Digital Commons Network^™

Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne

Open Access Publications

The resurgent component of the voltage-gated sodium current (I

Tumor Lysis Syndrome In A Patient With Metastatic Endometrial Cancer Treated With Lattice Stereotactic Body Radiation Therapy, Joshua P Schiff, Matthew B Spraker, Sai Duriseti, Sana Shaikh, Haris F Murad, David G Mutch, Clifford G Robinson, James Kavanaugh, Alexander J Lin

Open Access Publications

No abstract provided.

A Test Of The Pioneer Factor Hypothesis Using Ectopic Liver Gene Activation, Jeffrey L. Hansen, Kaiser J. Loell, Barak A. Cohen

Open Access Publications

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and …

A Content Analysis Of 100 Qualitative Health Research Articles To Examine Researcher-Participant Relationships And Implications For Data Sharing, Jessica Mozersky, Annie Friedrich, James Dubois

Open Access Publications

No abstract provided.

An Overview Of Treatment Options For Patients With Relapsed/Refractory Multiple Myeloma And Renal Impairment, Meletios A Dimopoulos, Joseph Mikhael, Evangelos Terpos, Xavier Leleu, Philippe Moreau, Joan Bladé, Jin Seok Kim, Keith Stockerl-Goldstein, Paul G Richardson

Open Access Publications

Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. …

Quantifying Rural Disparity In Healthcare Utilization In The United States: Analysis Of A Large Midwestern Healthcare System, Akua Nuako, Jingxia Liu, Giang Pham, Nina Smock, Aimee James, Timothy Baker, Laura Bierut, Graham Colditz, Li-Shiun Chen

Open Access Publications

PURPOSE: The objective of this study is to identify how predisposing characteristics, enabling factors, and health needs are jointly and individually associated with epidemiological patterns of outpatient healthcare utilization for patients who already interact and engage with a large healthcare system.

METHODS: We retrospectively analyzed electronic medical record data from 1,423,166 outpatient clinic visits from 474,674 patients in a large healthcare system from June 2018-March 2019. We evaluated patients who exclusively visited rural clinics versus patients who exclusively visited urban clinics using Chi-square tests and the generalized estimating equation Poisson regression methodology. The outcome was healthcare use defined by the …

Impact Of Motile Ciliopathies On Human Development And Clinical Consequences In The Newborn, Rachael Hyland, Steven L. Brody

Open Access Publications

No abstract provided.

Deep Learning Supplants Visual Analysis By Experienced Operators For The Diagnosis Of Cardiac Amyloidosis By Cine-Cmr, Philippe Germain, Armine Vardazaryan, Nicolas Padoy, Aissam Labani, Catherine Roy, Thomas Hellmut Schindler, Soraya El Ghannudi

Open Access Publications

BACKGROUND: Diagnosing cardiac amyloidosis (CA) from cine-CMR (cardiac magnetic resonance) alone is not reliable. In this study, we tested if a convolutional neural network (CNN) could outperform the visual diagnosis of experienced operators.

METHOD: 119 patients with cardiac amyloidosis and 122 patients with left ventricular hypertrophy (LVH) of other origins were retrospectively selected. Diastolic and systolic cine-CMR images were preprocessed and labeled. A dual-input visual geometry group (VGG ) model was used for binary image classification. All images belonging to the same patient were distributed in the same set. Accuracy and area under the curve (AUC) were calculated per frame …

Cerebral Perfusion And Sensory Testing Results Differ In Interstitial Cystitis/Bladder Pain Syndrome Patients With And Without Fibromyalgia: A Site-Specific Mapp Network Study, Georg Deutsch, Hrishikesh Deshpande, H Henry Lai, Jason J Kutch, Timothy J Ness

Open Access Publications

Purpose: Fibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity.

Patients and Methods: Female subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis …

Tricuspid Valve Intervention At The Time Of Pulmonary Valve Replacement In Adults With Congenital Heart Disease: A Systematic Review And Meta-Analysis, Jef Van Den Eynde, Connor P Callahan, Mauro Lo Rito, Nabil Hussein, Horacio Carvajal, Alvise Guariento, Arjang Ruhparwar, Alexander Weymann, Werner Budts, Marc Gewillig, Michel Pompeu Sá, Shelby Kutty

Open Access Publications

Background Tricuspid regurgitation (TR) is a common finding in adults with congenital heart disease referred for pulmonary valve replacement (PVR). However, indications for combined valve surgery remain controversial. This study aimed to evaluate early results of concomitant tricuspid valve intervention (TVI) at the time of PVR. Methods and Results Observational studies comparing TVI+PVR and isolated PVR were identified by a systematic search of published research. Random-effects meta-analysis was performed, comparing outcomes between the 2 groups. Six studies involving 749 patients (TVI+PVR, 278 patients; PVR, 471 patients) met the eligibility criteria. In the pooled analysis, both TVI+PVR and PVR reduced TR …

Impact Of Semi-Annual Albendazole On Lymphatic Filariasis And Soil-Transmitted Helminth Infection: Parasitological Assessment After 14 Rounds Of Community Treatment, Sébastien D S Pion, Cédric B Chesnais, Gary J Weil, Frédéric Louya, Michel Boussinesq, François Missamou

Open Access Publications

Between October 2012 and October 2015, we conducted a community trial to assess the impact of semi-annual (twice yearly) community treatment with albendazole on lymphatic filariasis in Seke Pembe, a village in the Republic of the Congo. Semi-annual community treatment with albendazole has been continued in the community since October 2015. We conducted an additional parasitological assessment survey in October 2019, 6 months after the 14th round of semi-annual treatment. Between October 2012 and October 2015, Wuchereria bancrofti antigenemia and microfilaremia rates in the community had decreased from 17.3% to 4.7% and from 5.3% to 0.3%, respectively. In October 2019, …

The Relationship Between Acute And Chronic Pancreatitis With Pancreatic Adenocarcinoma: Review, Tamara Alhobayb, Rahul Peravali, Motaz Ashkar

Open Access Publications

No abstract provided.

Multicenter Randomized Phase Ii Trial Of Atezolizumab With Or Without Cobimetinib In Biliary Tract Cancers, Mark Yarchoan, Andrea Wang-Gillam, Et Al

Open Access Publications

BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS).RESULTSSeventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a …

Antibody-Drug Conjugates Plus Janus Kinase Inhibitors Enable Mhc-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation, Stephen P Persaud, Julie K Ritchey, Sena Kim, Sora Lim, Peter G Ruminski, Matthew L Cooper, Michael P Rettig, Jaebok Choi, John F Dipersio

Open Access Publications

Despite the curative potential of hematopoietic stem cell transplantation (HSCT), conditioning-associated toxicities preclude broader clinical application. Antibody-drug conjugates (ADCs) provide an attractive approach to HSCT conditioning that minimizes toxicity while retaining efficacy. Initial studies of ADC conditioning have largely focused on syngeneic HSCT. However, to treat acute leukemias or induce tolerance for solid organ transplantation, this approach must be expanded to allogeneic HSCT (allo-HSCT). Using murine allo-HSCT models, we show that pharmacologic Janus kinase 1/2 (JAK1/2) inhibition combined with CD45- or cKit-targeted ADCs enables robust multilineage alloengraftment. Strikingly, myeloid lineage donor chimerism exceeding 99% was achievable in fully MHC-mismatched HSCT …

Bleeding Assessment Tools In The Diagnosis Of Vwd In Adults And Children: A Systematic Review And Meta-Analysis Of Test Accuracy, Mohamad A. Kalot, Jorge Di Paola, Et Al

Open Access Publications

No abstract provided.

Activation Of The Α1Β2Γ2l Gaba Receptor By Physiological Agonists, Spencer R Pierce, Allison L Germann, Gustav Akk

Open Access Publications

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Axicabtagene Ciloleucel As Second-Line Therapy For Large B-Cell Lymphoma, Frederick L Locke, Armin Ghobadi, Et Al

Open Access Publications

BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.

METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was …

Hedgehog-Interacting Protein Is A Multimodal Antagonist Of Hedgehog Signalling, Samuel C Griffiths, Rebekka A Schwab, Kamel El Omari, Benjamin Bishop, Ellen J Iverson, Tomas Malinauskas, Ramin Dubey, Mingxing Qian, Douglas F Covey, Robert J C Gilbert, Rajat Rohatgi, Christian Siebold

Open Access Publications

Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the …

Regenerative Responses Of Rabbit Corneal Endothelial Cells To Stimulation By Fibroblast Growth Factor 1 (Fgf1) Derivatives, Tthx1001 And Tthx1114, Jessica Weant, David D Eveleth, Amuthakannan Subramaniam, Jennifer Jenkins-Eveleth, Michael Blaber, Ling Li, David M Ornitz, Asaf Alimardanov, Trevor Broadt, Hui Dong, Vinay Vyas, Xiaoyi Yang, Ralph A Bradshaw

Open Access Publications

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC

Asthma Reduces Glioma Formation By T Cell Decorin-Mediated Inhibition Of Microglia, Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley, Andrea K Goldstein, Elizabeth Cordell, Xia Ge, Joel R Garbow, Michael J Holtzman, David H Gutmann

Open Access Publications

To elucidate the mechanisms underlying the reduced incidence of brain tumors in children with Neurofibromatosis type 1 (NF1) and asthma, we leverage Nf1 optic pathway glioma (Nf1

High-Throughput Functional Analysis Of Cftr And Other Apically Localized Proteins In Ipsc-Derived Human Intestinal Organoids, Sunny Xia, Zoltán Bozóky, Michelle Di Paola, Onofrio Laselva, Saumel Ahmadi, Jia Xin Jiang, Amy L Pitstick, Chong Jiang, Daniela Rotin, Christopher N Mayhew, Nicola L Jones, Christine E Bear

Open Access Publications

Induced Pluripotent Stem Cells (iPSCs) can be differentiated into epithelial organoids that recapitulate the relevant context for CFTR and enable testing of therapies targeting Cystic Fibrosis (CF)-causing mutant proteins. However, to date, CF-iPSC-derived organoids have only been used to study pharmacological modulation of mutant CFTR channel activity and not the activity of other disease-relevant membrane protein constituents. In the current work, we describe a high-throughput, fluorescence-based assay of CFTR channel activity in iPSC-derived intestinal organoids and describe how this method can be adapted to study other apical membrane proteins. Specifically, we show how this assay can be employed to study …

Using Nasal Povidone-Iodine To Prevent Bloodstream Infections And Transmission Of Staphylococcus Aureus Among Haemodialysis Patients: A Stepped-Wedge Cluster Randomised Control Trial Protocol, Ana-Monica Racila, Amy O'Shea, Rajeshwari Nair, Kimberly Dukes, Loreen Herwaldt, Linda Boyken, Daniel Diekema, Melissa Ward, Jason Cobb, Jesse Jacob, David Pegues, Susan Bleasdale, Anitha Vijayan, Anubha Mutneja, Mony Fraer, Debra O'Connell-Moore, Pam Tolomeo, Minerva Mendez, Erin Jaworski, Marin Schweizer

Open Access Publications

INTRODUCTION: Approximately 38% of haemodialysis patients carry

METHODS AND ANALYSIS: We will perform an open-label, stepped-wedge cluster randomised trial to assess the effectiveness of nasal PVI compared with standard care. Sixteen outpatient haemodialysis units will participate in the study. The 3-year trial period will be divided into a 4-month baseline period and eight additional 4-month time blocks. The primary outcome of the study will be

ETHICS AND DISSEMINATION: This study has received IRB approval from all study sites. A Data Safety and Monitoring Board will monitor this multicentre clinical trial. We will present our results at international meetings. The study …

A Deep Learning Framework Identifies Dimensional Representations Of Alzheimer's Disease From Brain Structure, Zhijian Yang, Ilya M. Nasrallah, John C. Morris, Et Al

Open Access Publications

No abstract provided.

Minimizing The Impact Of The Triple Burden Of Covid-19, Tuberculosis And Hiv On Health Services In Sub-Saharan Africa, Jean B Nachega, Nathan Kapata, Nadia A Sam-Agudu, Eric H Decloedt, Patrick D M C Katoto, Tumaini Nagu, Peter Mwaba, Dorothy Yeboah-Manu, Pascalina Chanda-Kapata, Francine Ntoumi, Elvin H Geng, Alimuddin Zumla

Open Access Publications

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of …

Investigating Late-Onset Pompe Prevalence In Neuromuscular Medicine Academic Practices, Marie Wencel, Alan Pestronk, Julaine Florence, Et Al

Open Access Publications

No abstract provided.

Trajectory Of Emotion Dysregulation In Positive And Negative Affect Across Childhood Predicts Adolescent Emotion Dysregulation And Overall Functioning, Alecia C. Vogel, Rebecca Tillman, Nourhan M. El-Sayed, Joshua J. Jackson, Susan B. Perlman, Deanna M. Barch, Joan L. Luby

Open Access Publications

No abstract provided.

Prediction Of Chronic Postsurgical Pain In Adults: A Protocol For Multivariable Prediciton Model Development, Nicholas Papadomanolakis-Pakis, Simon Haroutounian, Christian Christiansen, Lone Nikolajsen

Open Access Publications

No abstract provided.

Long-Term Outcomes Of Primary Cardiac Malignant Tumors: Difference Between African American And Caucasian Population, Quoc Bui, Tam N M Ngo, Jan Mazur, Vy Pham, Cassady Palmer, Binh Q Truong, Eugene S Chung, Huy G Vuong, Vien T Truong

Open Access Publications

BACKGROUND: The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long-term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations.

METHODS: The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety-four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log-rank test was used to compare the difference in mortality between two populations and presented by …

Neutrophil Extracellular Trap Inhibition Increases Inflammation, Bacteraemia And Mortality In Murine Necrotizing Enterocolitis, Hala Chaaban, Kathryn Burge, Jeffrey Eckert, Ravi S Keshari, Robert Silasi, Cristina Lupu, Barbara Warner, Marilyn Escobedo, Michael Caplan, Florea Lupu

Open Access Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease affecting primarily premature infants. The disease is characterized by intestinal inflammation and leucocyte infiltration, often progressing to necrosis, perforation, systemic inflammatory response and death. Neutrophil extracellular traps (NETs), denoting nuclear DNA, histone and antimicrobial protein release, have been suggested to play a role in NEC. This study aimed to determine the role of NETs in NEC and explore the effect of chloramidine, a NET inhibitor, on a murine NEC-like intestinal injury model. Blood and intestinal tissues were collected from infants diagnosed with ≥ Stage II NEC, and levels of nucleosomes and NETs, …

From Canines To Humans: Clinical Importance Of Staphylococcus Pseudintermedius, Karen C. Carroll, Carey-Ann D. Burnham, Lars F. Westblade

Open Access Publications

No abstract provided.