Digital Commons Network^™

Predictors Of Transition From Child And Adolescent Bipolar Not Otherwise Specified To Bipolar I Disorder, A Longitudinal 3.9-Year Study., María Ribeiro-Fernández, Azucena Díez-Suárez, Kiki D Chang, Cesar A Soutullo

Faculty, Staff and Student Publications

Background: Children and adolescents with subthreshold manic symptoms not meeting full DSM criteria for bipolar I or II disorder (BP-I or BP-II) are classified as unspecified bipolar disorder (formerly bipolar not otherwise specified: BP-NOS). Factors associated with transition from BP-II or NOS to BP-I may predict the progression of the disorder. Our objective is to analyze factors associated with transition to BP-I in a Spanish sample of youth with BP-NOS or BP-II.

Methods: We included all youth diagnosed with BP before 18 years of age presenting to our clinic (October 1999-December 2014). We assessed clinical factors that may predict transition …

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Ningbo Zheng, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

Metadegron: Multimodal Feature-Integrated Protein Language Model For Predicting E3 Ligase Targeted Degrons, Mengqiu Zheng, Shaofeng Lin, Kunqi Chen, Ruifeng Hu, Liming Wang, Haodong Xu

Faculty, Staff and Student Publications

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive …

Thrombectomy For Stroke With Large Infarct On Noncontrast Ct: The Tesla Randomized Clinical Trial, Ansaar T Rai, Ramesh Grandhi, Hugo Cuellar, Maxim Mokin, Jeffrey M Katz, Amer Alshekhlee, Muhammad A Taqi, Sameer A Ansari, Adnan H Siddiqui, Nobl Barazangi, Joey D English, Alberto Maud, Jawad Kirmani, Rishi Gupta, Dileep R Yavagal, Jason Tarpley, Dhruvil J Pandya, Marshall C Cress, Sushrut Dharmadhikari, Kaiz S Asif, Tareq Kass-Hout, Ajit S Puri, Nazli Janjua, Aniel Q Majjhoo, Aamir Badruddin, Randall C Edgell, Rakesh Khatri, Larry Morgan, Anmar Razak, Alicia Zha, Priyank Khandelwal, Nils Mueller-Kronast, Dennis J Rivet, Thomas Wolfe, Brian Snelling, Ali Sultan-Qurraie, Shao-Pow Lin, Rajkamal Khangura, Alejandro M Spiotta, Parita Bhuva, Sergio Salazar-Marioni, Eugene Lin, Abdul R Tarabishy, Edgar A Samaniego, Murali K Kolikonda, Mouhammad A Jumaa, Vivek K Reddy, Pankaj Sharma, Olvert A Berkhemer, Pieter-Jan Van Doormaal, Adriaan C G M Van Es, Wim H Van Zwam, Bart J Emmer, Ludo F Beenen, Charles B L M Majoie, Nancy Buderer, Michelle A Detry, Anna Bosse, Todd L Graves, Christina Saunders, Lucas Elijovich, Ashutosh Jadhav, Mary Patterson, Hannah Slight, Kristine Below, Sami Al Kasab, Tesla Investigators

Faculty, Staff and Student Publications

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at …

Examining Management And Employees' Perceptions Of Occupational Heat Exposure And The Effectiveness Of A Heat Stress Prevention Intervention On Safety And Well-Being Among Natural Gas Construction Workers: A Qualitative Field-Based Study

Faculty, Staff and Student Publications

BACKGROUND: Numerous risk factors have been identified as significantly influencing outdoor workers' risk for heat stress and heat-related conditions, impacting their health, well-being, and productivity. However, the specific effects of these factors on construction workers' safety, health, and well-being remain under-researched. With climate change increasing temperatures, assessing heat stress among construction workers is imperative.

OBJECTIVE: To identify the barriers and facilitators influencing the safety of natural gas construction workers and evaluate an implemented heat stress intervention.

METHODS: In the summer of 2023, two semi-structured interviews and six focus groups were conducted with twenty-one stakeholders at a Texas natural gas construction …

Implementation Of Healthy Heart Ambassador To Improve Blood Pressure Control At Community Health Centers In Texas, Pierre Fwelo

Faculty, Staff and Student Publications

BACKGROUND: Hypertension is one of the most prevalent chronic diseases in the United States and can increase a person's risk of stroke and other cardiovascular complications. Yet only 1 in 4 people with high blood pressure in the United States have their blood pressure managed. To improve hypertension control, we supported 9 health centers in Texas with the implementation of the Healthy Heart Ambassador Blood Pressure Self-Monitoring (HHA) Program.

METHODS: We provided health center training using the HHA Program Facilitation Training Guide, recorded barriers to implementing the HHA program, and employed strategies to overcome those barriers.

RESULTS: There were 68 …

Applying Deep Learning With Convolutional Neural Networks To Laryngoscopic Imaging For Automated Segmentation And Classification Of Vocal Cord Leukoplakia, Lan Lan, Ying Zhang, Dan Lv, Xiao-Bo Zhou, Hui Yang

Faculty, Staff and Student Publications

Objectives: Vocal cord leukoplakia is clinically described as a white plaque or patch on the vocal cords observed during macroscopic examination, which does not take into account histological features or prognosis. A clinical challenge in managing vocal cord leukoplakia is to assess the potential malignant transformation of the lesion. This study aims to investigate the potential of deep learning (DL) for the simultaneous segmentation and classification of vocal cord leukoplakia using narrow band imaging (NBI) and white light imaging (WLI). The primary objective is to assess the model's accuracy in detecting and classifying lesions, comparing its performance in WLI and …

Ablation Of The Integrin Cd11b Mac-1 Limits Deleterious Responses To Traumatic Spinal Cord Injury And Improves Functional Recovery In Mice, Yun Li, Zhuofan Lei, Rodney M Ritzel, Junyun He, Simon Liu, Junfang Wu

Faculty, Staff and Student Publications

Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of

Sequence-To-Expression Approach To Identify Etiological Non-Coding Dna Variations In P53 And Cmyc-Driven Diseases

Faculty, Staff and Student Publications

Disease risk prediction based on genomic sequence and transcriptional profile can improve disease screening and prevention. Despite identifying many disease-associated DNA variants, distinguishing deleterious non-coding DNA variations remains poor for most common diseases. In this study, we designed in vitro experiments to uncover the significance of occupancy and competitive binding between P53 and cMYC on common target genes. Analyzing publicly available ChIP-seq data for P53 and cMYC in embryonic stem cells showed that ~344-366 regions are co-occupied, and on average, two cis-overlapping motifs (CisOMs) per region were identified, suggesting that co-occupancy is evolutionarily conserved. Using U2OS and Raji cells untreated …

The Saga Acetyltransferase Module Is Required For The Maintenance Of Maf And Myc Oncogenic Gene Expression Programs In Multiple Myeloma, Ying-Jiun C Chen, Govinal Badiger Bhaskara, Yue Lu, Kevin Lin, Sharon Y R Dent

Faculty, Staff and Student Publications

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of data sets in the Cancer Dependency Map Project revealed that many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA sequencing (RNA-seq), …

Humoral Immunity And Antibody Responses Against Diphtheria, Tetanus, And Pneumococcus After Immune Effector Cell Therapies: A Prospective Study, Georgios Angelidakis, Roy F Chemaly, Pranoti V Sahasrabhojane, Oscar Morado-Aramburo, Ying Jiang, Elizabeth Shpall, Preetesh Jain, Kris Michael Mahadeo, Fareed Khawaja, Peter Elhajj, Jennifer A Wargo, Robert R Jenq, Nadim J Ajami, Partow Kebriaei, Ella J Ariza-Heredia

Faculty, Staff and Student Publications

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3-6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, …

Rethinking Health Systems Responsiveness In Low- And Middle-Income Countries: Validation Study, Sameen Siddiqi

Faculty, Staff and Student Publications

BACKGROUND: Health systems responsiveness (HSR) is the ability of systems to respond to legitimate non-health expectations of the population. The concept of HSR by the World Health Organization (WHO) includes respect for dignity, individual autonomy, confidentiality, prompt attention to care, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. The WHO tool is applied globally to assess HSR in low, middle, and high-income countries.

OBJECTIVE: We have revised the conceptual framework of HSR following a rigorous systematic review and made it specific for low- and middle-income countries (L&MICs). This study is designed to …

Association Between Non-Injection Drug Use And Hepatitis C Infection Among Hiv-Negative Men Who Have Sex With Men, Alan G Nyitray

Faculty, Staff and Student Publications

Background: Prior research predominantly examined the association between HIV-positive men who have sex with men (MSM) or those using injection drugs and hepatitis C virus (HCV) infection. However, limited attention has been given to understanding the association among HIV-negative MSM who do not inject drugs. This gap leaves apportion of the population unexamined, potentially overlooking important factor that may contribute to the transmission and prevalence of HCV. This study aims to investigate the relationship between non-injection drug use and HCV infection in this population.

Methods: In this cross-sectional study, we analyzed data on 118 MSM who reported use of non-injection …

Loss Of P53 And Smad4 Induces Adenosquamous Subtype Pancreatic Cancer In The Absence Of An Oncogenic Kras Mutation, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Ignacio I Wistuba, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, J Ma, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment As A Therapeutic Target In A Mouse Model Of Lung Cancer, Sean-Luc Shanahan, Nikesh Kunder, Charles Inaku, Natalie B Hagan, Grace Gibbons, Gayathri Anandappa, Kristen E Pauken, Tyler Jacks, Jason M Schenkel

Faculty, Staff and Student Publications

Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer …

A Qualitative Study Of The Knowledge Of Metabolic Syndrome, Attitudes About Lifestyle Modifications, And Preferences For Lifestyle Interventions Among Patients With Cancer And Metabolic Syndrome, Natalia I Heredia, Aimee J Christie, Tamara E Lacourt, Zayd Adnan Razouki, Jessica P Hwang

Faculty, Staff and Student Publications

Metabolic syndrome is a group of disorders-hypertension, dyslipidemia, obesity, and insulin resistance-that together increase the risk of coronary heart disease, stroke, and diabetes. Although ~60% of cancer patients have metabolic syndrome, which increases their risk of mortality, oncology providers lack clear guidance about its management. The development of metabolic syndrome lifestyle interventions requires a better understanding of these patients' knowledge, attitudes, and intervention preferences in order to inform management. During 2022-2023, 19 adult cancer patients with metabolic syndrome engaged in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were analyzed using hybrid thematic analysis involving deductive and inductive …

Spatially Fractionated Grid Radiation Potentiates Immune-Mediated Tumor Control, Rebecca A Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J Caudell, Shari Pilon-Thomas, Heiko Enderling

Faculty, Staff and Student Publications

Background: Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through …

Predictive Value Of Follow-Up Infarct Volume On Functional Outcomes In Middle Cerebral Artery M2 Segment Vessel Occlusion Stroke Treated With Mechanical Thrombectomy, Kareem El Naamani, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT.

Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute …

Characterization Of Dna Damage Repair Pathway Utilization In High-Grade Serous Ovarian Cancers Yields Rational Therapeutic Approaches, Erika Nakatsuka, Lijun Tan, Brianna Cunneen, Caroline Foster, Yu Leo Lei

Faculty, Staff and Student Publications

While poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have improved the prognosis of ovarian high-grade serous carcinoma (HGSC) tumors that are homologous recombination (HR) deficient (HRD), new therapeutic strategies are needed for tumors that are HR proficient (HRP) because they demonstrate greater resistance to current treatments and thus have poorer clinical outcomes. Additionally, clinical precautionary statements regarding potential risks associated with PARPi, such as myelodysplastic syndrome, highlight the need for combinatorial approaches that can lessen the dose and duration of PARPi treatment to reduce toxicities. Here, we evaluated DNA double-strand damage repair pathways in HRD and HRP ovarian cancer cell lines …

Expanding The Crispr Base Editing Toolbox In Drosophila Melanogaster, Michael Clark, Christina Nguyen, Hung Nguyen, Aidan Tay, Samuel J Beach, Víctor López Del Amo

Faculty, Staff and Student Publications

CRISPR base editors can introduce point mutations into DNA precisely, and cytosine base editors (CBEs) catalyze C to T transitions. While CBEs have been thoroughly explored in cell culture and organisms such as mice, little is known about DNA base editing in insects. In this study, we evaluated germline editing rates of three different CBEs expressed under actin (ubiquitous) or nanos (germline) promoters utilizing Drosophila melanogaster. The original Rattus norvegicus-derived cytosine deaminase APOBEC1 (rAPO-1) displayed high base editing rates (~99%) with undetectable indel formation. Additionally, we show that base editors can be used for generating male sterility and female lethality. …

Bacteroides Ovatus Alleviates Dysbiotic Microbiota-Induced Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C Stinson, Mohamed A Jamal, Christopher A Sanchez, Jennifer L Karmouch, Chia-Chi Chang, Ivonne I Flores, Lauren K Mcdaniel, Alexandria N Brown, Rawan K El-Himri, Valerie A Chapa, Lin Tan, Bao Q Tran, Yao Xiao, Christopher Fan, Dung Pham, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Israel K Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y King, Robert A Britton, Pavan Reddy, Matthew C Wong, Nadim J Ajami, Jennifer A Wargo, Samuel Shelburne, Pablo C Okhuysen, Chen Liu, Stephanie W Fowler, Margaret E Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos Da Silva, Doris M Ponce, Jonathan U Peled, Marcel R M Van Den Brink, Christine B Peterson, Gabriela Rondon, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Philip L Lorenzi, Rohtesh S Mehta, Eric C Martens, Amin M Alousi, Robert R Jenq

Faculty, Staff and Student Publications

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects …

Batf Is A Major Driver Of Nk Cell Epigenetic Reprogramming And Dysfunction In Aml, Bijender Kumar, Anand Singh, Rafet Basar, Nadima Uprety, Ye Li, Ana Karen Nunez Cortes, Sunil Acharya, Hila Shaim, Anna C Xu, Manrong Wu, Emily Ensley, Dexing Fang, Pinaki P Banerjee, Luciana Melo Garcia, Silvia Tiberti, Paul Lin, Hind Rafei, Maliha Nuzhat Munir, Madison Moore, Mayra Shanley, Mayela Mendt, Lucila N Kerbauy, Bin Liu, Alexander Biederstädt, Elif Gokdemir, Susmita Ghosh, Kiran Kundu, Francia Reyes-Silva, Xin Ru Jiang, Xinhai Wan, April L Gilbert, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Patrick Zhang, Enli Liu, Luis Muniz-Feliciano, Gary M Deyter, Abhinav K Jain, Juan Jose Rodriguez-Sevilla, Simona Colla, Guillermo Garcia-Manero, Elizabeth J Shpall, Ken Chen, Hussein A Abbas, Kunal Rai, Katayoun Rezvani, May Daher

Faculty, Staff and Student Publications

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism and exhausted phenotype at the single cell transcriptomic and proteomic levels. In this study we identified that this dysfunction was mediated through a crosstalk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ integrin/TGF-β/SMAD pathway but, once established, was persistent due to profound epigenetic reprogramming. …

Use Of Web-Based Surveys To Collect Long-Term Pediatric Outcomes In Patients With Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation: Observational Study, Ramesha Papanna

Faculty, Staff and Student Publications

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost.

Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS.

Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during …

Targeting Prmt3 Impairs Methylation And Oligomerization Of Hsp60 To Boost Anti-Tumor Immunity By Activating Cgas/Sting Signaling, Yunxing Shi, Zongfeng Wu, Shaoru Liu, Dinglan Zuo, Yi Niu, Liang Qiao, Jiliang Qiu, Yunfei Yuan, Guocan Wang, Binkui Li

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protein arginine methyltransferase 3 (PRMT3) as a driver for immunotherapy resistance in HCC. We show that PRMT3 expression is induced by ICB-activated T cells via an interferon-gamma (IFNγ)-STAT1 signaling pathway, and higher PRMT3 expression levels correlate with reduced numbers of tumor-infiltrating CD8+ T cells and poorer response to ICB. Genetic depletion or pharmacological inhibition of PRMT3 elicits an influx of T cells into tumors and reduces tumor size in HCC mouse models. Mechanistically, …

A Multivariate To Multivariate Approach For Voxel-Wise Genome-Wide Association Analysis, L Elliot Hong

Faculty, Staff and Student Publications

The joint analysis of imaging-genetics data facilitates the systematic investigation of genetic effects on brain structures and functions with spatial specificity. We focus on voxel-wise genome-wide association analysis, which may involve trillions of single nucleotide polymorphism (SNP)-voxel pairs. We attempt to identify underlying organized association patterns of SNP-voxel pairs and understand the polygenic and pleiotropic networks on brain imaging traits. We propose a bi-clique graph structure (ie, a set of SNPs highly correlated with a cluster of voxels) for the systematic association pattern. Next, we develop computational strategies to detect latent SNP-voxel bi-cliques and an inference model for statistical testing. …

A Smart Water Bottle And Companion App (Hidratespark 3) To Improve Bladder-Filling Compliance In Patients With Prostate Cancer Receiving Radiotherapy: Nonrandomized Trial Of Feasibility And Acceptability, Miguel Noy, Matthew Abramowitz, Raphael Yechieli, Alan Pollack, Alan Dal Pra

Faculty, Staff and Student Publications

Background: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE).

Objective: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE.

Methods: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both …

Genome-Wide Association Study Meta-Analysis Of Neurofilament Light (Nfl) Levels In Blood Reveals Novel Loci Related To Neurodegeneration, Marisol Herrera-Rivero, Gennady Roshchupkin, Edith Hofer, Mark Logue, W T Longstreth, Rui Xia, Vincent Bouteloup, Thomas Mosley, Lenore J Launer, Michael Khalil, Jens Kuhle, Robert A Rissman, Genevieve Chene, Carole Dufouil, Luc Djoussé, Michael J Lyons, Kenneth J Mukamal, William S Kremen, Reinhold Schmidt, Stephanie Debette, Monique M B Breteler, Klaus Berger, Qiong Yang, Sudha Seshadri, N Ahmad Aziz, Mohsen Ghanbari, M Arfan Ikram

Faculty, Staff and Student Publications

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify …

Long-Term Longitudinal Analysis Of 4,187 Participants Reveals Insights Into Determinants Of Clonal Hematopoiesis, Whitney E Hornsby, Art Schuermans, Michael C Honigberg, Alexander G Bick, Peter Libby, Benjamin L Ebert, Christie M Ballantyne, Pradeep Natarajan

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CHIP. Splicing factor genes (SF3B1, SRSF2, U2AF1, and ZRSR2) and TET2 CHIP grow significantly faster than DNMT3A non-R882 clones. We find that age at baseline and sex significantly …