Digital Commons Network^™

Expanding The Genetic Architecture Of Nicotine Dependence And Its Shared Genetics With Multiple Traits, Bryan C. Quach, Michael J. Bray, Pamela Madden, Laura J. Bierut, Nancy L. Saccone, Et Al.

Open Access Publications

No abstract provided.

Stretchable, Dynamic Covalent Polymers For Soft, Long-Lived Bioresorbable Electronic Stimulators Designed To Facilitate Neuromuscular Regeneration, Yeon Sik Choi, Ying Yan, Matthew R. Macewan, Wilson Z. Ray, Et Al.

Open Access Publications

No abstract provided.

Determining The Recommended Dose Of Pacritinib: Results From The Pac203 Dose-Finding Trial In Advanced Myelofibrosis, Aaron T. Gerds, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml, Jayakumar Vadakekolathu, Michael P. Rettig, John F. Dipersio, Et Al.

Open Access Publications

No abstract provided.

Structural Basis Of Chikungunya Virus Inhibition By Monoclonal Antibodies, Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok

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

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 …

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) …

Development Of A New Macrophage-Specifc Trap Mouse (Mactrap) And Definition Of The Renal Macrophage Translational Signature, Andreas Hofmeister, Maximilian C. Thomaßen, Sabrina Markert, André Marquardt, Mathieu Preußner, Martin Rußwurm, Ralph T. Schermuly, Ulrich Steinhoff, Hermann-Josef Gröne, Joachim Hoyer, Benjamin D. Humphreys, Ivica Grgic

Open Access Publications

No abstract provided.

Plasmacytoid Dendritic Cell Impairment In Metastatic Melanoma By Lactic Acidosis, Matilde Monti, Raffaella Vescovi, Francesca Consoli, Davide Farina, Daniele Moratto, Alfredo Berruti, Claudia Specchia, William Vermi

Open Access Publications

The introduction of targeted therapies and immunotherapies has significantly improved the outcome of metastatic melanoma (MM) patients. These approaches rely on immune functions for their anti-melanoma response. Plasmacytoid dendritic cells (pDCs) exhibit anti-tumor function by production of effector molecules, type I interferons (I-IFNs), and cytokines. Tissue and blood pDCs result compromised in MM, although these findings are still partially conflicting. This study reports that blood pDCs were dramatically depleted in MM, particularly in patients with high lactate dehydrogenase (LDH) and high tumor burden; the reduced pDC frequency was associated with poor overall survival. Circulating pDCs resulted also in significant impairment …

Distinct Neural Networks Associated With Obsession And Delusion: A Connectome-Wide Association Study, Tae Young Lee, Wi Hoon Jung, Yoo Bin Kwak, Youngwoo B Yoon, Junhee Lee, Minah Kim, Euitae Kim, Jun Soo Kwon

Open Access Publications

BACKGROUND: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS).

METHODS: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion …

Individualization Of Attention-Deficit/Hyperactivity Disorder Treatment: Pharmacotherapy Considerations By Age And Co-Occurring Conditions, Greg W Mattingly, Joshua Wilson, Leticia Ugarte, Paul Glaser

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient's age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges …

Non-Conventional Treatments For Conventional Chondrosarcoma, Varun Monga, Hariharasudan Mani, Angela Hirbe, Mohammed Milhem

Open Access Publications

Chondrosarcomas are the most common malignant tumors of the cartilage, are seen predominantly in adults, and have varied clinical behavior. The majority of them affect the medullary canal of long bones and pelvic bones. The prognosis of chondrosarcoma is closely related to histological grading; however, the grading is subject to interobserver variability. Conventional chondrosarcomas are overall considered to be chemotherapy- and radiation-resistant, resulting in limited treatment options. The majority of advanced conventional chondrosarcomas are treated with chemotherapy without any survival benefit. Recent studies have evaluated molecular genetic findings which have improved the understanding of chondrosarcoma biology. Newer therapeutic targets are …

Characteristics And Outcomes Among A Hospitalized Patient Cohort With Streptococcus Pneumoniae Infection, Scott T. Micek, James Simmons, Nicholas Hampton, Marin H. Kollef

Open Access Publications

No abstract provided.

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.

Structural Basis For Effector Protein Recognition By The Dot/Icm Type Ivb Coupling Protein Complex, Hyunmin Kim, Tomoko Kubori, Kohei Yamazaki, Mi-Jeong Kwak, Suk-Youl Park, Hiroki Nagai, Joseph P. Vogel, Byung-Ha Oh

Open Access Publications

No abstract provided.

Cathepsin S And Protease-Activated Receptor-2 Drive Alloimmunity And Immune Regulation In Kidney Allograft Rejection, Yutian Lei, Benjamin Ehle, Santhosh V Kumar, Susanne Müller, Solange Moll, Andrew F Malone, Benjamin D Humphreys, Joachim Andrassy, Hans-Joachim Anders

Open Access Publications

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes.

Come Together: Protein Assemblies, Aggregates And The Sarcostat At The Heart Of Cardiac Myocyte Homeostasis, Moydul Islam, Abhinav Diwan, Kartik Mani

Open Access Publications

Homeostasis in vertebrate systems is contingent on normal cardiac function. This, in turn, depends on intricate protein-based cellular machinery, both for contractile function, as well as, durability of cardiac myocytes. The cardiac small heat shock protein (csHsp) chaperone system, highlighted by αB-crystallin (CRYAB), a small heat shock protein (sHsp) that forms ∼3-5% of total cardiac mass, plays critical roles in maintaining proteostatic function via formation of self-assembled multimeric chaperones. In this work, we review these ancient proteins, from the evolutionarily preserved role of homologs in protists, fungi and invertebrate systems, as well as, the role of sHsps and chaperones in …

Prostate Cancer Theranostics - An Overview, Diane Abou, Nadia Benabdallah, Wen Jiang, Lu Peng, Hanwen Zhang, Alexandria Villmer, Mark S Longtine, Daniel L J Thorek

Open Access Publications

Metastatic prostate cancer is incurable, and novel methods to detect the disease earlier and to direct definitive treatment are needed. Molecularly specific tools to localize diagnostic and cytotoxic radionuclide payloads to cancer cells and the surrounding microenvironment are recognized as a critical component of new approaches to combat this disease. The implementation of theranostic approaches to characterize and personalize patient management is beginning to be realized for prostate cancer patients. This review article summarized clinically translated approaches to detect, characterize, and treat disease in this rapidly expanding field.

Harnessing Activin A Adjuvanticity To Promote Antibody Responses To Bg505 Hiv Envelope Trimers, Diane G Carnathan, Kirti Kaushik, Ali H Ellebedy, Chiamaka A Enemuo, Etse H Gebru, Pallavi Dhadvai, Mohammed Ata Ur Rasheed, Matthias G Pauthner, Gabriel Ozorowski, Rafi Ahmed, Dennis R Burton, Andrew B Ward, Guido Silvestri, Shane Crotty, Michela Locci

Open Access Publications

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Formation Of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated By Mycobacterium Tuberculosis Expressed Determinants, Micah D Dunlap, Oliver A Prince, Javier Rangel-Moreno, Kimberly A Thomas, Julia M Scordo, Jordi B Torrelles, Jeffery Cox, Adrie J C Steyn, Joaquín Zúñiga, Deepak Kaushal, Shabaana A Khader

Open Access Publications

No abstract provided.

Evidence-Based Guidelines For Managing Patients With Primary Er+ Her2− Breast Cancer Deferred From Surgery Due To The Covid-19 Pandemic, Mitch Dowsett, Cynthia X. Ma, Et Al.

Open Access Publications

No abstract provided.

Landscape Of Somatic Single Nucleotide Variants And Indels In Colorectal Cancer And Impact On Survival, Syed H. Zaidi, Yin Cao, Et Al.

Open Access Publications

No abstract provided.

Effects Of Early Life Exposure To Traffic-Related Air Pollution On Brain Development In Juvenile Sprague-Dawley Rats, Kelley T. Patten, Eduardo A. González, Anthony Valenzuela, Elizabeth Berg, Christopher Wallis, Joel R. Garbow, Jill L. Silverman, Keith J. Bein, Anthony S. Wexler, Pamela J. Lein

Open Access Publications

No abstract provided.

Evolution And Structure Of Clinically Relevant Gene Fusions In Multiple Myeloma, Steven M. Foltz, Qingsong Gao, Christopher J. Yoon, Hua Sun, Lijun Yao, Yize Li, Reyka G. Jayasinghe, Song Cao, Justin King, Daniel R. Kohnen, Mark A. Fiala, Li Ding, Ravi Vij

Open Access Publications

No abstract provided.

Using A Developmental Perspective To Examine The Moderating Effects Of Marriage On Heavy Episodic Drinking In A Young Adult Sample Enriched For Risk, Seung Bin Cho, Rebecca L Smith, Kathleen Bucholz, Grace Chan, Howard J Edenberg, Victor Hesselbrock, John Kramer, Vivia V Mccutcheon, John Nurnberger, Marc Schuckit, Yong Zang, Danielle M Dick, Jessica E Salvatore

Open Access Publications

Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED …

Residual Endotoxin Induces Primary Graft Dysfunction Through Ischemia/Reperfusion-Primed Alveolar Macrophages, Mahzad Akbarpour, Daniel Kreisel, Wenjun Li, Et Al

Open Access Publications

Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to the fatal syndrome of primary graft dysfunction (PGD) following lung transplantation. We report that bacterial endotoxin persists in human donor lungs after pathogen is cleared with antibiotics and is associated with neutrophil infiltration and PGD. In mouse models, depletion of tissue-resident alveolar macrophages (TRAMs) attenuated neutrophil recruitment in response to endotoxin as shown by compartmental staining and intravital imaging. Bone marrow chimeric mice revealed that neutrophils were recruited by TRAM through activation of TLR4 in a MyD88-dependent manner. Intriguingly, low levels of endotoxin, insufficient to cause donor …

Interleukin-15 Superagonist (N-803) Treatment Of Pml And Jcv In A Post–Allogeneic Hematopoietic Stem Cell Transplant Patient, Aabha Oza, Michael P. Rettig, Phil Powell, Kathryn O'Brien, David B. Clifford, Julie Ritchey, Leah Gehrs, Julia Hollaway, Eugene Major, Todd A. Fehniger, Christopher A. Miller, Patrick Soon-Shiong, Amy Rock, John F. Dipersio

Open Access Publications

No abstract provided.

Incipient Alcohol Use In Childhood: Early Alcohol Sipping And Its Relations With Psychopathology And Personality, Ashley L Watts, Phillip K Wood, Kristina M Jackson, Krista M Lisdahl, Mary M Heitzeg, Raul Gonzalez, Susan F Tapert, Deanna M Barch, Kenneth J Sher

Open Access Publications

Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a …

Preclinical Single Photon Emission Computed Tomography Of Alpha Particle-Emitting Radium-223, Diane S. Abou, Andrew Rittenbach, Ryan E. Tomlinson, Paige A. Finley, Benjamin Tsui, Brian W. Simons, Abhinav K. Jha, David Ulmert, Ryan C. Riddle, Daniel L. J. Thorek

Open Access Publications

No abstract provided.

Single-Cell Transcriptomic Analysis Identifies The Conversion Of Zebrafish Etv2-Deficient Vascular Progenitors Into Skeletal Muscle, Brendan Chestnut, Satish Casie Chetty, Andrew L. Koenig, Saulius Sumanas

Open Access Publications

No abstract provided.