Digital Commons Network^™

Differences In Patient And Parent Preferences For Prognostic Communication Across Disease Milestones In Advanced Childhood Cancer, Rachel A Kentor, Shoshana Mehler, Caroline Christianson, Harmony Farner, Tara M Brinkman, Justin N Baker, Pamela S Hinds, Jennifer W Mack, Erica C Kaye

Faculty, Staff and Students Publications

Background: Navigating prognostic communication is challenging for clinicians caring for adolescents and young adults (AYAs) with poor-prognosis cancer. Presently, little is known about how AYA and parent preferences for prognostic disclosure evolve over time. This study explored communication preferences at key illness milestones of disease progression to inform individualized, person-centered approaches to optimize prognostic disclosure.

Procedure: Sixty-five participants, including 25 AYAs aged 12-25 years and 40 parents, were recruited at distinct illness timepoints-diagnosis, relapse/progression, Phase I/II trial enrollment, and bereavement-to participate in semi-structured interviews about their preferences for timing, style, and content of prognostic communication. Rapid analysis was conducted to …

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

Coco-St Detects Global And Local Biological Structures In Spatial Transcriptomics Datasets, Muhammad Aminu, Bo Zhu, Natalie Vokes, Hong Chen, Lingzhi Hong, Jianrong Li, Junya Fujimoto, Mehdi Chaib, Yuqiu Yang, Bo Wang, Alissa Poteete, Monique B Nilsson, Xiuning Le, Tina Cascone, David Jaffray, Nicholas Navin, Tao Wang, Lauren A Byers, Don L Gibbons, John Heymach, Ken Chen, Chao Cheng, Jianjun Zhang, Jia Wu

Faculty, Staff and Students Publications

Spatial domain detection methods often focus on high-variance structures, such as tumour-adjacent regions with sharp gene expression changes, while missing low-variance structures with subtle gene expression shifts, like those between adjacent normal and early adenoma regions. Here, to address this, we introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive feature representation framework. By comparing a target sample with a background sample, CoCo-ST detects both high-variance, broadly shared structures and low-variance, tissue-specific features. It offers technical advantages, including multisample integration, batch-effect correction and scalability across technologies from spot-level Visium data to single-cell Xenium Prime 5K and subcellular Visium HD …

Predictors Of Decannulation Success In Tracheostomy: A 10-Year Analysis Of The Global Tracheostomy Collaborative Database, Charissa J Zaga, Carly E Milliren, Brendan A Mcgrath, Christina J Yang, Bradley A Schiff, Stephen J Warrillow, Jennifer K Henningfeld, Prudence A Gregson, Joshua R Bedwell, Karen M Beaudet, Michael J Brenner, Vinciya Pandian

Faculty, Staff and Students Publications

Objective: Decannulation is a critical milestone in functional recovery after tracheostomy, but standardized guidelines are lacking. This study examined factors associated with tracheostomy decannulation success, comparing hospital utilization, adverse events, and survival outcomes between decannulated and non-decannulated patients.

Study design: Retrospective, observational study.

Setting: Data were collected from 25 hospitals participating in the Global Tracheostomy Collaborative (GTC) in the United States, Australia, and the United Kingdom.

Methods: Prospectively collected data from adult patients who underwent tracheostomy from 2013 to 2022 were analyzed. Outcomes included decannulation success, hospital utilization metrics (intensive care unit [ICU] admissions, mechanical ventilation use, tracheostomy duration, and …

Single-Nucleus Mrna-Sequencing Reveals Dynamics Of Lipogenic And Thermogenic Adipocyte Populations In Murine Brown Adipose Tissue In Response To Cold Exposure, Janina Behrens, Tongtong Wang, Christoph Kilian, Anna Worthmann, Mark A Herman, Joerg Heeren, Lorenz Adlung, Ludger Scheja

Faculty, Staff and Students Publications

Objective and methods: Brown adipose tissue (BAT) comprises a heterogeneous population of adipocytes and non-adipocyte cell types. To characterize these cellular subpopulations and their adaptation to cold, we performed single-nucleus mRNA-sequencing (snRNA-seq) on interscapular BAT from mice maintained at room temperature or exposed to acute (24h) or chronic (10 days) cold (6 °C). To investigate the role of the de novo lipogenesis (DNL)-regulating transcription factor carbohydrate response element-binding protein (ChREBP), we analyzed control and brown adipocyte-specific ChREBP knockout mice.

Results: We identified different cell populations, including seven brown adipocyte subtypes with distinct metabolic profiles. One of them highly expressed ChREBP …

Predicting Craving-Related Emotions Among Opioid Use Disorder Patients: Preliminary Results, Zachary King, Zoe Setiadi, Liana Hamdan, Hajar Ahmed, Bishal Lamichhane, Ashutosh Sabharwal, Ramiro Salas, Nidal Moukaddam, Akane Sano

Faculty, Staff and Students Publications

Individuals with Opioid Use Disorder (OUD) often struggle to maintain sobriety, with many experiencing relapse within the first year. While medication-assisted treatment (MAT) is among the most effective approaches, access to intensive care is often limited by financial barriers. Mobile health (mHealth) technologies offer a promising, cost-effective alternative by enabling continuous monitoring and timely intervention through tools such as ecological momentary assessments (EMAs), wearable sensors, and smartphone data. In this study, we explore the feasibility of using mHealth data to predict emotions that align with cravings in OUD patients undergoing MAT. Using data collected from EMAs, wearables, smartphone tracking, and …

Reprogrammed Glucose Metabolism In Vascular Smooth Muscle Cells And Its Implications For Vascular Diseases, Qian Ma, Yongfeng Cai, Qiuhua Yang, Wendy Zhang, Suowen Xu, Yuqing Huo

Faculty, Staff and Students Publications

Vascular smooth muscle cells (VSMCs) play a pivotal role in maintaining vascular homeostasis and are critical contributors to the pathogenesis of various vascular diseases, including atherosclerosis, calcification, aneurysms, and pulmonary hypertension. Emerging evidence highlights the significance of glucose metabolism in regulating VSMC phenotypic transitions during these pathologies. This review provides a comprehensive overview of the major glucose metabolic pathways in VSMCs, glycolysis, the pentose phosphate pathway (PPP), and the hexosamine biosynthetic pathway (HBP), and their roles in disease development. We summarize the molecular mechanisms linking glucose metabolic reprogramming to VSMC dysfunction, focusing on key regulatory enzymes and signaling pathways. Additionally, …

Inhibition Of Bmper Mitigates Pulmonary Hypertension By Modulating Lrp1-Yap Interaction In Smooth Muscle Cells, Hua Mao, Claire M Li, Bing Sun, Christopher S Ward, Alan R Waich-Cohen, Ivan O Rosas, Howard J Huang, Harry Karmouty-Quintana, Liang Xie, Lavannya M Pandit, Xinchun Pi

Faculty, Staff and Students Publications

Background: BMPER (bone morphogenetic protein-binding endothelial regulator) is a secreted protein that is highly expressed in endothelial cells. It regulates the BMP (bone morphogenetic protein) pathway during vascular development and adulthood. Mutations in the BMP pathway are recognized as risk factors for pulmonary arterial hypertension group 1 pulmonary hypertension (PH). However, the roles of BMPER in pulmonary arterial hypertension remain unknown.

Methods: We assessed BMPER expression in Group 1 pulmonary arterial hypertension patient samples and examined its role in vascular remodeling using in vivo and in vitro approaches.

Results: BMPER level was elevated in pulmonary arterial hypertension lungs and significantly …

Endothelial Adenosine Receptor 2a Loss Alleviates Diabetic Vascular Calcification By Blocking Creb1-Snai1-Driven Endmt, Yaqi Zhou, Dingwei Zhao, Qian Ma, Jiean Xu, Yongfeng Cai, Qiuhua Yang, Qingen Da, Kian Sheridan, Chunxiang Zhang, Clint L Miller, Rajeev Malhotra, Suowen Xu, Mei Hong, Yuqing Huo

Faculty, Staff and Students Publications

Vascular calcification (VC), a common complication associated with diabetes mellitus (DM), substantially increases the risk of cardiovascular diseases and is associated with elevated mortality in individuals with DM. Endothelial-to-mesenchymal transition (EndMT) imparts phenotypic plasticity to vascular endothelial cells (VECs), granting them the potential for osteogenic differentiation, which is a crucial mechanism in regulating VC. Notably, adenosine-ADORA2A-mediated endothelial dysfunction plays a pivotal regulatory role in cardiovascular diseases. However, the specific role of endothelial ADORA2A in diabetic VC remains to be elucidated. In this study, we found that ADORA2A was upregulated in the endothelium of diabetic mice and cultured human aortic endothelial …

Pediatric Heart-Kidney Transplantation, Swati Choudhry, Kriti Puri, Vikas R Dharnidharka

Faculty, Staff and Students Publications

Heart transplantation is regarded as the definitive treatment for advanced pediatric heart failure. However, concomitant kidney dysfunction often complicates candidate selection for isolated heart transplantation. Prolonged venous congestion, nephrotoxic exposures, and recurrent episodes of acute kidney injury can result in varying degrees of renal impairment. Differentiating between reversible kidney injury secondary to cardiorenal syndrome and irreversible intrinsic renal disease remains a major challenge. Pediatric heart-kidney transplantation has shown survival benefits for patients with end-stage heart failure requiring chronic dialysis, yet its role in patients with less severe renal dysfunction is less clearly defined. This review summarizes the current evidence on …

Ambulatory Acute Kidney Injury In Patients With Cirrhosis Is Common And Burdensome, Kavish R Patidar, Ruben Hernaez, Yan Liu, George Cholankeril, Jennifer R Kramer, Thom Taylor, Prasun Jalal, Tzu-Hao Lee, Avegail G Flores, Giuseppe Cullaro, Andrew S Allegretti, Pere Gines, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: Little is known about ambulatory acute kidney injury (A-AKI), which develops in an outpatient setting.

Methods: We conducted a retrospective cohort study of patients diagnosed with cirrhosis between January 1, 2018, and December 31, 2019 from 130 hospitals in the Veterans Affairs healthcare system. Patients were classified as having incident A-AKI if they met the International Club of Ascites AKI criteria in an outpatient setting. We used multivariable regression models to identify factors associated with A-AKI development within 1 year of cirrhosis diagnosis. We also conducted a structured implicit review of patients' medical charts to determine the …

Missing The Target: A Scoping Review Of The Use Of Percent Weight Loss For Obesity Management, Diana Sherifali, Megan Racey, Donna Fitzpatrick-Lewis, Michelle Greenway, Sanjeev Sockalingam, Jun Wada, Soo Huat Teoh, Ian Patton, David Macklin, Elizabeth F C Van Rossum, Luca Busetto, Deborah Bade Horn, J D Patricia Nece, Morgan Emile Gabriel Salmon Leguede, Nicole Pearce, Carel Le Roux, Jamy Ard, Angela S Alberga, Lee Kaplan, Arya M Sharma, Sean Wharton

Faculty, Staff and Student Publications

Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.

Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted …

Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis In Ectopic Cushing Syndrome, Raghavendra Pandit, Chethan Yamichannaiah, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Tushar Bandgar

Faculty, Staff and Student Publications

A woman in her fourth decade of life with metastatic ectopic Cushing syndrome due to a thymic neuroendocrine tumor developed an acute adrenocorticotropin (ACTH)-mediated hypercortisolemic crisis 5 days after initiating lutetium-177-labeled DOTA-[Tyr3]-octreotate (177Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). She presented with hypertension, rapid weight gain (8 kg in a week), psychosis, and biochemical evidence of severe hypercortisolism: serum cortisol: 141 µg/dL (SI: 3889.7 nmol/L) (reference range, 5-25 µg/dL [SI: 137.9-689.7 nmol/L]), plasma ACTH greater than 2000 pg/mL (SI >440.4 pmol/L) (reference range, 10-60 pg/mL [SI: 2.2-13.3 pmol/L]), potassium: 3.4 mEq/L (reference range, 3.5-5.0 mEq/L). Low-dose intravenous etomidate (0.02 mg/kg/h) was …

Two Decades Of Diagnostic Safety Research: Advances, Challenges, And Next Steps, Sundas Khan, Andrea Bradford, Christina L Cifra, Hardeep Singh

Faculty, Staff and Students Publications

Since the National Academies of Sciences, Engineering, and Medicine (NASEM) report Improving Diagnosis in Health Care, various research efforts have accelerated progress to understand and improve diagnostic safety. In this opinion piece, we summarize two decades of progress in methods for identifying and learning from diagnostic errors and provide recommendations for future research. Multiple methods have been used to quantify diagnostic errors in various clinical settings, thereby facilitating a deeper understanding of the nature and magnitude of the problem and enabling studies of contributing factors. However, the use of standardized definitions of a diagnostic error and/or diagnostic safety event, …

Foreword: Addressing Diagnostic Error: The First 10 Years, Mark L Graber, Edward P Hoffer, Hardeep Singh

Faculty, Staff and Students Publications

No abstract provided.

Safety And Efficacy Of Liver-Directed Radiotherapy After Chemoimmunotherapy For Advanced Cholangiocarcinoma: An Early Report From A Large Tertiary Cancer Center, Abdulmoiz Asif, Abdulmoid Asif, Michael K Rooney, Enoch Chang, Felicity Namayanja, Kimana Quentin, Sunyoung Lee, Ian Hu, Vincent Bernard, Prajnan Das, Emma B Holiday, Sonal Noticewala, Grace L Smith, Albert C Koong, Ethan B Ludmir, Milind Javle, Lianchun Xiao, Eugene J Koay

Faculty, Staff and Student Publications

BACKGROUND: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy.

METHODS: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range …

Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective Of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience, Gabriela Llaurador, Matthew Willis, Michele S Redell, M Monica Gramatges, Andrea N Marcogliese, Swati Naik, Robert Krance, Erin Doherty, Alexandra M Stevens

Faculty, Staff and Students Publications

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1).

Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort.

Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children's Hospital from 2000 to 2022 was conducted.

Results: Twenty-nine …

Resolving Slc6a1 Variable Expressivity With Deep Clinical Phenotyping And Drosophila Models, Kristy L Jay, Nikhita Gogate, Paige I Hall, Kimberly M Ezell, Jonathan C Andrews, Sharayu V Jangam, Hongling Pan, Kelvin Pham, Ryan German, Vanessa Gomez, Emily Jellinek-Russo, Eric A Storch, Brain Gene Registry Consortium, Undiagnosed Diseases Network, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Herman A Dierick, Joy D Cogan, John A Phillips, Rizwan Hamid, Thomas Cassini, Lynette Rives, Sumit Pruthi, Hua-Chang Chen, Jennifer E Posey, Michael F Wangler

Faculty, Staff and Students Publications

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficiency has been confirmed as the predominant pathway of SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD); however, the molecular mechanism underlying the variable clinical presentation remains unclear. Here, through work of the Undiagnosed Diseases Network, we identify an individual with an inherited p.A334S variant of uncertain significance. To resolve this variant and better understand the variable expressivity associated with SLC6A1, we assess the phenotypes of the proband in comparison with a cohort of 13 individuals …

Urinary Vitamin D Binding Protein And Kidney Injury Molecule-1 Are Potent Predictors Of Acute Kidney Injury After Left Ventricular Assist Device Implantation, Shiyi Li, Iván Murrieta-Álvarez, Katherine V Nordick, Zachary Gray, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

Background/Objectives: Acute kidney injury (AKI) is a frequent and serious complication following left ventricular assist device (LVAD) implantation. This study aimed to predict AKI within 90 days post-LVAD by evaluating urinary levels of vitamin D binding protein (VDBP) and kidney injury molecule-1 (KIM-1).

Methods: We prospectively enrolled 29 advanced heart failure patients undergoing LVAD implantation and categorized them into four groups based on pre-LVAD kidney function and hemodynamic stability. Early-morning urine samples were collected 24 h before and 1 week after surgery. Urinary VDBP and KIM-1 levels, normalized to creatinine, were measured.

Results: Thirteen patients developed AKI …

Distinct Molecular Responses Of Human Intestinal Organoids To Proton And Photon Radiation, Victoria Poplaski, Tajhal D Patel, Hoa Nguyen-Phuc, Amal Kambal, Lawrence Bronk, Mary K Estes, Cristian Coarfa, Sarah E Blutt

Faculty, Staff and Students Publications

Radiation exposure impairs rapidly renewing tissues like the intestinal epithelium, yet translational insights from murine models have been limited by species-specific responses. Here, we use human intestinal organoids (HIOs) derived from jejunal epithelium to evaluate human epithelial responses to low dose proton and photon (gamma) radiation. Gamma irradiation induces a unique developmental and metabolic shift in crypt-like organoids, including enrichment of amino acid metabolism pathways and activation of fetal-associated transcription factors and morphology. Integrated multi-omic profiling reveals serotonin biosynthesis as a central regenerative node. Human intestinal organoids can complement animal models and are emerging as a powerful tool in modeling …

Erratum To <[Transplant Cell Ther 2023 Jul;29(7):438e1-438e16 Epub 2023 Mar 9]>, Melissa R Hines, Tristan E Knight, Kevin O Mcnerney, Mark B Leick, Tania Jain, Sairah Ahmed, Matthew J Frigault, Joshua A Hill, Michael D Jain, William T Johnson, Yi Lin, Kris M Mahadeo, Gabriela M Maron, Rebecca A Marsh, Sattva S Neelapu, Sarah Nikiforow, Amanda K Ombrello, Nirav N Shah, Aimee C Talleur, David Turicek, Anant Vatsayan, Sandy W Wong, Marcela V Maus, Krishna V Komanduri, Nancy Berliner, Jan-Inge Henter, Miguel-Angel Perales, Noelle V Frey, David T Teachey, Matthew J Frank, Nirali N Shah

Faculty, Staff and Student Publications

No abstract provided.

Final Analysis Of The Resonate-2 Study: Up To 10 Years Of Follow-Up Of First-Line Ibrutinib Treatment For Cll/Sll, Jan A Burger, Paul M Barr, Tadeusz Robak, Carolyn Owen, Alessandra Tedeschi, Anita Sarma, Piers E M Patten, Sebastian Grosicki, Helen Mccarthy, Fritz Offner, Edith Szafer-Glusman, Cathy Zhou, Anita Szoke, Lynne Neumayr, James P Dean, Paolo Ghia, Thomas J Kipps

Faculty, Staff and Student Publications

With up to 10 years of follow-up, we report results from the final analysis of RESONATE- 2, a phase 3 study of first-line ibrutinib vs chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/d; n = 136) or chlorambucil (0.5-0.8 mg/kg; ≤12 cycles; n = 133). With a median follow-up of 9.6 years in the ibrutinib arm, the median progression-free survival (PFS) was 8.9 years (95% confidence interval [CI], 7.0 to not estimable [NE]) vs 1.3 years (95% …

A Single-Nucleus Transcriptomic Atlas Of The Adult Aedes Aegypti Mosquito, Olivia V Goldman, Alexandra E Defoe, Yanyan Qi, Yaoyu Jiao, Shih-Che Weng, Brittney Wick, Leah Houri-Zeevi, Priyanka Lakhiani, Takeshi Morita, Jacopo Razzauti, Adriana Rosas-Villegas, Yael N Tsitohay, Madison M Walker, Ben R Hopkins, Aedes Aegypti Mosquito Cell Atlas Consortium, Maximilian Haeussler, Omar S Akbari, Laura B Duvall, Helen White-Cooper, Trevor R Sorrells, Roshan Sharma, Hongjie Li, Leslie B Vosshall, Nadav Shai

Faculty, Staff and Students Publications

The female Aedes aegypti mosquito's remarkable ability to hunt humans and transmit pathogens relies on her unique biology. Here, we present the Aedes aegypti Mosquito Cell Atlas, a comprehensive single-nucleus RNA sequencing dataset of more than 367,000 nuclei from 19 dissected tissues of adult female and male Aedes aegypti, providing cellular-level resolution of mosquito biology. We identify novel cell types and expand our understanding of sensory neuron organization of chemoreceptors across all sensory tissues. Our analysis uncovers male-specific cells and sexually dimorphic gene expression in the antenna and brain. In female mosquitoes, we find that glial cells, rather than neurons, …

Cohesin Haploinsufficiency Is Tolerated In Cbfb::Myh11-Driven Murine Acute Myeloid Leukemia, Shannon E Conneely, Alexis Quezada, Kristen J Kurtz, Nenggang Zhang, Josephine De La Fuente, Nesa Mercer, Jason H Rogers, Rogelio Aguilar, Geraldo Medrano, Margaret A Goodell, Paul P Liu, Debananda Pati, Rachel E Rau

Faculty, Staff and Students Publications

Cohesin gene mutations occur in many malignancies, including acute myeloid leukemia (AML). Loss-of-function mutations in the four major cohesin complex genes (RAD21, SMC3, SMC1a, and STAG2) occur across most major genetic subtypes of AML but are notably absent in AML harboring CBFB::MYH11, suggesting that cohesin mutations yield distinct biological outcomes dependent on the genetic AML driver. We hypothesized that CBFB::MYH11-expressing leukemias would be dependent on intact cohesin genes given their near-mutual exclusivity. To investigate this, we combined either germline or inducible heterozygous deletions in cohesin genes Smc3 or Rad21, respectively, with an inducible murine model of Cbfb::MYH11 AML. This approach …

Longitudinal Characterization Of Males With X-Linked Creatine Transporter Deficiency: Final Results Of A Multiyear Observational Study, Judith S Miller, Cristan Farmer, Susan Blair, Simona Bianconi, Natacha Akshoomoff, Irina Anselm, Bruce A Barshop, Lindsey Becker, Amanda E Bennett, Leandra N Berry, Elizabeth M Berry-Kravis, Aleksandra Bruchey, Anna W Byars, Tricia Cimms, Kim M Cecil, Maxine Covello, Laura S Cubit, Tanvi Das, Robert J Davis, Madison Drye, Can Ficicioglu, John B Fulton, Robin P Goin-Kochel, Whitney Guthrie, Barbara E Hallinan, Fady Hannah-Shmouni, Kathryn E Gustafson, Dwight D Koeberl, Nicola Longo, Eva Mamak, Saadet Mercimek-Andrews, Claire Michalak, Forbes D Porter, Samar Rahhal, Linda Rees, Gail A Spiridigliozzi, Caitlin Stone, Nancy R Sullivan, V Reid Sutton, Rebecca P Thomas, Manisha Udhnani, Susan Waisbren, Michelle Xu, Lin Zhang, Melanie Brandabur, Audrey Thurm

Faculty, Staff and Students Publications

Background: The purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD).

Methods: Males with CTD aged 6 months to 65 years were evaluated at 6-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, and challenging behaviors and the onset and progression of medical comorbidities.

Results: Fifty participants (median age, 7.6 years) were enrolled. The predominant CTD phenotype consisted of significant intellectual disabilities and limited skill development over time. Most participants had a history of febrile or nonfebrile seizures, …

Insights Into Spheroid Formation: Interaction Of Ovarian Cancer Cells With Macrophage Populations In The Tumor Microenvironment, Simone Pisano, Yajaira Sofia Jimenez, Paul Rees, Jing Xiao, Deyarina Gonzalez, Robert Steven Conlan, Bruna Corradetti

Faculty, Staff and Students Publications

Background: Treating advanced ovarian cancer (OC) is challenging due to the immunosuppressive tumor microenvironment. This study investigates tumor-immune cell interactions using organotypic spheroid models that simulate the in vivo microenvironment.

Methods: A dual-model spheroid system was established combining serous adenocarcinoma SKOV-3 cells with monocytes, pro-inflammatory (MΦ1) or anti-inflammatory (MΦ2) macrophages, or their derived exosomes (EXOs). In Model A, immune cells or EXOs were co-seeded with tumor cells to replicate early heterotypic aggregation. In Model B, immune cells or EXOs were introduced 24 h post-spheroid formation to simulate immune infiltration into established spheroids. Spheroid morphology was quantified by diameter and circularity, …

Nasal Microbionts Differentially Colonize And Elicit Cytokines In Human Nasal Epithelial Organoids, Andrea I Boyd, Leah A Kafer, Isabel F Escapa, Amal Kambal, Hira Tariq, Susan G Hilsenbeck, Hoa Nguyen-Phuc, Anubama Rajan, Joshua M Lensmire, Kathryn A Patras, Pedro A Piedra, Sarah E Blutt, Katherine P Lemon

Faculty, Staff and Students Publications

Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by Dolosigranulum species is associated with health. Human nasal epithelial organoids (HNOs) differentiated at air-liquid interface (ALI) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. Due to their natural stem-like properties, HNO lines are a long-term experimental resource that offers genetic diversity based on the different donors. To develop HNOs as a new model system for bacterial nasal colonization, we reproducibly monocolonized HNOs differentiated at ALI with S. aureus, S. pneumoniae, or Dolosigranulum …

Prevalence And Clinical Impact Of Pseudohypercalcemia In Paraproteinemia: A Case And Cohort Study, Usman Sunusi, Li Chen, Nianyi Li, Jason K Y Lee, Irmeen Siddiqui, Erin Goodhue, Rongrong Huang, Jieli Li

Faculty, Staff and Students Publications

Background: Hypercalcemia is a common and serious complication of malignancy, often contributing to morbidity and mortality. In patients with paraproteinemia, elevated total calcium with normal ionized calcium, termed pseudohypercalcemia, can complicate diagnosis and lead to inappropriate treatment. While this phenomenon has been described in case reports, its prevalence and clinical impact in routine practice remain poorly defined.

Methods: We report a case of pseudohypercalcemia in a patient with IgG κ multiple myeloma and conducted a retrospective review of de-identified data to assess the prevalence and biochemical associations of pseudohypercalcemia in paraproteinemia. Available data included serum protein electrophoresis (SPEP), …

Translational Framework Linking Perfluoroheptanoic Acid (Pfhpa) Exposure To Metabolic Dysfunction Associated Steatotic Liver Disease In Adolescents, Brittney O Baumert, Ana C Maretti-Mira, Douglas I Walker, Zhenjiang Li, Nikos Stratakis, Hongxu Wang, Yinqi Zhao, Fabian Christoph Fischer, Qiran Jia, Damaskini Valvi, Scott M Bartell, Jiawen Carmen Chen, Thomas Inge, Justin R Ryder, Todd Jenkins, Stephanie Sisley, Stavra Xanthakos, David E Kleiner, Rohit Kohli, Sarah Rock, Sandrah P Eckel, Michele A La Merrill, Max M Aung, Matthew P Salomon, Rob Mcconnell, Jesse Goodrich, David V Conti, Lucy Golden-Mason, Lida Chatzi

Faculty, Staff and Students Publications

Background: The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), particularly among pediatric populations, requires identification of modifiable risk factors to control disease progression. Per- and polyfluoroalkyl substances (PFAS) have emerged as potential contributors to liver damage; however, their role in MASLD remains underexplored. This study aimed to develop a translational framework integrating human and in vitro data to elucidate the effect of PFAS on MASLD development.

Methods: We measured PFAS plasma levels in the Teen-LABS cohort (n = 136), comprising adolescents with obesity (mean age = 16.8 years) undergoing bariatric surgery. Plasma samples were also analyzed using proteomic …

Fastk Post-Transcriptional Regulators – A ‘Fast-Track’ In Mitochondrial Gene Expression, Justin Van Riper, Bridget J Corsaro, Monica C Pillon

Faculty, Staff and Students Publications

Fas-activated serine/threonine kinase (FASTK) proteins comprise one of the largest families of mitochondrial post-transcriptional regulators. Members are classified based on their conserved C-terminus, which shows homology with the PD-(D/E)XK superfamily of endoribonucleases. However, it is still uncertain which of these FASTK members are catalytic. The six human FASTK homologs rely on their RNA-binding activity to regulate distinct stages of mitochondrial gene expression, including early processing of nascent RNA, 3'-end messenger RNA (mRNA) maturation, ribosomal RNA (rRNA) modification, mRNA stability, and translation. Genetic and genomic studies have highlighted the crucial role of FASTK proteins in balancing the mitochondrial transcriptome and controlling …