Digital Commons Network^™

Clinical Outcomes And Differential Effects Of Pi3k Pathway Mutation In Obese Versus Non-Obese Patients With Cervical Cancer, Perry Grigsby, Adnan Elhammali, Fiona Ruiz, Stephanie Markovina, Michael D. Mclellan, Christopher A. Miller, Anupama Chundury, Ngoc-Anh L. Ta, Ramachandran Rashmi, John D. Pfeifer, Robert S. Fulton, Todd Dewees, Julie K. Schwarz

Open Access Publications

No abstract provided.

Radionuclides Transform Chemotherapeutics Into Phototherapeutics For Precise Treatment Of Disseminated Cancer, Nalinikanth Kotagiri, Matthew L. Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, Lemoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F. Dipersio, Samuel Achilefu

Open Access Publications

No abstract provided.

Toxic Alcohols, Jeffrey A. Kraut, Michael E. Mullins

Open Access Publications

No abstract provided.

Abnormal Microglia And Enhanced Inflammation-Related Gene Transcription In Mice With Conditional Deletion Of Ctcf In Camk2a-Cre-Expressing Neurons, Bryan E. Mcgill, Ruteja A. Barve, Susan E. Maloney, Amy Strickland, Nicholas Rensing, Peter L. Wang, Michael Wong, Richard Head, David F. Wozniak, Jeffrey Milbrandt

Open Access Publications

No abstract provided.

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy, A. M. Connolly, Et Al

Open Access Publications

No abstract provided.

Local Sequence Features That Influence Ap-1 Cis-Regulatory Activity, Hemangi G. Chaudhari, Barak A. Cohen

Open Access Publications

No abstract provided.

Fourier Transform Infrared Microscopy Enables Guidance Of Automated Mass Spectrometry Imaging To Predefined Tissue Morphologies, Jan-Hinrich Rabe, Denis A. Sammour, Sandra Schulz, Bogdan Munteanu, Martina Ott, Katharina Ochs, Peter Hohenberger, Alexander Marx, Michael Platten, Christiane A. Opitz, Daniel S. Ory, Carsten Hopf

Open Access Publications

No abstract provided.

Past Trauma And Future Choices: Differences In Discounting In Low-Income, Urban African Americans, Carissa Van Den Berk-Clark, Joel Myerson, Leonard Green, Richard A. Grucza

Open Access Publications

No abstract provided.

Compact, Multi-Exposure Speckle Contrast Optical Spectroscopy (Scos) Device For Measuring Deep Tissue Blood Flow, Tanja Dragojević, Joseph L. Hollmann, Davide Tamborini, Davide Portaluppi, Mauro Buttafava, Joseph P. Culver, Federica Villa, Turgut Durduran

Open Access Publications

No abstract provided.

Learning A Local-Variable Model Of Aromatic And Conjugated Systems, Matthew K. Matlock, Na Le Dang, S. Joshua Swamidass

Open Access Publications

No abstract provided.

A Case Of Acute Myeloid Leukemia With Promyelocytic Features Characterized By Expression Of A Novel Rarg-Cpsf6 Fusion, Christopher A. Miller, Christopher Tricarico, Zachary L. Skidmore, Geoffrey L. Uy, Yi-Shan Lee, Anjum Hassan, Michelle D. O'Laughlin, Heather Schmidt, Ling Tian, Eric J. Duncavage, Malachi Griffith, Obi L. Griffith, John S. Welch, Lukas D. Wartman

Open Access Publications

No abstract provided.

Left Atrial Structure And Function In Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With And Without Left Ventricular Hypertrophy, Hoshang Farhad, Sara B Seidelmann, Davis Vigneault, Siddique A Abbasi, Eunice Yang, Sharlene M Day, Steven D Colan, Mark W Russell, Jeffrey Towbin, Mark V Sherrid, Charles E Canter, Ling Shi, Michael Jerosch-Herold, David A Bluemke, Carolyn Ho, Tomas G Neilan

Open Access Publications

BACKGROUND: Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH).

METHOD: Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n = 34), preclinical mutation carriers without HCM (n = 24) and healthy, familial controls (n = 15).

RESULTS: LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was …

Pacritinib To Inhibit Jak/Stat Signaling In Refractory Metastatic Colon And Rectal Cancer, Thomas Regenbogen, Ling Chen, Kathryn Trinkaus, Andrea Wang-Gillam, Benjamin R. Tan, Manik Amin, Katrina S. Pedersen, Haeseong Park, Rama Suresh, Kian-Huat Lim, Emily Ratchford, Amberly Brown, A Craig Lockhart

Open Access Publications

Background: Treatment options for patients with refractory colorectal cancer are limited and typically provide a chance of only modest benefit. The goal of this study was to evaluate the benefit of inhibiting the JAK/STAT inflammatory pathway with single agent pacritinib in patients with metastatic refractory colorectal adenocarcinoma.

Methods: A single arm institutional trial was initiated and enrolled patients with metastatic colorectal cancer refractory to at least two standard lines of treatment. Pacritinib 400 mg daily was administered orally continuously in 28 day cycles.

Results: The trial was discontinued prior to reaching the planned accrual due to an FDA hold on …

B Cell-Derived Il-4 Acts On Podocytes To Induce Proteinuria And Foot Process Effacement, Alfred Hj Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, Andrey S. Shaw

Open Access Publications

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role in B cells in human disease than previously recognized. In some of these diseases, such as the minimal change disease subtype of nephrotic syndrome, pathogenic antibodies and immune complexes are not involved. We hypothesized that B cells, activated in the kidney, might produce cytokines capable of directly inducing cell injury and proteinuria. To directly test our hypothesis, we targeted a model antigen to the kidney glomerulus and showed that transfer of antigen-specific B cells could induce glomerular injury and proteinuria. …

Cerebrospinal Fluid And Blood Biomarkers For Neurodegenerative Dementias: An Update Of The Consensus Of The Task Force On Biological Markers In Psychiatry Of The World Federation Of Societies Of Biological Psychiatry, Piotr Lewczuk, Anne M. Fagan, Brian A. Gordon, Et Al

Open Access Publications

No abstract provided.

Whole Tumor Rna-Sequencing And Deconvolution Reveal A Clinically-Prognostic Pten/Pi3k-Regulated Glioma Transcriptional Signature, Yuan Pan, Erin C. Bush, Joseph A. Toonen, Yu Ma, Anne C. Solga, Peter A. Sims, David H. Gutmann

Open Access Publications

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance …

Alx Receptor Ligands Define A Biochemical Endotype For Severe Asthma, Isabell Ricklefs, Mario Castro, Andrea M. Coverstone, Et Al

Open Access Publications

BACKGROUND: In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA).

METHODS: ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] …

Pediatric And Adult Dilated Cardiomyopathy Represent Distinct Pathological Entities, Meghna D. Patel, Jayaram Mohan, Caralin Schneider, Geetika Bajpai, Enkhsaikhan Purevjav, Charles E. Canter, Jeffrey Towbin, Andrea Bredemeyer, Kory J. Lavine

Open Access Publications

Pediatric dilated cardiomyopathy (DCM) is the most common indication for heart transplantation in children. Despite similar genetic etiologies, medications routinely used in adult heart failure patients do not improve outcomes in the pediatric population. The mechanistic basis for these observations is unknown. We hypothesized that pediatric and adult DCM comprise distinct pathological entities, in that children do not undergo adverse remodeling, the target of adult heart failure therapies. To test this hypothesis, we examined LV specimens obtained from pediatric and adult donor controls and DCM patients. Consistent with the established pathophysiology of adult heart failure, adults with DCM displayed marked …

Ca2+-Permeable Ampars Mediate Glutamatergic Transmission And Excitotoxic Damage At The Hair Cell Ribbon Synapse, Joy Y. Sebe, Soyoun Cho, Lavinia Sheets, Mark A. Rutherford, Henrique Von Gersdorff, David W. Raible

Open Access Publications

We report functional and structural evidence for GluA2-lacking Ca

Genomic Landscape And Evolution Of Metastatic Chromophobe Renal Cell Carcinoma, Jozefina Casuscelli, James J. Hsieh, Et Al

Open Access Publications

Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) and ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal losses can generate proteotoxic stress and compromise cellular proliferation, it is intriguing how chRCC, a tumor with extensive chromosome losses and a low number of somatic mutations, can develop lethal metastases. Genomic features distinguishing metastatic from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS), targeted ultradeep cancer gene sequencing, and chromosome analyses (FACETS, OncoScan, and FISH), was performed on 79 chRCC patients including 38 metastatic (M-chRCC) …

Early Detection Of Gastric Cancer Using Global, Genome-Wide And Irf4, Elmo1, Clip4 And Msc Dna Methylation In Endoscopic Biopsies, Francesca Pirini, Douglas E. Berg, Et Al

Open Access Publications

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project ("TCGA"). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a …

Promising Therapeutics Of Gastrointestinal Cancers In Clinical Trials, Lingling Du, Zheng Che, Andrea Wang-Gillam

Open Access Publications

Many novel therapeutics are being developed for patients with cancers along the gastrointestinal (GI) tract. These emerging agents are frequently classified by their biological targets such as tumor growth pathways, tumor metabolism, microenvironment, etc. Some agents targeting cancer growth pathways are based on existing clinically validated therapeutic targets, such as regorafenib for hepatocellular carcinoma (HCC), while other agents focus on newly identified targets, such as

The Improvedd Vte Risk Score: Incorporation Of D-Dimer Into The Improve Score To Improve Venous Thromboembolism Risk Stratification, C. Michael Gibson, Alex C. Spyropoulos, Alexander T. Cohen, Russell D. Hull, Samuel Z. Goldhaber, Roger D. Yusen, Adrian F. Hernandez, Serge Korjian, Yazan Daaboul, Alex Gold, Robert A. Harrington, Gerald Chi

Open Access Publications

No abstract provided.

Investigator And Independent Review Committee Exploratory Assessment And Verification Of Tumor Response In A Non-Hodgkin Lymphoma Study, Robert R Ford, Robert W Ford, Michael O'Neal, Brad S Kahl, Ling Chen, Mihaela Munteanu, Bruce D Cheson

Open Access Publications

Interpretation of endpoints (e.g. overall response rate) in clinical trials depends on the accurate and reliable measurement and identification of tumors. Regulatory agencies recommend blinded reviews of imaging data by independent review committees (IRCs). Differences in response outcomes that arise between IRCs and site investigators raise regulatory/sponsor concerns. Here, we evaluate discrepant tumor response assessments by the IRC and unblinded investigators (complete versus partial response, respectively) occurring in 52 (13% of 393 IRC-assessed responders) of 447 enrolled patients with treatment-naïve non-Hodgkin lymphoma from a randomized study. The IRC and investigators were 'likely correct' in 73% and 25% of cases, respectively …

Combination Epigenetic Therapy In Metastatic Colorectal Cancer (Mcrc) With Subcutaneous 5-Azacitidine And Entinostat: A Phase 2 Consortium/Stand Up 2 Cancer Study, Nilofer S. Azad, Douglas Adkins, Joel Picus, Richard Piekarz, Et Al

Open Access Publications

PURPOSE: Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies.

EXPERIMENTAL DESIGN: We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than …

Cholinergic, But Not Dopaminergic Or Noradrenergic, Enhancement Sharpens Visual Spatial Perception In Humans, Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L. Wallace, Mark D'Esposito, Michael A. Silver

Open Access Publications

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker …

Are There Multiple Kinds Of Episodic Memory? An Fmri Investigation Comparing Autobiographical And Recognition Memory Tasks, Hung-Yu Chen, Adrian W. Gilmore, Steven M. Nelson, Kathleen B. Mcdermott

Open Access Publications

What brain regions underlie retrieval from episodic memory? The bulk of research addressing this question with fMRI has relied upon recognition memory for materials encoded within the laboratory. Another, less dominant tradition has used autobiographical methods, whereby people recall events from their lifetime, often after being cued with words or pictures. The current study addresses how the neural substrates of successful memory retrieval differed as a function of the targeted memory when the experimental parameters were held constant in the two conditions (except for instructions). Human participants studied a set of scenes and then took two types of memory test …

Effective Antibiotic Conservation By Emergency Antimicrobial Stewardship During A Drug Shortage, Kevin Hsueh, Maria Reyes, Tamara Krekel, Ed Casabar, David J. Ritchie, S. Reza Jafarzadeh, Amanda J. Hays, Michael A. Lane, Michael J. Durkin

Open Access Publications

No abstract provided.

Plasma Rest: A Novel Candidate Biomarker Of Alzheimer's Disease Is Modified By Psychological Intervention In An At-Risk Population, N. J. Ashton, A. Hye, C. A. Leckey, A. R. Jones, A. Gardner, C. Elliott, J. L. Wetherell, E. J. Lenze, R. Killick, N. L. Marchant

Open Access Publications

No abstract provided.

An Efficient Platform For Astrocyte Differentiation From Human Induced Pluripotent Stem Cells, Julia Tcw, Minghui Wang, Anna A. Pimenova, Kathryn R. Bowles, Brigham J. Hartley, Emre Lacin, Saima I. Machlovi, Rawan Abdelaal, Celeste M. Karch, Hemali Phatnani, Paul A. Slesinger, Bin Zhang, Alison M. Goate, Kristen J. Brennand

Open Access Publications

No abstract provided.