaluated, controls for bias, reduces error, and whether the claims are warranted by the evidence. We tie each of these components to measurable indicators of trustworthiness for evaluating the research itself, …

Performance Of An Automated Sleep Scoring Approach For Actigraphy Data In Children And Adolescents, Pin-Wei Chen, Erica C Jansen, Christopher M Cielo, Ariel A Williamson, Margaret Banker, Michael Kaye, Peter X K Song, Karen E Peterson, Alejandra Cantoral, Martha María Téllez-Rojo, Cathy Goldstein, Khadija Zanna, Akane Sano, Jennette P Moreno, Heidi Kalkwarf, Babette S Zemel, Jonathan A Mitchell

Children’s Nutrition Research Center Staff Publications

Study objectives: GGIR is an R package for processing raw acceleration data to estimate sleep health parameters. We aimed to (1) assess the performance of three sleep algorithms within GGIR against PSG for detecting sleep/wake in clinically referred, typically-developing children (criterion validity); and (2) describe GGIR-derived sleep estimates from typically developing children enrolled in multiple cohort studies (face validity).

Methods: For criterion evaluation, children (8-16 years, N = 30) wore an actigraphy device for one night during in-lab polysomnography with performance assessed using epoch-by-epoch analyses. For face validity evaluation, four community/free living datasets were used: (1) Bone Mineral Accretion in …

Trends In County-Level Childhood Vaccination Exemptions In The Us, Mustafa Fattah, Lauren A Stoffel, Kate M Bubar, Samantha J Bents, Yvonne Maldonado, Peter J Hotez, Mathew V Kiang, Nathan C Lo

Faculty, Staff and Students Publications

This study examines US county-level trends in nonmedical and medical exemptions to childhood vaccination requirements.

Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley

Faculty, Staff and Students Publications

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance …

Multimodal Spatial-Omics Reveal Co-Evolution Of Alveolar Progenitors And Proinflammatory Niches In Progression Of Lung Precursor Lesions, Fuduan Peng, Ansam Sinjab, Yibo Dai, Warapen Treekitkarnmongkol, Sujuan Yang, Lorena I Gomez Bolanos, Tieling Zhou, Minyue Chen, Alejandra G Serrano, Avantika Krishna, Nastaran Karimi, Manvi Sharma, Akshay Basi, Guangsheng Pei, Jianlong Liao, Yunhe Liu, Jiping Feng, Zahraa Rahal, Yang Liu, Jiahui Jiang, Kai Yu, Tala Noun, Yuejiang Liu, Khaja Khan, Kyung Serk Cho, Jichao Chen, Luisa M Solis, Sarah Mazzilli, Steven Dubinett, Tina Cascone, Avrum E Spira, Stephen Swisher, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Tomoo Itoh, Takashi Yao, Kenji Suzuki, Neda Kalhor, Ignacio I Wistuba, Mingyao Li, Seyed Javad Moghaddam, Junya Fujimoto, Jared Burks, Jeffrey Myers, Kadir Akdemir, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are …

High-Throughput Multi-Organ Proteomics Workflow For Drug Efficacy And Toxicity Analysis, Yun Xiong, Lin Tan, Wai-Kin Chan, Dandan Zhu, Huimin Zhang, Eric S Yin, Sri Ramya Donepudi, Jibin Ding, Bo Wei, Bao Tran, Sara Martinez, Iqbal Mahmud, Faiza Hanif Waghu, Hamish I Stewart, Daniel J Hermanson, Rehan Akbani, John N Weinstein, Junjie Chen, Philip L Lorenzi

Faculty, Staff and Student Publications

Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present a high-throughput mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively. As a practical application, we analyzed 507 samples composed of 13 different tissues from mice treated with the enzyme-drug L-asparaginase (ASNase) or its glutaminase-free Q59L mutant, generating a quantitative profile of 11,472 proteins following drug treatment. The MS …

Familial History Of Aortic Disease Does Not Affect Outcomes Of Fenestrated-Branched Endovascular Aortic Repair In Patients With Complex Aortic Aneurysms, Aidin Baghbani, Safa Savadi, Titia A L Sulzer, Emanuel R Tenorio, Thomas Mesnard, Andrea Vacirca, Bernardo C Mendes, Naveed U Saqib, Steven Maximus, Ying Huang, Gustavo S Oderich

Faculty, Staff and Student Publications

Purpose: Familial history of aortic disease has been associated with increased risk of aneurysm-related complications after standard endovascular aortic repair. The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) for complex aortic aneurysms in patients with or without familial aortic aneurysms (FAAs).

Materials and methods: We reviewed the clinical data of consecutive patients enrolled in a prospective non-randomized study to investigate outcomes after FB-EVAR for treatment of complex aortic aneurysms between 2013 and 2022. Familial aortic aneurysm was defined as occurrence of an aortic aneurysm or dissections in a first- or second-degree relative and …

Discovery And Characterization Of A Novel Pseudomonas Phage Of A New Genus, Paul Nicholls, Justin R Clark, Anthony Maresso

Faculty, Staff and Students Publications

Background: Bacteriophages exhibit great diversity and are classically divided into lytic and temperate lifestyles. Commonly, bioinformatics is used to predict the temperate lifestyle. As the nosocomial pathogen Pseudomonas aeruginosa is common in freshwater, this biome represents an ideal location for the discovery of Pseudomonas phages.

Materials and methods: We characterized a genetically distinct species of Pseudomonas phage using next-generation sequencing and conventional microbiological methods. We characterized its lifestyle by purifying infected colonies and identifying persistent phage production.

Results: Genetics revealed a phage of a novel genus. Characterization showed a narrow host range and bioinformatics suggested a lytic lifestyle. Experimental data …

Impaired Arginine, Citrulline And Glutamine Metabolism In Type 2 Diabetes: Insights From A Stable Isotope Study, Mustafa Tosur, Raven A Wierzchowska-Mcnew, Nicolaas E P Deutz, Mariëlle P K J Engelen

Children’s Nutrition Research Center Staff Publications

Context: Arginine (Arg) is an important amino acid in T2D as a potent insulin secretagogue and precursor for nitric oxide (NO). Citrulline (Cit), the substrate for de novo Arg synthesis, is mostly produced from glutamine (Gln).

Objective: We aimed to investigate their metabolism in T2D using novel stable isotope tracer approach.

Methods: We studied 42 individuals (21 with T2D, 21 controls). After overnight fasting, blood samples were collected following pulse administration of stable amino acid tracers. Plasma concentrations and isotopic enrichments were measured by LC-MS/MS, and compartmental analyses were performed to calculate their whole-body production (WBP) rates and kinetics.

Results: …

Artificial Intelligence In Medical Ethics Education: A Descriptive Study Of Eight Models In Multiple Choice Question Generation, John Obeid, Christopher Bobier, Alex Gillham, Adam Omelianchuk, Daniel Hurst

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Integrating artificial intelligence (AI) into medical education poses barriers and opportunities for medical educators. One of those opportunities is content creation for medical ethics assessment. Assessing the performance of AI in generating multiple choice questions (MCQs) in ethics that aligns with United States Medical Licensing Examination (USMLE) is important. The present study evaluates the performance of eight AI models-GPT-4 Turbo, GPT-3.5 Turbo 0125, o1 Mini, o1 Preview, GPT-4, Claude 3.5 Sonnet, Claude 3 Opus, and Gemini-in regard to the relevance, clarity, and accuracy of generated ethics-based MCQs.

Methods: Each of the eight models was tasked with generating two sets …

The Use Of Storytelling In Covid-19 Vaccine Promotion: A Scoping Review Of Interventions And Campaigns, Suha Ballout, Sabreen A Darwish, Patricia J Kelly, Teresa Keller, Ross Shegog, Basil H Aboul-Enein

Faculty, Staff and Student Publications

Background: The development of the COVID-19 vaccine, a groundbreaking scientific advancement, also fueled vaccine hesitancy mainly due to vaccine misinformation and the limited public understanding of the new technology and its rapid pace of development and deployment. A variety of public health communication strategies have been used that include engaging the community in identifying and developing messages, using culturally appropriate communication methods, applying behavioral health principles, and storytelling. The purpose of this scoping review was to assess the most relevant evidence from the research literature on storytelling interventions to mitigate COVID vaccine hesitancy during the pandemic.

Methods: A scoping review …

Genome And Transcriptome-Wide Analyses Identify Multiple Candidate Genes And A Significant Polygenic Contribution In Bicuspid Aortic Valve, Sébastien Thériault, Jacob A Holdcraft, Dinara Sharipova, Adèle Faucherre, Radoslaw M Debiec, Gina M Peloso, Baravan Al-Kassou, Sary Aranki, Elena Ashikhmina Swan, Andrea Ballotta, Michele Bellino, Hanna M Björck, Anne Sophie Boureau, Peter S Braund, François Corriveau, François Dagenais, Lasse Folkersen, Amalia Forte, Michael D Francke, Alessandro Frigiola, Svetlana Gorbatov, Dongchuan Guo, Karam M Habchi, Mahyar Heydarpour, Eric M Isselbacher, Chris Jopling, Fabien Laporte, Solena Le Scouarnec, Zhonglin Li, Peter Lichtner, Carlo Maj, Hasanga D Manikpurage, Christopher P Nelson, Thy B Nguyen, Russell A Norris, Chin Siang Ong, Philippe Pibarot, Tanmoy Roychowdhury, Berardo Sarubbi, Floriane Simonet, Thoralf Sundt, Ida Surakka, Idit Tessler, Cristen J Willer, Susanne Wittmann, Bo Yang, Igor Berezovets, Stefanie A Doppler, Martina Dreßen, Katharina Knoll, Thomas Puehler, Heribert Schunkert, Jean-François Avierinos, Malenka M Bissell, Aidan P Bolger, Yohan Bossé, Eduardo Bossone, María Brion, Rodolfo Citro, Carlo De Vincentiis, G Michael Deeb, Alessandro Della Corte, Christian Dina, Ronen Durst, Stephan Ensminger, Per Eriksson, Arturo Evangelista, Anders Franco-Cereceda, Dan Gilon, Betti Giusti, Simon L Hetherington, Gordon S Huggins, Markus Krane, Thierry Le Tourneau, Giuseppe Limongelli, Patrick Mathieu, David Messika-Zeitoun, Hector I Michelena, Dianna Milewicz, Jochen D Muehlschlegel, David R Murdock, Georg Nickenig, Stefano Nistri, Markus M Nöthen, Francesca Pluchinotta, Siddharth K Prakash, Nilesh J Samani, Jean-Jacques Schott, Tom R Webb, Stéphane Zaffran, Salim Abdelilah-Seyfried, Kim Eagle, Johannes Schumacher, Teresa Trenkwalder, Simon Body

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.

Methods: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified …

Tracking Focal Adhesion Turnover: A Novel Reporter For Fa-Phagy Flux, Kuizhi Qu, Mengjun Dai, Ying Jiang, Sophie Liu, John P Hagan, Louise D Mccullough, Zhen Xu, Yan-Ning Rui

Faculty, Staff and Student Publications

Focal adhesions (FAs) are critical multi-protein complexes regulating cell adhesion, migration, and survival, and their dysregulation contributes to cancer metastasis and vascular diseases. Despite extensive research on FA formation, little is known about FA turnover, particularly its regulation by autophagy. This study introduces a novel tandem fluorescence reporter capable of tracking the entire FA-phagy flux, from autophagosome formation to lysosomal degradation. The reporter, based on a red–green fluorescence system with a lysosome-specific cleavage site, integrates seamlessly into endogenous focal adhesion complexes, demonstrating sensitivity and specificity to autophagy stimuli. Validated in multiple cell lines, the tool revealed dynamic FA-phagy responses to …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler

Faculty, Staff and Students Publications

Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.

Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.

Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …