Digital Commons Network^™

Dupilumab Improves Symptoms, Quality Of Life, And Productivity In Uncontrolled Persistent Asthma, Jonathan Corren, Mario Castro, Pascal Chanez, Leonardo Fabbri, Vijay N Joish, Nikhil Amin, Neil M H Graham, Vera Mastey, Adeline Abbé, Christine Taniou, Puneet Mahajan, Ariel Teper, Gianluca Pirozzi, Laurent Eckert

Open Access Publications

BACKGROUND: In a pivotal, phase 2b study (NCT01854047) in patients with uncontrolled persistent asthma, despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2 agonists, dupilumab improved lung function, reduced severe exacerbations, and showed an acceptable safety profile.

OBJECTIVE: To assess the impact of dupilumab on asthma control, symptoms, quality of life (QoL), and productivity.

METHODS: Data are shown for the intention-to-treat population receiving dupilumab 200/300 mg every 2 weeks (doses being assessed in phase 3; NCT02414854), or placebo. Predefined analyses of total scores were conducted at week 24 for the 5-item Asthma Control Questionnaire (ACQ-5), patient-reported morning/evening (AM/PM) asthma symptoms, Asthma …

Nanotherapy Targeting Nf-Κb Attenuates Acute Pain After Joint Injury, Huimin Yan, Xin Duan, Kelsey H Collins, Luke E Springer, Farshid Guilak, Samuel A Wickline, M Farooq Rai, Hua Pan, Christine T N Pham

Open Access Publications

Inflammation after joint injury leads to joint responses that result in eventual osteoarthritis development. Blockade of inflammation, by suppressing NF-κB expression, has been shown to reduce joint injury-induced chondrocyte apoptosis and reactive synovitis

Protocol For The Electroencephalography Guidance Of Anesthesia To Alleviate Geriatric Syndromes (Engages-Canada) Study: A Pragmatic, Randomized Clinical Trial, Alain Deschamps, Jordan Oberhaus, Angela Mickle, Arbi Ben Abdallah, Michael S Avidan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Validation Of A Commercial Antibody To Detect Endogenous Human Nicastrin By Immunoblot, Rosana A Mesa, Elisha D O Roberson

Open Access Publications

Nicastrin (NCSTN) is a transmembrane glycoprotein that is part of the gamma-secretase complex. Gamma-secretase is a protease complex that cleaves type-I single-pass transmembrane proteins. There are many potential substrates for this complex, including NOTCH receptors and amyloid precursor proteins (APP). There are a number of commercial antibodies to nicastrin, but they do not agree on expected peptide size. We confirmed the specificity of a C-terminal binding rabbit anti-human antibody from Sigma-Aldrich (#N1660) using wildtype HEK293 cells and HEK293 cells deleted for nicastrin. The wildtype cells showed a prominent band at approximately 110 kDa. We confirmed this larger than expected sized …

Management Of Adrenal Insufficiency Risk After Long-Term Systemic Glucocorticoid Therapy In Duchenne Muscular Dystrophy: Clinical Practice Recommendations, Sasigarn A. Bowden, Anne M. Connolly, Kathi Kinnett, Philip S. Zeitler

Open Access Publications

No abstract provided.

Associations Of Mitochondrial And Nuclear Mitochondrial Variants And Genes With Seven Metabolic Traits, Aldi T. Kraja, Charles Gu, Mary F. Feitosa, Shiow J. Lin, Lihua Wang, Mary J. Wojczynski, Ruteja A. Barve, Ping An, Thomas J. Baranski, E. Warwick Daw, Lisa De Las Fuentes, Latisha D. Love-Gregory, Christine Williams, Wei Yang, D. C. Rao, Victor G. Davila-Roman, Michael Province, Et Al

Open Access Publications

No abstract provided.

Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, And Outcomes, Ashwin A. Kamath, Daniel D. Friedman, S Hassan A. Akbari, Albert H. Kim, Yu Tao, Jinqin Luo, Eric C. Leuthardt

Open Access Publications

BACKGROUND: Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking.

OBJECTIVE: To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes.

METHODS: We performed a retrospective descriptive study of patients with histologically proven GBM …

Ctcf Variants In 39 Individuals With A Variable Neurodevelopmental Disorder Broaden The Mutational And Clinical Spectrum, Enrico D. H. Konrad, Marwan Shinawi, Emily Fassi, Et Al.

Open Access Publications

No abstract provided.

Syndemic Effects Of Hiv Risk Behaviours: Results From The Nhanes Study, L Smith, C Cao, X Zong, D T Mcdermott, S Stefanac, S Haider, S E Jackson, N Veronese, G F López-Sánchez, A Koyanagi, L Yang, I Grabovac

Open Access Publications

The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009-2010 to 2015-2016. We carried out weighted regression among young adults (20-39 years) and adults (40-59 years) separately. In total, 5230 men and 5794 women aged 20-59 years were included in the present analyses. In total, 0.8% men and 0.2% women were …

Recommendations And Alerting For Delirium Alleviation In Real-Time (Radar): Protocol For A Pilot Randomized Controlled Trial, Phillip E Vlisides, Jacqueline W Ragheb, Aleda Leis, Amanda Schoettinger, Kim Hickey, Amy Mckinney, Joseph Brooks, Mackenzie Zierau, Alexandra Norcott, Shirley Yang, Michael S Avidan, Lillian Min

Open Access Publications

No abstract provided.

Top 10 Research Priorities In Spatial Lifecourse Epidemiology, Peng Jia, Ross C. Brownson, Et Al.

Open Access Publications

No abstract provided.

Pain Symptomology, Functional Impact, And Treatment Of People With Neurofibromatosis Type 1, Frank D Buono, Lauretta E Grau, Matthew E Sprong, Kenneth L Morford, Kimberly J Johnson, David H Gutmann

Open Access Publications

Introduction: Neurofibromatosis type 1 (NF1) is a neurogenetic disorder affecting 1 in 3000 people worldwide, where individuals are prone to develop benign and malignant tumors. In addition, many people with NF1 complain of pain that limits their daily functioning. Due to the complexity of the disorder, there are few options for treating pain symptoms besides surgery and medications. Moreover, the spectrum of pain symptomatology and treatment, as well as the mechanisms underlying NF1-associated pain, has been understudied.

Methodology: To address this knowledge gap, we conducted a survey of 255 adults with NF1, leveraging the Washington University NF1 Patient Registry Initiative …

Long-Term Prospective Clinical And Radiographic Outcomes After Minimally Invasive Lateral Transiliac Sacroiliac Joint Fusion Using Triangular Titanium Implants, Peter G Whang, Emily Darr, S Craig Meyer, Don Kovalsky, Clay Frank, Harry Lockstadt, Robert Limoni, Andy J Redmond, Philip Ploska, Michael Oh, Abhineet Chowdhary, Daniel Cher, Travis Hillen

Open Access Publications

Background: Accumulating evidence supports the long-term safety and effectiveness of minimally invasive sacroiliac joint fusion (SIJF) for sacroiliac joint dysfunction.

Objective: To report 5-year clinical and radiographic follow-up in patients undergoing SIJF using triangular titanium implants (TTI).

Methods: One hundred and three subjects at 12 centers treated with SIJF using TTI in two prospective clinical trials (NCT01640353 and NCT01681004) were enrolled and followed in the current study (NCT02270203) with clinic visits at 3, 4 and 5 years. CT scans performed at 5 years were compared to prior CT scans (at 1 or 2 years) by an independent radiologist.

Results: Compared …

External Dacryocystorhinostomy: A Comparison Of Ultrasonic Bone Aspiration To High-Speed Drilling, Vikram A Shankar, Krishna Kalyam, Steven M Couch

Open Access Publications

Purpose: Piezosurgical tools utilize high-frequency ultrasonic oscillations to selectively cut mineralized bone and minimize damage to soft tissue and mucosa. The purpose of this study was to directly compare outcomes in external dacryocystorhinostomy (DCR) using a piezoelectric ultrasonic bone aspirator (UBA) versus a high-speed electric drill with a diamond burr.

Methods: A retrospective chart review was conducted on 145 consecutive patients who underwent external DCR by a single oculoplastic surgeon between 2012 and 2017. Collected data included baseline patient characteristics, presenting symptoms, operative details and complications, and postoperative symptoms.

Results: One hundred and seventy-three primary external DCRs performed on 145 …

Retinoic Acid Receptors In Acute Myeloid Leukemia Therapy, Orsola Di Martino, John S Welch

Open Access Publications

Retinoic acid (RA) signaling pathways regulate fundamental biological processes, such as cell proliferation, development, differentiation, and apoptosis. Retinoid receptors (RARs and RXRs) are ligand-dependent transcription factors. All-trans retinoic acid (ATRA) is the principal endogenous ligand for the retinoic acid receptor alpha (RARA) and is produced by the enzymatic oxidation of dietary vitamin A, whose deficiency is associated with several pathological conditions. Differentiation therapy using ATRA revolutionized the outcome of acute promyelocytic leukemia (APL), although attempts to replicate these results in other cancer types have been met with more modest results. A better knowledge of RA signaling in different leukemia contexts …

Genomic Characterization Of Antibiotic Resistant Escherichia Coli Isolated From Domestic Chickens In Pakistan, Muhammad Rafique, Robert F Potter, Aura Ferreiro, Meghan A Wallace, Abdul Rahim, Akbar Ali Malik, Naila Siddique, Muhammad Athar Abbas, Alaric W D'Souza, Carey-Ann D Burnham, Naeem Ali, Gautam Dantas

Open Access Publications

Poultry husbandry is important for the economic health of Pakistan, but the Pakistani poultry industry is negatively impacted by infections from

Membrane Potential Determined By Flow Cytometry Predicts Fertilizing Ability Of Human Sperm, Lis C Puga Molina, Stephanie Gunderson, Joan Riley, Pascal Lybaert, Aluet Borrego-Alvarez, Emily S Jungheim, Celia M Santi

Open Access Publications

Infertility affects 10 to 15% of couples worldwide, with a male factor contributing up to 50% of these cases. The primary tool for diagnosing male infertility is traditional semen analysis, which reveals sperm concentration, morphology, and motility. However, 25% of infertile men are diagnosed as normozoospermic, meaning that, in many cases, normal-appearing sperm fail to fertilize an egg. Thus, new information regarding the mechanisms by which sperm acquire fertilizing ability is needed to develop a clinically feasible test that can predict sperm function failure. An important feature of sperm fertilization capability in many species is plasma membrane hyperpolarization (membrane potential …

Implementation And Sustainability Of A Pharmacy-Led, Hospital-Wide Bedside Medication Delivery Program: A Qualitative Process Evaluation Using Re-Aim, Beth Prusaczyk, Amanda S Mixon, Sunil Kripalani

Open Access Publications

No abstract provided.

The Interplay Between Tissue Niche And Macrophage Cellular Metabolism In Obesity, Sabine Daemen, Joel D Schilling

Open Access Publications

Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct …

The Interplay Between Viral-Derived Mirnas And Host Immunity During Infection, Richa Mishra, Ashish Kumar, Harshad Ingle, Himanshu Kumar

Open Access Publications

MicroRNAs are short non-coding RNAs that play a crucial role in the regulation of gene expression during cellular processes. The host-encoded miRNAs are known to modulate the antiviral defense during viral infection. In the last decade, multiple DNA and RNA viruses have been shown to produce miRNAs known as viral miRNAs (v-miRNAs) so as to evade the host immune response. In this review, we highlight the origin and biogenesis of viral miRNAs during the viral lifecycle. We also explore the role of viral miRNAs in immune evasion and hence in maintaining chronic infection and disease. Finally, we offer insights into …

Ferroptotic Cell Death And Tlr4/Trif Signaling Initiate Neutrophil Recruitment After Heart Transplantation, Wenjun Li, Guoshuai Feng, Jason M Gauthier, Inessa Lokshina, Ryuji Higashikubo, Sarah Evans, Xinping Liu, Adil Hassan, Satona Tanaka, Markus Cicka, Hsi-Min Hsiao, Daniel Ruiz-Perez, Andrea Bredemeyer, Richard W Gross, Douglas L Mann, Yulia Y Tyurina, Andrew E Gelman, Valerian E Kagan, Andreas Linkermann, Kory J Lavine, Daniel Kreisel

Open Access Publications

Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation. Inhibition of necroptosis had no effect on neutrophil trafficking in cardiac grafts. We extend these observations to a model of coronary artery ligation-induced myocardial ischemia reperfusion injury where inhibition of ferroptosis resulted in …

Rrx-001 Followed By Platinum Plus Etoposide In Patients With Previously Treated Small-Cell Lung Cancer, Daniel Morgensztern, Michal Rose, Saiama N Waqar, John Morris, Patrick C Ma, Thomas Reid, Christina E Brzezniak, Karen G Zeman, Arvinda Padmanabhan, Joann Hirth, Alexander I Spira, Jane B Trepel, Sukhmani K Padda

Open Access Publications

BACKGROUND: This exploratory single-arm phase II study evaluated the efficacy and safety of RRx-001 followed by reintroduction of platinum plus etoposide in patients with previously treated small-cell lung cancer (SCLC).

METHODS: Patients were treated with RRx-001 4 mg IV on day 1 of each week of a 21-day cycle followed at progression by re-challenge with etoposide 80-100 IV mg/m

RESULTS: Twenty-six patients were enroled and received at least one dose of RRx-001. The median number of prior lines of therapy was 2 (range 1-9) and 19 (73.1%) patients had platinum-resistant disease. In the intention-to-treat population, one patient (3.8%) had complete …

Visualization Of Positive And Negative Sense Viral Rna For Probing The Mechanism Of Direct-Acting Antivirals Against Hepatitis C Virus, Dandan Liu, Philip R Tedbury, Shuiyun Lan, Andrew D Huber, Maritza N Puray-Chavez, Juan Ji, Eleftherios Michailidis, Mohsan Saeed, Tanyaradzwa P Ndongwe, Leda C Bassit, Raymond F Schinazi, Robert Ralston, Charles M Rice, Stefan G Sarafianos

Open Access Publications

RNA viruses are highly successful pathogens and are the causative agents for many important diseases. To fully understand the replication of these viruses it is necessary to address the roles of both positive-strand RNA ((+)RNA) and negative-strand RNA ((-)RNA), and their interplay with viral and host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) to stain both the abundant (+)RNA and the far less abundant (-)RNA in both hepatitis C virus (HCV)- and Zika virus-infected cells, and combined these analyses with visualization of viral proteins through confocal imaging. We were able to phenotypically examine HCV-infected cells …

Mobilized Peripheral Blood: An Updated Perspective, Darja Karpova, Michael P Rettig, John F Dipersio

Open Access Publications

Enforced egress of hematopoietic stem cells (HSCs) out of the bone marrow (BM) into the peripheral circulation, termed mobilization, has come a long way since its discovery over four decades ago. Mobilization research continues to be driven by the need to optimize the regimen currently available in the clinic with regard to pharmacokinetic and pharmacodynamic profile, costs, and donor convenience. In this review, we describe the most recent findings in the field and how we anticipate them to affect the development of mobilization strategies in the future. Furthermore, the significance of mobilization beyond HSC collection, i.e. for chemosensitization, conditioning, and …

Tp53 Mutation Status Divides Myelodysplastic Syndromes With Complex Karyotypes Into Distinct Prognostic Subgroups, Detlef Haase, Matthew J. Walter, Et Al.

Open Access Publications

No abstract provided.

Clinical Events After Deferral Of Lad Revascularization Following Physiological Coronary Assessment, Sayan Sen, Jasvindar Singh, Et Al

Open Access Publications

No abstract provided.

Interpreting Neurologic Outcomes In A Changing Trial Design Landscape: An Analysis Of Heartware Left Ventricular Assist Device Using A Hybrid Intention To Treat Population, Claudius Mahr, Duc Thinh Pham, Nahush A. Mokadam, Scott C. Silvestry, Jennifer Cowger, Michael S. Kiernan, David A. D'Alessandro, Erin E. Coglianese, Muhammad Faraz Masood, Robert L. Kormos, Mary V. Jacoski, Jeffrey J. Teuteberg

Open Access Publications

No abstract provided.

Efficacy And Safety Of Eluxadoline In Patients With Irritable Bowel Syndrome With Diarrhea Who Report Inadequate Symptom Control With Loperamide: Relief Phase 4 Study, Darren M. Brenner, Gregory S. Sayuk, Catherine R. Gutman, Esther Jo, Steven J. R. Elmes, Louis W. C. Liu, Brooks D. Cash

Open Access Publications

No abstract provided.

Association Between Early Anatomic Response To Anti-Vascular Endothelial Growth Factor Therapy And Long-Term Outcome In Diabetic Macular Edema: An Independent Analysis Of Protocol I Study Data, Pravin U. Dugel, Joanna H. Campbell, Szilárd Kiss, Anat Loewenstein, Vanessa Shih, Xiaoshu Xu, Nancy Holekamp, Albert J. Augustin, Allen C. Ho, Victor H. Gonzalez, Scott M. Whitcup

Open Access Publications

No abstract provided.

Determining Population Stratification And Subgroup Effects In Association Studies Of Rare Genetic Variants For Nicotine Dependence, Ai-Ru Hsieh, Li-Shiun Chen, Ying-Ju Li, Cathy S. J. Fann

Open Access Publications

No abstract provided.