Digital Commons Network^™

Environmental Drivers Of Dispersal In Black-And-White Ruffed Lemurs (Varecia Variegata), Amanda Mancini

Dissertations, Theses, and Capstone Projects

Dispersal is a fundamental aspect of primates’ lives, influencing population connectivity through gene flow, driving community structure and assembly, and having important consequences for adaptation and speciation. Primates disperse within an environmental context, with both intervening and local environmental factors affecting the motivation, capacity, timing, and success of dispersal at all phases. Direct evaluations of primate dispersal are challenging given the rarity of dispersal events and the large distances that animals often settle from their departure site, therefore indirect measures– such as the use of population genetic data– are more common.

The field of landscape genetics enables researchers to combine …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

Synthesis And Analysis Of Novel Troponoid-Based Chemical Probes, Alex Berkowitz

Dissertations, Theses, and Capstone Projects

Troponoids are a class of non-benzenoid aromatic species featuring a cycloheptatrienone ring and varying degrees of oxygenation. These scaffolds have proven ubiquitous amongst natural products, and have displayed promise as therapeutic agents against a variety of diseases. Herein, we will describe our efforts towards furthering troponoids as potential pharmaceuticals. In Chapter 1, we outline a kojic acid-derived oxidopyrylium cycloaddition/ring-opening method developed in our lab to generate ahydroxytropolones (aHTs). This route was successfully adapted to synthesize a small library of lipophilic aHTs that were proven to be effective against herpes simplex virus-1 (HSV-1) replication, while providing further insight into the mechanism …

The Devil Is In The Details: Witchcraft Materiality And Systems Of Belief In Early Modern France, Ryan Evelyn

Dissertations, Theses, and Capstone Projects

My approach to the early modern French witch figure, as defined by their materiality, considers the representation of things, objects, and substances in texts. It was inspired by the surge in material culture studies, whose genesis in the 1980s and 1990s spurred theoretical approaches to (re)considering human interactions with objects, the way in which materials can be manipulated to serve various ends, and which objects were deemed culturally significant. I employ this approach to a (re)assessment of the witch figure as illustrated in demonologies, medical texts, and imaginative literature as early as the 14^th century spanning into the early …

Beam-Based Target Alignment For Mu2e, Helenka Casler

Dissertations, Theses, and Capstone Projects

The Mu2e Experiment is a precision experiment at Fermi National Accelerator Laboratory, searching for charged lepton flavor violation (CLFV) in the conversion of a muon to an electron in the presence of an atomic nucleus. In order to achieve the expected single-event sensitivity of 3 × 10^-17 , Mu2e will require an intense muon beam, generated via pion decay. These pions are the product of a proton beam striking a radiatively-cooled tungsten target. In order to maximize pion production and prevent target failure, the beam will have to be aligned with the target center to within 0.5 mm. The …

Incarceration-Related Stigma And Caring Self-Efficacy Among Long-Term Care Nurses, Sandra D. Langston

Dissertations, Theses, and Capstone Projects

Background: A silver tsunami is occurring in U.S. prisons because of an unprecedented increase in the older population. Prisons are structurally ill-suited to care for this population and financially burdened with providing the necessary medical and nursing care. States have enacted legislation to afford justice-involved persons parole to manage chronic conditions in community-based long-term care (LTC) facilities. Changes in Medicaid regulations provide a seamless transition from prison to community long-term care for this population. However, it is not known if the stigma of justice involvement impacts the perception of long-term nurses concerning this population.

Aims/Purpose: This study examined the effects …

Quantifying Psychostimulant-Induced Sensitization Effects On Dopamine And Acetylcholine Release Across Different Timescales, Georg Lange

Dissertations, Theses, and Capstone Projects

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of …

Assessment Of Efficacy And Mechanism Of Resistance To Soil-Applied Ppo Inhibitors In Amaranthus Palmeri, Gulab Rangani, Aimone Perri, Reiofeli A. Salas-Perez, Jens Lerchl, Srikanth Kumar Karaikal, Juan Camilo Velásquez, Nilda Roma-Burgos

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Resistance to protoporphyrinogen oxidase (PPO) inhibitors in Palmer amaranth is a major concern, given the high selection pressure and increasing number of populations with reduced sensitivity to PPO herbicides in the US. We evaluated the effect of five soil-applied herbicides on Palmer amaranth (Amaranthus palmeri S. Wats.) populations collected in 2014 and 2015 in Arkansas, USA. Soil-applied saflufenacil, sulfentrazone, and flumioxazin reduced the seedling emergence 91–100%; however, fomesafen and oxyfluorfen showed reduced (63–90%) efficacy on some populations. Target-site mutation (TSM) is the major mechanism of resistance to PPO herbicides; therefore, six populations showing resistance to soil-applied fomesafen were selected for …

Trolley Problems, Private Necessity, And The Duty To Rescue, Laura A. Heymann

Faculty Publications

Laidlaw v. Sage is generally, at best, an oddity in Torts casebooks today. A case that captured the imagination of New York newspaper readers at the time, Laidlaw involved an explosion that, William Laidlaw argued, the wealthy Russell Sage survived only because, at the last moment, he pulled Laidlaw in front of him to absorb the brunt of the blast. As taught in Torts classrooms, Laidlaw is either a case about the intent requirement for battery or a case about causation. But the case, assuming the plaintiff’s story was true, also provides an interesting window into what would seem to …

How Prophet Muhammad(Saw)Took Care Of His Health, Anat Matimu

Halal Insight

No abstract provided.

Origin And Evolution Of Marsupial-Specific Imprinting Clusters Through Lineage-Specific Gene Duplications And Acquisition Of Promoter Differential Methylation, Wenqi Cao, Kory C. Douglas, Paul B. Samollow, John Vandeberg, Xu Wang, Andrew G. Clark

School of Medicine Publications

Genomic imprinting is a parent-of-origin-specific expression phenomenon that plays fundamental roles in many biological processes. In animals, imprinting is only observed in therian mammals, with ∼200 imprinted genes known in humans and mice. The imprinting pattern in marsupials has been minimally investigated by examining orthologs to known eutherian imprinted genes. To identify marsupial-specific imprinting in an unbiased way, we performed RNA-seq studies on samples of fetal brain and placenta from the reciprocal cross progeny of two laboratory opossum stocks. We inferred allele-specific expression for >3,000 expressed genes and discovered/validated 13 imprinted genes, including three previously known imprinted genes, Igf2r, Peg10, …

A Case Report Of Subacute Combined Degeneration Due To Nitrous Oxide-Induced Vitamin B12 Deficiency, Jorge Nadal Bosch, Javier Malcolm, Mario Moya, Michael Menowsky, Roberto A. Cruz

School of Medicine Publications

Nitrous oxide, also known as “laughing gas,” is a naturally occurring gas that is colorless, odorless, nonflammable, and nontoxic. It has been used as an inhalant anesthetic in the medical field for more than 150 years for dental and surgical procedures. Due to its wide availability and ability to cause euphoria, its recreational use is on the rise. We present a case of subacute combined degeneration (SCD) due to nitrous oxide-induced vitamin B12 deficiency. The patient presented with bilateral lower extremity paresthesia, weakness, and ataxic gait. The patient was found to have vitamin B12 deficiency. An MRI of the cervical …

Effortful Control Moderates The Relation Between Negative Emotionality And Child Anxiety And Depressive Symptom Severity In Children With Anxiety Disorders, Elizabeth M Raines, Andres G Viana, Erika S Trent, Haley E Conroy, Karina Silva, Michael J Zvolensky, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

The present study investigated the interactive effect of reactive (negative emotionality) and regulatory (effortful control) aspects of temperament in the prediction of child anxiety and depressive symptoms. Clinically anxious children and their mothers completed a battery of questionnaires that included self- and mother-ratings of child effortful control, negative emotionality, anxiety, and depressive symptoms. Multiple regression analyses were conducted to examine the moderating effect of effortful control on the relation between negative emotionality and child anxiety and depressive symptom severity. The interaction between negative emotionality and effortful control was statistically significant and simple slopes revealed that as effortful control increased, the …

Cultural Factors Associated With Human Trafficking Of Girls And Women In Northern Tanzania: The Case Of Arusha Region, Rehema John Magesa

Dignity: A Journal of Analysis of Exploitation and Violence

Human trafficking is persistent in many regions of Tanzania despite different efforts to reduce the practice by the Government and other stakeholders. Girls and young women are more affected by this practice in violation of their human rights than men and boys. This study explored the cultural factors attributing to the trafficking of girls and women in Northern Tanzania. The study involved 400 girls and young women for a quantitative and qualitative study on cultural determinants of human trafficking. The study found the following cultural practices pushed girls and women towards situations in which they could be trafficked: female genital …

The Process Of Sexual Misconduct By Male Teachers And Staff In K-12 Institutions, Mollee Steely Smith

Dignity: A Journal of Analysis of Exploitation and Violence

Despite the increased media attention of teachers who engage in sexual misconduct with their students, research on such incidents remains limited, specifically on how these incidents are initiated and evolve. The purpose of the current study was to examine the nature of sexual abuse incidents by K-12 teachers who engaged in sexual misconduct with students by focusing on the onset, progression, and conclusion of these cases. Data included 10 secondary narrative interviews with male sex offenders who used their position as school employees to target and engage in sexual misconduct with their students in 2014 in a southern state. All …

Hentai And The Pornification Of Childhood: How The Porn Industry Just Made The Case For Regulation, Gail Dines, Mandy Sanchez

Dignity: A Journal of Analysis of Exploitation and Violence

One of the most popular genres of online pornography today is hentai, sexualized animation, and cartoons in the style of Japanese anime. Data from Pornhub, the world’s best-known pornography website, as well as a recent report from a British regulatory agency and our research, show that much of hentai appeals to children and depicts child-like characters engaged in sexual violence. In almost every instance, this violence targets female characters. Hentai, we show, encourages adults to see minors, especially girls, as legitimate targets of sexual violence. Until the day when these depictions of sexual violence are eradicated, we call for three …

How And Why Is Context Important In Leadership?, Burak Oc, Joseph A. Carpini

Research Collection Lee Kong Chian School Of Business

Leadership can be defined as a goal-influence process that occurs between a leader and a follower, groups of followers, or institutions that directs effort towards the achievement of a shared objective (Antonakis & Day, 2018, p. 5). From this definition, we can distil four key elements of leadership: a) leaders, b) followers, c) influence and d) goals, motivation and performance. While leaders and followers are the main actors of leadership processes, how they influence each other has implications for group goals. However, most leadership research focuses on leaders, largely treating them as the sole driver of organisation success or failure …

Automated Field-In-Field Whole Brain Radiotherapy Planning, Kai Huang, Soleil Hernandez, Chenyang Wang, Callistus Nguyen, Tina Marie Briere, Laurence Court

Faculty, Staff and Student Publications

PURPOSE: We developed and tested an automatic field-in-field (FIF) solution for whole-brain radiotherapy (WBRT) planning that creates a homogeneous dose distribution by minimizing hotspots, resulting in clinically acceptable plans.

METHODS: A configurable auto-planning algorithm was developed to automatically generate FIF WBRT plans independent of the treatment planning system. Configurable parameters include the definition of hotspots, target volume, maximum number of subfields, and minimum number of monitor units per field. This algorithm iteratively identifies a hotspot, creates two opposing subfields, calculates the dose, and optimizes the beam weight based on user-configured constraints of dose-volume histogram coverage and least-squared cost functions. The …

The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer

Faculty, Staff and Student Publications

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral …

Adjuvant 5-Fluorouracil/Leucovorin, Capecitabine, And Oxaliplatin-Related Regimens For Stage Ii/Iii Colon Cancer Patients 66 Years Or Older, Emily Jones, Zhigang Duan, Thinh T Nguyen, Sharon H Giordano, Hui Zhao

Faculty, Staff and Student Publications

Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FU/LV), capecitabine, and adding oxaliplatin to 5-FU/LV or capecitabine (FLOX/OX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used …

Optimized Decision Support For Selection Of Transoral Robotic Surgery Or (Chemo)Radiation Therapy Based On Posttreatment Swallowing Toxicity, Mehdi Hemmati, Carly Barbon, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Ryan P Goepfert, Katherine A Hutcheson, Andrew J Schaefer, Clifton D Fuller, Md Anderson Head And Neck Cancer Symptom Working Group Affiliations Expand

Faculty, Staff and Student Publications

BACKGROUND: A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors.

METHODS: A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Inmaculada De La Torre, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Luis Fayad, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Liang-Chun Shih

Faculty, Staff and Student Publications

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The …

Structural Basis For Transcription Factor Zbtb7a Recognition Of Dna And Effects Of Zbtb7a Somatic Mutations That Occur In Human Acute Myeloid Leukemia, Ren Ren, John R Horton, Qin Chen, Jie Yang, Bin Liu, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to …

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …

Superior Verbal Learning And Memory In Pediatric Brain Tumor Survivors Treated With Proton Versus Photon Radiotherapy, Lisa E Mash, Lisa S Kahalley, M Fatih Okcu, David R Grosshans, Arnold C Paulino, Luz De Leon, Nilesh Desai, Zili D Chu, William E Whitehead, Murali Chintagumpala, Kimberly P Raghubar

Faculty, Staff and Student Publications

OBJECTIVE: Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers lower doses of radiation to healthy brain tissue. PRT has been associated with improved long-term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory.

METHOD: Survivors of pediatric brain tumor treated with either XRT (

RESULTS: Overall, patients receiving PRT demonstrated superior verbal learning and recall compared to those treated with XRT. Encoding and retrieval deficits were more common in the XRT group than the PRT …

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …

E Pluribus Unum: Prospective Acceptability Benchmarking From The Contouring Collaborative For Consensus In Radiation Oncology Crowdsourced Initiative For Multiobserver Segmentation, Diana Lin, Kareem A Wahid, Benjamin E Nelms, Renjie He, Mohammed A Naser, Michael V Sherer, Abdallah S R Mohamed, Michael Cislo, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Purpose: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement.

Approach: Participants who contoured ≥1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. …

Cotargeting Of Btk And Malt1 Overcomes Resistance To Btk Inhibitors In Mantle Cell Lymphoma, Vivian Changying Jiang, Yang Liu, Junwei Lian, Shengjian Huang, Alexa Jordan, Ruitao Lin, Joseph Mcintosh, Yijing Li, Yuxuan Che, Zhihong Chen, Jovanny Vargas, Maria Badillo, John Nelson Bigcal, Heng-Huan Lee, Wei Wang, Yixin Yao, Lei Nie, Christopher R Flowers, Michael Wang

Faculty, Staff and Student Publications

Bruton's tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11-knockout cells showed antitumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK/CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout …