Medical Specialties Commons^™

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Clinical Phenotypes Of Motor Neurone Disease In A Kenyan Hospital-Based Population, Effie Nailah Kamadi, Jasmit Shah, Juzar Hooker, Thomas Jenkins, Dilraj Sokhi

Internal Medicine, East Africa

Background: Motor neurone disease (MND) presentation is globally heterogenous and data on the clinical phenotype in Sub-Saharan Africa (SSA) is scarce. We sought to address this by describing the profile of MND patients in a Kenyan hospital-based population.

Methods: The medical charts of all adult MND patients assessed in the facility between January 2010 and December 2023 were retrospectively reviewed. The biographical data and clinical features of these patients were captured from their electronic and manual health records and statistical analysis performed.

Results: In total, 160 patients had their data analyzed. The male to female ratio was 1.76:1. The median …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Dual-Task Interaction Between Vestibular Function And Cognitive Processing Using The P300 Event-Related Potential, Laurel Elise Money-Nolan

Graduate Theses and Dissertations (2019 - present)

Previous research has established links between vestibular function and cognitive processing, aging and cognitive function, and aging and vestibular function. Theories of cognitive resource allocation discuss how cognitive resources, such as attention, are devoted towards and divided between tasks when multitasking. This dual-task study, utilizing a balance task and a listening/cognitive task, across the young- and middle-aged adult age range, aimed to evaluate potential relationships between vestibular function, cognition, and age, and to examine how cognitive resources might be allocated under dual-task conditions.

The dual-task protocol in this study utilized an oddball paradigm with tonal stimuli to measure the P300 …

Surgical Removal Of Implanted Microchips To Correct Mri Susceptibility Artifacts In Mice, Elizabeth Hipskind, Nicole Hernandez, Sydney Fox, Tina Manirambona, Rita Schack, Brian Gibson, Robia G Pautler

Center on Aging Staff Publications

Purpose: Implanted microchips are becoming increasingly common in research for animal identification and have been adopted by commercial vendors for some mouse strains. However, they often contain metal components, which generate magnetic susceptibility artifacts on MR images. Despite this, some microchips are marketed as MR-compatible, even though they are likely to affect image quality.

Methods: We assessed the impact of a radiofrequency identification microchip on MR images of the mouse brain and present a method for precise surgical removal. A handheld magnet was used to locate and stabilize the microchips during removal. Mice were imaged before and after microchip removal. …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy Grossman, Zhen Zhao

Student Papers, Posters & Projects

BACKGROUND: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

PATIENTS/MATERIALS AND METHODS: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Cumulative Triglyceride-Glucose Index And Hypertension Risk: A Longitudinal Cohort Study, Zhaogui Wu, Dan Wu, Sichi Xu, Yan Borné, Yulong Lan, Shuohua Chen

Research outputs 2022 to 2026

Background: Prior research has established a positive association between the single-measured triglyceride-glucose (TyG) index and hypertension. Nevertheless, longitudinal studies addressing the enduring impact of TyG index on incident hypertension are lacking. This study sought to explore the association between cumulative TyG index (cum-TyG) and incident hypertension, especially obesity-related hypertension (ORHT). Methods: A total of 21,017 individuals [mean (SD) age: 48.5 ± 11.7 years, male (%): 14,544 (69.2)] without hypertension were recruited from the Kailuan Study. The cum-TyG was determined by multiplying the mean TyG index by the time intervals between successive visits. Multivariable Cox regression models were used to investigate …

Impact Of Exercise In Patients With Pancreatic Cancer Across Different Treatment Phases: A Systematic Review, Linda Toniolo, Anita Borsati, Cristina Crespo-Garcia, Diana Giannarelli, Christian Ciurnelli, Gloria Adamoli, Lorenzo Belluomini, Ilaria Trestini, Daniela Tregnago, Federico Schena, Robert U. Newton, Salvatore Paiella, Roberto Salvia, Michele Milella, Sara Pilotto, Alice Avancini

Research outputs 2022 to 2026

Background: With a dismal prognosis of 8–10 % 5-year survival since diagnosis, pancreatic cancer remains one of the most aggressive oncological diseases. This work aimed to evaluate the effects of exercise medicine on safety and feasibility, physical fitness, body composition, patient-reported outcomes, and clinical outcomes across different treatment phases in patients with pancreatic cancer. Method: PubMed, Cochrane, and Scopus databases were systematically screened to identify single-arm studies and randomized/non-randomized controlled trials investigating a physical exercise intervention in patients with pancreatic cancer. The RoB 2 and ROBINS-I tools were used to evaluate study quality for randomized and non-randomized studies, respectively. Qualitative …

Hypercalcemia Of Down Syndrome., Seth Lmb, Melissa Litao, Nasreen Talib, Jacob M. Redel

Manuscripts, Articles, Book Chapters and Other Papers

We present a case of hypercalcemia in a 12-month-old female with Down syndrome. The patient presented with significant weight loss (810 g since her 6-month visit) and severe growth failure (weight 5.8 kg, -4.5 SDs). Laboratory evaluation revealed severe hypercalcemia with appropriately suppressed PTH and 1,25-hydroxyvitamin D levels. Renal ultrasound confirmed medullary nephrocalcinosis. After excluding common etiologies, the patient was diagnosed with hypercalcemia of Down syndrome, also termed Abnormal Calcium, Calcinosis, Creatinine in Down syndrome. Treatment with intravenous fluids, calcitonin, and transition to a low-calcium formula (Calcilo XD) normalized serum calcium levels. The patient maintained normal calcium levels on restricted …

Elevated Serum Bile Acids Predict Poor Liver Outcomes In Children With Alagille Syndrome: Results From The Gala Study Group., Carla Fiorella Murillo Perez, Shannon M. Vandriel, Emmanuel M. Gonzales, Jian-She Wang, Li-Ting Li, Huiyu She, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Emmanuel Jacquemin, Jérôme Bouligand, Lorenzo D'Antiga, Emanuele Nicastro, Björn Fischler, Henrik Arnell, Susan M. Siew, Michael Stormon, Kathleen M. Loomes, David A. Piccoli, Elizabeth B. Rand, James E. Squires, Saul J. Karpen, Rene Romero, Mureo Kasahara, Zerrin Önal, Étienne Sokal, Tanguy Demaret, Sabina Wiecek, Florence Lacaille, Dominique Debray, Winita Hardikar, Sahana Shankar, Pamela L. Valentino, Shikha S. Sundaram, Noelle H. Ebel, Jeffrey A. Feinstein, Orith Waisbourd-Zinman, Henry C. Lin, Nathalie Rock, Henkjan J. Verkade, M Kyle Jensen, Catalina Jaramillo, Kyung Mo Kim, Seak Hee Oh, Jernej Brecemiclj, Seema Alam, Giuseppe Indolfi, Niviann Blondet, Rima Fawaz, Silvia Nastasio, Pier Luigi Calvo, Gabriella Nebbia, Cigdem Arikan, Catherine Larson-Nath, Andréanne N. Zizzo, Thomas Damgaard Sandahl, Christos Tzivinikos, Nehal M. El-Koofy, Mohamed A. Elmonem, Amal A. Aqul, Wikrom Karnsakul, Pinar Bulut, Nanda Kerkar, Victorien M. Wolters, Amin J. Roberts, Helen M. Evans, Maria Camila Sanchez, Maria Lorena Cavalieri, Deirdre A. Kelly, Jane Hartley, Way Seah Lee, Christina Hajinicolaou, Chatmanee Lertudomphonwanit, Ryan T. Fischer, Jesus Quintero Bernabeu, Ruben E. Quiros-Tejeira, Cristina Targa Ferreira, Elisa Carvalho, John Eshun, Aglaia Zellos, Antal Dezsőfi, Raquel Borges Pinto, Kathleen Schwarz, Maria Rogalidou, Jennifer Garcia, María Legarda Tamara, Marisa Beretta, Quais Mujawar, Ermelinda Santos-Silva, Cristina Molera Busoms, Eberhard Lurz, Cristina Gonçalves, Carolina Jimenez-Rivera, Jesus M. Banales, Richard J. Thompson, Bettina E. Hansen, Binita M. Kamath, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND AIM: Alagille syndrome (ALGS) is a rare disorder characterised by cholestasis and extrahepatic manifestations. Given the current era of ileal bile acid transporter (IBAT) inhibitor therapies that reduce serum bile acid (SBA) levels, we evaluated whether SBA predicts liver disease outcomes in ALGS.

METHODS: Patients were ascertained from the Global ALagille Alliance (GALA) cohort. A prognostic threshold of SBA 102 μmol/L was assessed as a time-dependent covariate in Cox regression analyses for native liver survival (NLS) and event-free survival (EFS), while adjusting for total bilirubin (TB) levels.

RESULTS: 570 GALA patients were included (348 [61%] male). There was …

Acceptability Of Corticosteroid Use In The Treatment Of Infant Bronchiolitis: Utilizing The Theoretical Framework Of Acceptability To Design Research Instruments, Caroline R. Smetanka

Capstone Experience: Master of Public Health

Bronchiolitis is the leading cause of hospitalization among infants under six months, yet treatment remains largely supportive due to clinical guidelines that discourage pharmacologic intervention. Recent research suggests that bronchiolitis is not a uniform condition, and a subgroup of infants (those classified within “Profile A”) may benefit from targeted corticosteroid therapy. However, these treatments remain outside current clinical guidelines, and their successful adoption depends on stakeholder acceptability. This Capstone project developed and refined four data collection instruments- two questionnaires and two interview guides- designed to assess how healthcare providers and caregivers perceive the acceptability of corticosteroid treatment for Profile A …

The Association Between Gestational Body Mass Index Change, Cesarean Section, And Other Pregnancy Outcomes: Research Protocol: Retrospective Cohort Analysis, Kirsten I. Black, Owen Streeter, Arianne Sweeting, Pejman Adily, Mark Lauer, Adrienne Gordon, Vincenzo Berghella, Belinda R. Bruce, Lauren Ferris, Bradley De Vries

Department of Obstetrics and Gynecology Faculty Papers

Increasingly the value of gestational weight gain (GWG) as a useful measure to predict obstetric outcomes including cesarean section is being questioned. We will undertake a retrospective cohort study of recorded births in 2023 from 24 to 42 weeks' gestation for women aged from 16 to 49 years in the United States. Using multivariable Robust Poisson Regression, maternal body mass index (BMI) and BMI gain will be modelled on the primary outcome of cesarean delivery. The primary analysis will be restricted to nulliparous women if there is interaction between parity and BMI or BMI gain. A sample of 716,392 births …

Loss Of The Lysosomal Protein Cln3 Triggers C-Abl-Dependent Yap1 Pro-Apoptotic Signaling, Neuza Domingues, Alessia Calcagni', Sofia Freire, Joana Pires, Ricardo Casqueiro, Ivan L Salazar, Niculin Joachim Herz, Tuong Huynh, Katarzyna Wieciorek, Tiago Fleming Outeiro, Henrique Girão, Ira Milosevic, Andrea Ballabio, Nuno Raimundo

Duncan NRI Faculty and Staff Publications

Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protein. Currently, no therapies targeting disease progression are available, largely because its molecular mechanisms remain poorly understood. To understand how CLN3 loss affects cellular signaling, we generated human CLN3 knock-out cells (CLN3-KO) and performed RNA-seq analysis. Our multi-dimensional analysis reveals the transcriptional regulator YAP1 as a key factor in remodeling the transcriptome in CLN3-KO cells. YAP1-mediated pro-apoptotic signaling is also increased as a consequence of CLN3 functional loss in retinal pigment …

From Bladder To Brain: How You Know When It’S Time To Go, Anne M J Verstegen, Kara L Marshall

Duncan NRI Faculty and Staff Publications

The decision to urinate relies on assessing bladder fullness and context to determine an appropriate time and place to go. Any disruption in this interoceptive process results in frequent and sometimes debilitating consequences in daily life. Recent work has uncovered key pathways and brain regions that contribute to the sense of bladder stretch and the control of urinary reflexes, but many open questions remain. Here, we review the known mechanisms that convey sensory information from the bladder to the brain and back down again, and we highlight the knowledge gaps and opportunities for better understanding this system, which will be …

Transoral Robotic-Assisted Removal Of A Submucosal Pyriform Sinus Foreign Body, Elisabeth Wenneker, Rebecca Doctor, Ari Schuman, Adam Szymanowski, Ray Wang

Faculty, Staff and Students Publications

Background: Submucosal foreign bodies of the medial pyriform sinus represent a challenge given limited visualization and difficult retraction with endoscopic approaches, and risk of injury to the recurrent laryngeal nerve with open approaches. Transoral robotic surgery (TORS) offers improved visualization and multiple working arms to facilitate retraction. We present a novel case utilizing the Da Vinci SP system for removal of an embedded fishbone of the medial pyriform sinus.

Results: An 84-year-old woman presented with five days of odynophagia and globus sensation after swallowing a fish bone. Non-contrast computed tomography scan revealed a 3.0 cm submucosal object within the post-cricoid …

Screening For Diabetes After Solid Organ Transplantation: A 10-Year Retrospective Study, Ridwan B Ibrahim, Sneha Kumar, Sahil Malik, Joseph A Spinner, Daniel H Leung, Sridevi Devaraj

Faculty, Staff and Students Publications

Post-transplantation diabetes mellitus (PTDM) is a common and important complication after solid organ transplantation, affecting long-term outcomes. Graft rejection, decreased patient survival, infections and increased cardiovascular risk are associated with PTDM and may arise from both transplant-related and traditional risk factors. Early screening for PTDM is crucial for early detection and management. Despite clinical guidelines recommending regular screening for PTDM, screening rates remain suboptimal. This retrospective study analyzes PTDM screening rates between January 2014-January 2024 among pediatric kidney, liver, heart and lung transplant recipients at a large quaternary academic pediatric transplant center. PTDM screening rates vary by organ type, with …

Corrigendum To “Clinical Characteristics And Longitudinal Associations With Obsessive-Compulsive Disorder In Youth Exposed To Trauma” [J Mood Anxiety Disord 10c (2025) 100117], Caitlin M Pinciotti, Paul J Rathouz, Andrew G Guzick, Jeffrey D Shahidullah, Emily J Bivins, David B Riddle, Ogechi Cynthia Onyeka, Eric A Storch, Wayne K Goodman, Kelli Franco, Justin F Rousseau, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff

Faculty, Staff and Students Publications

This corrects the article "Clinical characteristics and longitudinal associations with obsessive-compulsive disorder in youth exposed to trauma" in volume 10, 100117.

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

Mecom Fusion Partner And Bone Marrow Blast Percentage Influence Outcomes Of Patients With Mecom Rearranged Acute Myeloid Leukaemia, Wei-Ying Jen, Guilin Tang, Eitan Kugler, Jennifer Croden, Koji Sasaki, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Gautam Borthakur, Gokce A Toruner, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Ian M Bouligny, Sherry Pierce, Uday Popat, Naveen Pemmaraju, Elias Jabbour, Guillermo Garcia-Manero, Kapil Bhalla, Farhad Ravandi, Naval G Daver, Courtney D Dinardo, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

MECOM rearrangements (MECOM-r) are acute myeloid leukaemia (AML)-defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM-r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM-r and classified blast percentage into < 20% or ≥20% and MECOM-r partner into classic (GATA2::MECOM) or variant (others). Thirty-one per cent had < 20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM-r. Treatment was with intensive chemotherapy (IC) in 41% and low-intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval [CI], 12-not estimable [NE]) for < 20% blasts, compared with 9 months (95% CI, 6-10) for ≥20% blasts (p <  0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p <  0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1-3.7, p = 0.03). In < 20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 [95% CI, 0.1-0.8], p <  0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.

The Pneumonia Challenge: Time To End The Global Neglect, Catia Cillóniz, Markus Fally, Scott Evans, Guinevere Dy-Agra, Pneumo-Strategy Group

Faculty, Staff and Student Publications

No abstract provided.

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Author Correction: Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

No abstract provided.

Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. …