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Federated Learning In Medicine: Facilitating Multi‑Institutional Collaborations Without Sharing Patient Data, Micah J. Sheller, Brandon Edwards, G. Anthony Reina, Jason Martin, Sarthak Pati, Aikaterini Kotrotsou, Mikhail Milchenko, Weilin Xu, Daniel Marcus, Rivka R. Colen, Spyridon Bakas Jan 2020

Federated Learning In Medicine: Facilitating Multi‑Institutional Collaborations Without Sharing Patient Data, Micah J. Sheller, Brandon Edwards, G. Anthony Reina, Jason Martin, Sarthak Pati, Aikaterini Kotrotsou, Mikhail Milchenko, Weilin Xu, Daniel Marcus, Rivka R. Colen, Spyridon Bakas

Open Access Publications

No abstract provided.


Focal Dynamic Thermal Imaging For Label‑Free High‑Resolution Characterization Of Materials And Tissue Heterogeneity, Christine M. O'Brien, Hongyu Meng, Leonid Shmuylovich, Julia Carpenter, Praneeth Gogineni, Haini Zhang, Kevin Bishop, Suman B. Mondal, Gail P. Sudlow, Cheryl Bethea, Clyde Bethea, Samuel Achilefu Jan 2020

Focal Dynamic Thermal Imaging For Label‑Free High‑Resolution Characterization Of Materials And Tissue Heterogeneity, Christine M. O'Brien, Hongyu Meng, Leonid Shmuylovich, Julia Carpenter, Praneeth Gogineni, Haini Zhang, Kevin Bishop, Suman B. Mondal, Gail P. Sudlow, Cheryl Bethea, Clyde Bethea, Samuel Achilefu

Open Access Publications

No abstract provided.


Aerococcus Urinae Isolated From Women With Lower Urinary Tract Symptoms: In Vitro Aggregation And Genome Analysis, Evann E Hilt, Catherine Putonti, Krystal Thomas-White, Amanda L Lewis, Karen L Visick, Nicole M Gilbert, Alan J Wolfe Jan 2020

Aerococcus Urinae Isolated From Women With Lower Urinary Tract Symptoms: In Vitro Aggregation And Genome Analysis, Evann E Hilt, Catherine Putonti, Krystal Thomas-White, Amanda L Lewis, Karen L Visick, Nicole M Gilbert, Alan J Wolfe

Open Access Publications

No abstract provided.


Mapping Of The Language Network With Deep Learning, Patrick Luckett, John J Lee, Ki Yun Park, Donna Dierker, Andy G S Daniel, Benjamin A Seitzman, Carl D Hacker, Beau M Ances, Eric C Leuthardt, Abraham Z Snyder, Joshua S Shimony Jan 2020

Mapping Of The Language Network With Deep Learning, Patrick Luckett, John J Lee, Ki Yun Park, Donna Dierker, Andy G S Daniel, Benjamin A Seitzman, Carl D Hacker, Beau M Ances, Eric C Leuthardt, Abraham Z Snyder, Joshua S Shimony

Open Access Publications

No abstract provided.


Competitive Tight-Binding Inhibition Of Vkorc1 Underlies Warfarin Dosage Variation And Antidotal Efficacy, Shuang Li, Shixuan Liu, Xiaoran Roger Liu, Mengru Mira Zhang, Weikai Li Jan 2020

Competitive Tight-Binding Inhibition Of Vkorc1 Underlies Warfarin Dosage Variation And Antidotal Efficacy, Shuang Li, Shixuan Liu, Xiaoran Roger Liu, Mengru Mira Zhang, Weikai Li

Open Access Publications

No abstract provided.


Flynet 2.0: Drosophila Heart 3d (2d + Time) Segmentation In Optical Coherence Microscopy Images Using A Convolutional Long Short-Term Memory Neural Network, Zhao Dong, Jing Men, Zhiwen Yang, Jason Jerwick, Airong Li, Rudolph E Tanzi, Chao Zhou Jan 2020

Flynet 2.0: Drosophila Heart 3d (2d + Time) Segmentation In Optical Coherence Microscopy Images Using A Convolutional Long Short-Term Memory Neural Network, Zhao Dong, Jing Men, Zhiwen Yang, Jason Jerwick, Airong Li, Rudolph E Tanzi, Chao Zhou

Open Access Publications

A custom convolutional neural network (CNN) integrated with convolutional long short-term memory (LSTM) achieves accurate 3D (2D + time) segmentation in cross-sectional videos of the Drosophila heart acquired by an optical coherence microscopy (OCM) system. While our previous FlyNet 1.0 model utilized regular CNNs to extract 2D spatial information from individual video frames, convolutional LSTM, FlyNet 2.0, utilizes both spatial and temporal information to improve segmentation performance further. To train and test FlyNet 2.0, we used 100 datasets including 500,000 fly heart OCM images. OCM videos in three developmental stages and two heartbeat situations were segmented achieving an intersection over …


Targeting Unconventional Host Components For Vaccination-Induced Protection Against Tb, Elisa Nemes, Shabaana A Khader, Rosemary V Swanson, Willem A Hanekom Jan 2020

Targeting Unconventional Host Components For Vaccination-Induced Protection Against Tb, Elisa Nemes, Shabaana A Khader, Rosemary V Swanson, Willem A Hanekom

Open Access Publications

The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4


Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions, Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. Digruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston Jan 2020

Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions, Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. Digruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston

Open Access Publications

No abstract provided.


Enhancing The Anti-Tumour Activity Of 177lu-Dota-Octreotate Radionuclide Therapy In Somatostatin Receptor-2 Expressing Tumour Models By Targeting Parp, Carleen Cullinane, Kelly Waldeck, Laura Kirby, Buck E. Rogers, Peter Eu, Richard W. Tothill, Rodney J. Hicks Jan 2020

Enhancing The Anti-Tumour Activity Of 177lu-Dota-Octreotate Radionuclide Therapy In Somatostatin Receptor-2 Expressing Tumour Models By Targeting Parp, Carleen Cullinane, Kelly Waldeck, Laura Kirby, Buck E. Rogers, Peter Eu, Richard W. Tothill, Rodney J. Hicks

Open Access Publications

No abstract provided.


Actual Causes Of Death In Relation To Media, Policy, And Funding Attention: Examining Public Health Priorities, Meagan R Pilar, Amy A Eyler, Sarah Moreland-Russell, Ross C Brownson Jan 2020

Actual Causes Of Death In Relation To Media, Policy, And Funding Attention: Examining Public Health Priorities, Meagan R Pilar, Amy A Eyler, Sarah Moreland-Russell, Ross C Brownson

Open Access Publications

Despite numerous public health advancements over the last century, we continue to under-invest in prevention and public health efforts. As a result, one of the most challenging aspects of public health is prioritizing the use of limited resources. Building on the foundation of previous researchers, the goal of this exploratory study was to provide current estimates for the actual causes of death, media attention, policy focus, and research funding in the United States. In addition, we sought to calculate and compare media attention, policy attention, and research funding trends to better assess the nation's prioritization of health issues. Using a …


Mitofusin 2 Dysfunction And Disease In Mice And Men, Gerald W Dorn Ii Jan 2020

Mitofusin 2 Dysfunction And Disease In Mice And Men, Gerald W Dorn Ii

Open Access Publications

A causal relationship between Mitofusin (MFN) 2 gene mutations and the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2A (CMT2A) was described over 15 years ago. During the intervening period much has been learned about MFN2 functioning in mitochondrial fusion, calcium signaling, and quality control, and the consequences of these MFN2 activities on cell metabolism, fitness, and development. Nevertheless, the challenge of defining the central underlying mechanism(s) linking mitochondrial abnormalities to progressive dying-back of peripheral arm and leg nerves in CMT2A is largely unmet. Here, a different perspective of why, in humans, MFN2 dysfunction preferentially impacts peripheral nerves is provided based …


Feasibility And Validity Of A Low-Cost Racing Simulator In Driving Assessment After Stroke, Jonathan Tiu, Annie C Harmon, James D Stowe, Amen Zwa, Marc Kinnear, Latch Dimitrov, Tina Nolte, David B Carr Jan 2020

Feasibility And Validity Of A Low-Cost Racing Simulator In Driving Assessment After Stroke, Jonathan Tiu, Annie C Harmon, James D Stowe, Amen Zwa, Marc Kinnear, Latch Dimitrov, Tina Nolte, David B Carr

Open Access Publications

There is a myriad of methodologies to assess driving performance after a stroke. These include psychometric tests, driving simulation, questionnaires, and/or road tests. Research-based driving simulators have emerged as a safe, convenient way to assess driving performance after a stroke. Such traditional research simulators are useful in recreating street traffic scenarios, but are often expensive, with limited physics models and graphics rendering. In contrast, racing simulators developed for motorsport professionals and enthusiasts offer high levels of realism, run on consumer-grade hardware, and can provide rich telemetric data. However, most offer limited simulation of traffic scenarios. This pilot study compares the …


Safety And Efficacy Outcomes Of The Xen45 Gel Stent Use For Refractory Glaucoma: A Surgery Series From Surgeon Trainees At A Tertiary Teaching Hospital, Karen Hong, John Lind, Arsham Sheybani Jan 2020

Safety And Efficacy Outcomes Of The Xen45 Gel Stent Use For Refractory Glaucoma: A Surgery Series From Surgeon Trainees At A Tertiary Teaching Hospital, Karen Hong, John Lind, Arsham Sheybani

Open Access Publications

Background: To study the effect of an ab interno gelatin stent (XEN45 Gel Stent, Allergan Inc., Irvine, California, USA) on intraocular pressure (IOP) as placed by glaucoma fellowship trainees in eyes with refractory glaucoma.

Methods: A prospective noncomparative study at a tertiary training center on 28 unique eyes undergoing ab interno gelatin stent implantation by glaucoma fellowship trainees. Data was collected at baseline and postoperatively at day 1, week 1, and months 1, 3, 5, and 12. Primary outcome was mean IOP change. Secondary outcomes included change in number of glaucoma medication classes and visual acuity. Safety outcomes included needling …


The Transcription Factor Eb Reduces The Intraneuronal Accumulation Of The Beta-Secretase-Derived App Fragment C99 In Cellular And Mouse Alzheimer’S Disease Models, Anaïs Bécot, Raphaëlle Pardossi-Piquard, Alexandre Bourgeois, Eric Duplan, Qingli Xiao, Abhinav Diwan, Jin-Moo Lee, Inger Lauritzen, Frédéric Checler Jan 2020

The Transcription Factor Eb Reduces The Intraneuronal Accumulation Of The Beta-Secretase-Derived App Fragment C99 In Cellular And Mouse Alzheimer’S Disease Models, Anaïs Bécot, Raphaëlle Pardossi-Piquard, Alexandre Bourgeois, Eric Duplan, Qingli Xiao, Abhinav Diwan, Jin-Moo Lee, Inger Lauritzen, Frédéric Checler

Open Access Publications

No abstract provided.


Unmasking Intra-Tumoral Heterogeneity And Clonal Evolution In Nf1-Mpnst, Chang-In Moon, William Tompkins, Yuxi Wang, Abigail Godec, Xiaochun Zhang, Patrik Pipkorn, Christopher A Miller, Carina Dehner, Sonika Dahiya, Angela C Hirbe Jan 2020

Unmasking Intra-Tumoral Heterogeneity And Clonal Evolution In Nf1-Mpnst, Chang-In Moon, William Tompkins, Yuxi Wang, Abigail Godec, Xiaochun Zhang, Patrik Pipkorn, Christopher A Miller, Carina Dehner, Sonika Dahiya, Angela C Hirbe

Open Access Publications

Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%-13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones …


Performance Of A Multiplexed Amplicon-Based Next-Generation Sequencing Assay For Hla Typing, Chang Liu, Brian F. Duffy, Eric T. Weimer, Maureen C. Montgomery, Jo-Ellen Jennemann, Rachel Hill, Donna Phelan, Lindsay Lay, Bijal A. Parikh Jan 2020

Performance Of A Multiplexed Amplicon-Based Next-Generation Sequencing Assay For Hla Typing, Chang Liu, Brian F. Duffy, Eric T. Weimer, Maureen C. Montgomery, Jo-Ellen Jennemann, Rachel Hill, Donna Phelan, Lindsay Lay, Bijal A. Parikh

Open Access Publications

BACKGROUND: Next-generation sequencing (NGS) has enabled efficient high-resolution typing of human leukocyte antigen (HLA) genes with minimal ambiguity. Most commercially available assays amplify individual or subgroup of HLA genes by long-range PCR followed by library preparation and sequencing. The AllType assay simplifies the workflow by amplifying 11 transplant-relevant HLA genes in one PCR reaction. Here, we report the performance of this unique workflow evaluated using 218 genetically diverse samples.

METHODS: Five whole genes (HLA-A/B/C/DQA1/DPA1) and six near-whole genes (HLA-DRB1/DRB345/DQB1/DPB1; excluding exon 1 and part of intron 1) were amplified in a multiplexed, long-range PCR. Manual library preparation was performed per …


Association Of Ptsd Symptom Groups With Functional Impairment And Distress In Trauma-Exposed Disaster Survivors, Carol S North, Erin Van Enkevort, Barry A Hong, Alina M Surís Jan 2020

Association Of Ptsd Symptom Groups With Functional Impairment And Distress In Trauma-Exposed Disaster Survivors, Carol S North, Erin Van Enkevort, Barry A Hong, Alina M Surís

Open Access Publications

BACKGROUND: In the nearly a quarter of a century since the addition of the clinically significant distress/impairment criterion to the definition of PTSD in DSM-IV, little research has been done to examine the association of this criterion with symptom group criteria and with the numbing subgroup specifically. This study was conducted to examine these relationships in a large database of disaster survivors consistently studied across 12 different incidents of the full range of disaster typology.

METHODS: Analysis was conducted on a merged database representing 1187 trauma-exposed survivors of 12 different disasters studied systematically. DSM-IV-TR criteria for disaster-related PTSD were assessed …


A Murine Model Demonstrates Capsule-Independent Adaptive Immune Protection In Survivors Of Klebsiella Pneumoniae Respiratory Tract Infection, Joy Twentyman, Catherine Morffy Smith, Julia S Nims, Aubree A Dahler, David A Rosen Jan 2020

A Murine Model Demonstrates Capsule-Independent Adaptive Immune Protection In Survivors Of Klebsiella Pneumoniae Respiratory Tract Infection, Joy Twentyman, Catherine Morffy Smith, Julia S Nims, Aubree A Dahler, David A Rosen

Open Access Publications

No abstract provided.


Deployment Of Convalescent Plasma For The Prevention And Treatment Of Covid-19, Evan M Bloch, Brenda J Grossman, Jeffrey P Henderson, Et Al Jan 2020

Deployment Of Convalescent Plasma For The Prevention And Treatment Of Covid-19, Evan M Bloch, Brenda J Grossman, Jeffrey P Henderson, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis …


Antagonism Between Substitutions In Β-Lactamase Explains A Path Not Taken In The Evolution Of Bacterial Drug Resistance, Cameron A. Brown, Liya Hu, Zhizeng Sun, Meha P. Patel, Sukrit Singh, Justin R. Porter, Banumathi Sankaran, B. V. Venkataram Prasad, Gregory R. Bowman, Timothy Palzkill Jan 2020

Antagonism Between Substitutions In Β-Lactamase Explains A Path Not Taken In The Evolution Of Bacterial Drug Resistance, Cameron A. Brown, Liya Hu, Zhizeng Sun, Meha P. Patel, Sukrit Singh, Justin R. Porter, Banumathi Sankaran, B. V. Venkataram Prasad, Gregory R. Bowman, Timothy Palzkill

Open Access Publications

No abstract provided.


Accuracy Of Electromyometrial Imaging Of Uterine Contractions In Clinical Environment, Hui Wang, Wenjie Wu, Michael Talcott, Robert C Mckinstry, Pamela K Woodard, George A Macones, Alan L Schwartz, Phillip Cuculich, Alison G Cahill, Yong Wang Jan 2020

Accuracy Of Electromyometrial Imaging Of Uterine Contractions In Clinical Environment, Hui Wang, Wenjie Wu, Michael Talcott, Robert C Mckinstry, Pamela K Woodard, George A Macones, Alan L Schwartz, Phillip Cuculich, Alison G Cahill, Yong Wang

Open Access Publications

Clinically, uterine contractions are monitored with tocodynamometers or intrauterine pressure catheters. In the research setting, electromyography (EMG), which detects electrical activity of the uterus from a few electrodes on the abdomen, is feasible, can provide more accurate data than these other methods, and may be useful for predicting preterm birth. However, EMG lacks sufficient spatial resolution and coverage to reveal where uterine contractions originate, how they propagate, and whether preterm contractions differ between women who do and do not progress to preterm delivery. To address those limitations, electromyometrial imaging (EMMI) was recently developed and validated to non-invasively assess three-dimensional (3D) …


On Complement, Memory, And Microglia, Robyn S. Klein Jan 2020

On Complement, Memory, And Microglia, Robyn S. Klein

Open Access Publications

No abstract provided.


Experiences From The Missouri Antimicrobial Stewardship Collaborative: A Mixed Methods Study, Sena J Sayood, Chinmayi Venkatram, Jason G Newland, Hilary M Babcock, David K Warren, George Turabelidze, Virginia R Mckay, Erin C Rachmiel, Kate Peacock, Tracey Habrock-Bach, Kevin Hsueh, Michael J Durkin Jan 2020

Experiences From The Missouri Antimicrobial Stewardship Collaborative: A Mixed Methods Study, Sena J Sayood, Chinmayi Venkatram, Jason G Newland, Hilary M Babcock, David K Warren, George Turabelidze, Virginia R Mckay, Erin C Rachmiel, Kate Peacock, Tracey Habrock-Bach, Kevin Hsueh, Michael J Durkin

Open Access Publications

We performed a mixed-methods study to evaluate antimicrobial stewardship program (ASP) uptake and to assess variability of program implementation in Missouri hospitals. Despite increasing uptake of ASPs in Missouri, there is wide variability in both the scope and sophistication of these programs.


Feasibility And Safety Of Focused Ultrasound-Enabled Liquid Biopsy In The Brain Of A Porcine Model, Christopher Pham Pacia, Lifei Zhu, Yaoheng Yang, Yimei Yue, Arash Nazeri, H. Michael Gach, Michael R. Talcott, Eric C. Leuthardt, Hong Chen Jan 2020

Feasibility And Safety Of Focused Ultrasound-Enabled Liquid Biopsy In The Brain Of A Porcine Model, Christopher Pham Pacia, Lifei Zhu, Yaoheng Yang, Yimei Yue, Arash Nazeri, H. Michael Gach, Michael R. Talcott, Eric C. Leuthardt, Hong Chen

Open Access Publications

No abstract provided.


New Imaging Tools To Measure Nephron Number In Vivo: Opportunities For Developmental Nephrology, K M Bennett, E J Baldelomar, D Morozov, R L Chevalier, J R Charlton Jan 2020

New Imaging Tools To Measure Nephron Number In Vivo: Opportunities For Developmental Nephrology, K M Bennett, E J Baldelomar, D Morozov, R L Chevalier, J R Charlton

Open Access Publications

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.


A Prospective Study Of Weight Gain In Women Diagnosed With Early-Stage Invasive Breast Cancer, Ductal Carcinoma In Situ, And Women Without Breast Cancer, Christine C. Ekenga, Xiaoyan Wang, Maria Pérez, Mario Schootman, Donna B. Jeffe Jan 2020

A Prospective Study Of Weight Gain In Women Diagnosed With Early-Stage Invasive Breast Cancer, Ductal Carcinoma In Situ, And Women Without Breast Cancer, Christine C. Ekenga, Xiaoyan Wang, Maria Pérez, Mario Schootman, Donna B. Jeffe

Open Access Publications

No abstract provided.


Deep Learning Assessment Of Breast Terminal Duct Lobular Unit Involution: Towards Automated Prediction Of Breast Cancer Risk, Suzanne C. Wetstein, Ying Liu, Et Al. Jan 2020

Deep Learning Assessment Of Breast Terminal Duct Lobular Unit Involution: Towards Automated Prediction Of Breast Cancer Risk, Suzanne C. Wetstein, Ying Liu, Et Al.

Open Access Publications

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs. We developed a computational pathology solution to automatically capture TDLU involution measures. Whole slide images (WSIs) of benign breast biopsies were obtained from the Nurses' Health Study. A set of 92 WSIs was annotated for acini, TDLUs and adipose tissue to train deep convolutional neural network (CNN) models for detection of acini, and …


A Functional Role For Eicosanoid-Lysophospholipids In Activating Monocyte Signaling, Gao-Yuan Liu, Sung Ho Moon, Christopher M. Jenkins, Harold F. Sims, Shaoping Guan, Richard W. Gross Jan 2020

A Functional Role For Eicosanoid-Lysophospholipids In Activating Monocyte Signaling, Gao-Yuan Liu, Sung Ho Moon, Christopher M. Jenkins, Harold F. Sims, Shaoping Guan, Richard W. Gross

Open Access Publications

No abstract provided.


Comparing Transplant Outcomes In All Patients After Haploidentical With Ptcy Or Matched Unrelated Donor Transplantation, Monzr M. Al Malki, Francesca Ferraro, Armin Ghobadi, Et Al. Jan 2020

Comparing Transplant Outcomes In All Patients After Haploidentical With Ptcy Or Matched Unrelated Donor Transplantation, Monzr M. Al Malki, Francesca Ferraro, Armin Ghobadi, Et Al.

Open Access Publications

No abstract provided.


Tpl2 Enforces Ras-Induced Inflammatory Signaling And Is Activated By Point Mutations, Paarth B Dodhiawala, Namrata Khurana, Daoxiang Zhang, Yi Cheng, Lin Li, Qing Wei, Kuljeet Seehra, Hongmei Jiang, Patrick M Grierson, Andrea Wang-Gillam, Kian-Huat Lim Jan 2020

Tpl2 Enforces Ras-Induced Inflammatory Signaling And Is Activated By Point Mutations, Paarth B Dodhiawala, Namrata Khurana, Daoxiang Zhang, Yi Cheng, Lin Li, Qing Wei, Kuljeet Seehra, Hongmei Jiang, Patrick M Grierson, Andrea Wang-Gillam, Kian-Huat Lim

Open Access Publications

NF-κB transcription factors, driven by the IRAK/IKK cascade, confer treatment resistance in pancreatic ductal adenocarcinoma (PDAC), a cancer characterized by near-universal KRAS mutation. Through reverse-phase protein array and RNA sequencing we discovered that IRAK4 also contributes substantially to MAPK activation in KRAS-mutant PDAC. IRAK4 ablation completely blocked RAS-induced transformation of human and murine cells. Mechanistically, expression of mutant KRAS stimulated an inflammatory, autocrine IL-1β signaling loop that activated IRAK4 and the MAPK pathway. Downstream of IRAK4, we uncovered TPL2 (also known as MAP3K8 or COT) as the essential kinase that propels both MAPK and NF-κB cascades. Inhibition of TPL2 blocked …