Digital Commons Network^™

Cancer In Youth Living With Hiv (Ylwhiv): A Narrative Review Of The Access To Oncological Services Among Ylwhiv And The Role Of Economic Strengthening In Child Health, Ruth G N Katumba, Ozge Sensoy Bahar, Kimberly J Johnson, Fred M Ssewamala

Open Access Publications

Youth Living with HIV/AIDS (YLWHIV) have a higher risk of developing immunodeficiency related illnesses including certain cancers than their general population counterparts of the same age. This narrative review of current available literature describes factors associated with pediatric access to oncological services, and the role economic strengthening could play in improving health outcomes for this vulnerable population. Findings suggest that both HIV-infected and -uninfected children living in low and middle-income countries struggle with access and adherence to cancer treatment and care. Cost of treatment is a major barrier to access and adherence. Asset-building savings programs may increase financial security and …

Chimerism In The Realm Of Hematopoietic Stem Cell Transplantation For Non-Malignant Disorders-A Perspective, Clare Zimmerman, Shalini Shenoy

Open Access Publications

Hematopoietic stem cell transplantation (HCT) is a curative intervention in non-malignant disorders (NMD) that benefit from donor-derived hematopoiesis, immunity, and establishment of vital cells or enzyme systems. Stability or reversal of disease symptoms depends on adequacy and long-term stability of donor cell engraftment in the compartment of interest. Unlike hematologic malignancies where complete replacement with donor derived hematopoiesis is desirable for a cure, NMD manifestations can often be controlled in the presence of mixed chimerism. This allows for exploration of reduced intensity conditioning regimens that can limit organ toxicity, late effects, and increase tolerability especially in young recipients or those …

Krabbe Disease Successfully Treated Via Monotherapy Of Intrathecal Gene Therapy, Allison M Bradbury, Xuntian Jiang, Mark S Sands, Daniel S Ory, Et Al

Open Access Publications

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased …

The Baby Bridge Program: A Sustainable Program That Can Improve Therapy Service Delivery For Preterm Infants Following Nicu Discharge, Roberta Pineda, Elizabeth Heiny, Patricia Nellis, Joan Smith, Jaqueline M. Mcgrath, Margaux Collins, Abigail Barker

Open Access Publications

OBJECTIVE: The aim of this project was to determine revenues and costs over time to assess the sustainability of the Baby Bridge program.

METHODS: The Baby Bridge program was developed to promote timely, consistent and high quality early therapy services for high-risk infants following neonatal intensive care unit (NICU) discharge. Key features of the Baby Bridge program were defined as: 1) having the therapist establish rapport with the family while in the NICU, 2) scheduling the first home visit within one week of discharge and continuing weekly visits until other services commence, 3) conducting comprehensive assessments to inform targeted interventions …

Focused Ultrasound For Safe And Effective Release Of Brain Tumor Biomarkers Into The Peripheral Circulation, Lifei Zhu, Arash Nazeri, Christopher Pham Pacia, Yimei Yue, Hong Chen

Open Access Publications

The development of noninvasive approaches for brain tumor diagnosis and monitoring continues to be a major medical challenge. Although blood-based liquid biopsy has received considerable attention in various cancers, limited progress has been made for brain tumors, at least partly due to the hindrance of tumor biomarker release into the peripheral circulation by the blood-brain barrier. Focused ultrasound (FUS) combined with microbubbles induced BBB disruption has been established as a promising technique for noninvasive and localized brain drug delivery. Building on this established technique, we propose to develop FUS-enabled liquid biopsy technique (FUS-LBx) to enhance the release of brain tumor …

Obesity Is A Risk Factor For Acute Promyelocytic Leukemia: Evidence From Population And Cross-Sectional Studies And Correlation With Flt3 Mutations And Polyunsaturated Fatty Acid Metabolism, Luca Mazzarella, Timothy J. Ley, Et Al.

Open Access Publications

No abstract provided.

Sv‑Hotspot: Detection And Visualization Of Hotspots Targeted By Structural Variants Associated With Gene Expression, Abdallah M. Eteleeb, David A. Quigley, Shuang G. Zhao, Duy Pham, Rendong Yang, Scott M. Dehm, Jingqin Luo, Felix Y. Feng, Ha X. Dang, Christopher A. Maher

Open Access Publications

No abstract provided.

Spatial Mapping Of The Collagen Distribution In Human And Mouse Tissues By Force Volume Atomic Force Microscopy, Annalisa Calò, Yevgeniy Romin, Rami Srouji, Constantinos P. Zambirinis, Ning Fan, Anthony Santella, Elvin Feng, Sho Fujisawa, Mesruh Turkekul, Sharon Huang, Amber L. Simpson, Michael D'Angelica, William R. Jarnagin, Katia Manova-Todorova

Open Access Publications

No abstract provided.

Impact Of Intraoperative Ocular Lubricants On Corneal Debridement Rate During Vitreoretinal Surgery, Michael L Mathison, Albert S Li, Yicheng K Bao, Andrew Jw Huang, Rithwick Rajagopal

Open Access Publications

Purpose: To compare surgical parameters among patients receiving Viscoat (sodium chondroitin sulfate 4%-sodium hyaluronate 3%) or Goniosol (hydroxypropyl methylcellulose 2.5%) as topical lubricants for retinal surgery.

Methods: This was a retrospective analysis of patients undergoing retinal surgery between March 2013 and March 2018 using Goniosol or Viscoat as adjuvants. Primary outcome measures were rate of corneal debridement and operative time between groups, compared using

Results: Compared to Viscoat (n=319), the Goniosol group (n=210) had more frequent intraoperative corneal debridement (21.4% vs 0,

Conclusion: These findings suggest potential advantages of using Viscoat over Goniosol for corneal lubrication to aid visualization during …

Germline Sequencing Identifies Rare Variants In Finnish Subjects With Familial Germ Cell Tumors, Erin L Crowgey, Tea Soini, Nidhi Shah, Satu-Liisa Pauniaho, Pekka Lahdenne, David B Wilson, Markku Heikinheimo, Todd E Druley

Open Access Publications

Purpose: Pediatric germ cell tumors are rare, representing about 3% of childhood malignancies in children less than 15 years of age, presenting in neonates or adolescents with a greater incidence noted in older adolescents. Aberrations in primordial germ cell proliferation/differentiation can lead to a variety of neoplasms, including teratomas, embryonal carcinoma, choriocarcinoma, and yolk sac tumors.

Patients and Methods: Three Finnish families with varying familial germ cell tumors were identified, and whole-genome sequencing was performed using an Illumina sequencing platform. In total, 22 unique subjects across the three families were sequenced. Family 1 proband (female) was affected by malignant ovarian …

Radically Open Dialectical Behavior Therapy: Social Signaling, Transdiagnostic Utility And Current Evidence, Kirsten Gilbert, Karyn Hall, R Trent Codd

Open Access Publications

At the core of an overcontrolled personality and coping style is a tendency to have too much self-control, exhibiting as behavioral and cognitive inflexibility, high inhibition of emotion, high detail-focused processing and perfectionism, and a lack of social connectedness. Overcontrol underlies a wide variety of psychiatric illnesses and as such, an innovative transdiagnostic therapy called Radically Open Dialectical Behavior Therapy (RO DBT) has been developed to treat disorders characterized by overcontrol. RO DBT targets maladaptive social signaling in order to help individuals "rejoin the tribe," hypothesizing that increasing social connectedness by means of targeting social signaling is the central mechanism …

Updated Perspectives On The Management Of Multiple Myeloma In Older Patients: Focus On Lenalidomide, Kelly L Schoenbeck, Tanya M Wildes

Open Access Publications

Multiple myeloma is a hematologic malignancy that predominantly affects older adults, with a median age at diagnosis of 70 years old. A mainstay of multiple myeloma treatment is lenalidomide, which is an immunomodulatory drug (IMiD) that changed the treatment paradigm for multiple myeloma. This is particularly true for older adults who do not undergo autologous stem cell transplantation (ASCT). Several pivotal trials summarized in this review demonstrate the efficacy and safety of lenalidomide in older adults with multiple myeloma, including significant improvements in response rates, progression-free survival and overall survival in the first-line and relapsed/refractory settings. Potential adverse effects include …

Impact Of Preoperative Chlorhexidine Gluconate (Chg) Application Methods On Preoperative Chg Skin Concentration, Bobby G Warren, Alicia Nelson, David K Warren, Meghan A Baker, Candace Miller, Tracey Habrock, Jahnavi Bongu, Abinav Gowda, Jacob Johnson, Deverick J Anderson, Cdc Prevention Epicenters Program

Open Access Publications

Elective surgical patients routinely bathe with chlorhexidine gluconate (CHG) at home days prior to their procedures. However, the impact of home CHG bathing on surgical site CHG concentration is unclear. We examined 3 different methods of applying CHG and hypothesized that different application methods would impact resulting CHG skin concentration.

Deeph&M: Estimating Single-Cpg Hydroxymethylation And Methylation Levels From Enrichment And Restriction Enzyme Sequencing Methods, Yu He, Hyo Sik Jang, Xiaoyun Xing, Daofeng Li, Michael J Vasek, Joseph D Dougherty, Ting Wang

Open Access Publications

Increased appreciation of 5-hydroxymethylcytosine (5hmC) as a stable epigenetic mark, which defines cell identity and disease progress, has engendered a need for cost-effective, but high-resolution, 5hmC mapping technology. Current enrichment-based technologies provide cheap but low-resolution and relative enrichment of 5hmC levels, while single-base resolution methods can be prohibitively expensive to scale up to large experiments. To address this problem, we developed a deep learning-based method, "DeepH&M," which integrates enrichment and restriction enzyme sequencing methods to simultaneously estimate absolute hydroxymethylation and methylation levels at single-CpG resolution. Using 7-week-old mouse cerebellum data for training the DeepH&M model, we demonstrated that the 5hmC …

High-Throughput Single-Cell Functional Elucidation Of Neurodevelopmental Disease-Associated Genes Reveals Convergent Mechanisms Altering Neuronal Differentiation, Matthew A Lalli, Denis Avey, Joseph D Dougherty, Jeffrey Milbrandt, Robi D Mitra

Open Access Publications

The overwhelming success of exome- and genome-wide association studies in discovering thousands of disease-associated genes necessitates developing novel high-throughput functional genomics approaches to elucidate the molecular mechanisms of these genes. Here, we have coupled multiplexed repression of neurodevelopmental disease-associated genes to single-cell transcriptional profiling in differentiating human neurons to rapidly assay the functions of multiple genes in a disease-relevant context, assess potentially convergent mechanisms, and prioritize genes for specific functional assays. For a set of 13 autism spectrum disorder (ASD)-associated genes, we show that this approach generated important mechanistic insights, revealing two functionally convergent modules of ASD genes: one that …

Affording Autism An Early Brain Development Re-Definition, Ami Klin, Megan Micheletti, Cheryl Klaiman, Sarah Shultz, John N Constantino, Warren Jones

Open Access Publications

The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD …

Immune Reconstitution In Pediatric Patients Following Hematopoietic Cell Transplant For Non-Malignant Disorders, Sima T Bhatt, Jeffrey J Bednarski

Open Access Publications

Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow failure syndromes, and primary immunodeficiencies. Early establishment of donor-derived innate and adaptive immunity following HCT is associated with improved overall survival, lower risk of infections and decreased incidence of graft failure. Immune reconstitution (IR) is impacted by numerous clinical variables including primary disease, donor characteristics, conditioning regimen, and graft versus host disease (GVHD). Recent advancements in HCT have been directed at reducing toxicity of conditioning therapy, expanding donor availability through use of alternative donor sources, and addressing morbidity from GVHD with novel …

Targeting Cxcr4 In Aml And All, Daniel Cancilla, Michael P Rettig, John F Dipersio

Open Access Publications

The interaction of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts with the bone marrow microenvironment regulates self-renewal, growth signaling, as well as chemotherapy resistance. The chemokine receptor, CXC receptor 4 (CXCR4), with its ligand chemokine ligand 12 (CXCL12), plays a key role in the survival and migration of normal and malignant stem cells to the bone marrow. High expression of CXCR4 on AML and ALL blasts has been shown to be a predictor of poor prognosis for these diseases. Several small molecule inhibitors, short peptides, antibodies, and antibody drug conjugates have been developed for the purposes of …

Risk Factors For Incident Dementia Among Older Cubans, Geeske Peeters, Arianna Almirall Sanchez, Jorge Llibre Guerra, Brian Lawlor, Rose Anne Kenny, Kristine Yaffe, Juan Llibre Rodriguez

Open Access Publications

No abstract provided.

The Pathway To Secondary Prevention Of Alzheimer's Disease, Eric Mcdade, Martin M Bednar, H Robert Brashear, David S Miller, Paul Maruff, Christopher Randolph, Zahinoor Ismail, Maria C Carrillo, Christopher J Weber, Lisa J Bain, Ann Marie Hake

Open Access Publications

Alzheimer's disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer's Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW.

Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten

Open Access Publications

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of …

Tamoxifen Acts As A Parietal Cell Protonophore, E H Manning, L A Lapierre, J C Mills, J R Goldenring

Open Access Publications

No abstract provided.

Genome-Scale Analysis Identifies Novel Transcript-Variants In Esophageal Adenocarcinoma, B P D Purkayastha, E R Chan, D Ravillah, L Ravi, R Gupta, M I Canto, J S Wang, N J Shaheen, J E Willis, A Chak, V Varadan, K Guda

Open Access Publications

No abstract provided.

Reaching Consensus On Principles Of Stakeholder Engagement In Research, Melody S. Goodman, Nicole Ackermann, Deborah J. Bowen, Members Of The Delphi Panel, Vetta Sanders Thompson

Open Access Publications

No abstract provided.

Building Access To Care In Adult Sickle Cell Disease: Defining Models Of Care, Essential Components, And Economic Aspects, Julie Kanter, Allison King, Et Al.

Open Access Publications

No abstract provided.

Pemphigus Foliaceus In A Patient With Gastrointestinal Stromal Tumor Treated With Adjuvant Imatinib Mesylate, Hal A. Lewis, David Y. Chen, Ilana S. Rosman, Joel Picus, Milan J. Anadkat

Open Access Publications

No abstract provided.

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G. Pestell, Yunguang Sun, Jun Zhao, Mathew C. Casimiro, Zhiping Li, Michael P. Lisanti, Peter A. Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G. Pestell

Open Access Publications

No abstract provided.

Multitasking By The Oc Lineage During Bone Infection: Bone Resorption, Immune Modulation, And Microbial Niche, Philip M Roper, Christine Shao, Deborah J Veis

Open Access Publications

Bone infections, also known as infectious osteomyelitis, are accompanied by significant inflammation, osteolysis, and necrosis. Osteoclasts (OCs) are the bone-resorbing cells that work in concert with osteoblasts and osteocytes to properly maintain skeletal health and are well known to respond to inflammation by increasing their resorptive activity. OCs have typically been viewed merely as effectors of pathologic bone resorption, but recent evidence suggests they may play an active role in the progression of infections through direct effects on pathogens and via the immune system. This review discusses the host- and pathogen-derived factors involved in the in generation of OCs during …

Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis In The Degenerative Disc Microenvironment Through Activation Of The Hif-1a/Yap Signaling Pathway, Zhe Wang, Min Cui, Yanji Qu, Ruijun He, Wei Wu, Hui Lin, Zengwu Shao

Open Access Publications

No abstract provided.

Regulation Of Signaling And Metabolism By Lipin-Mediated Phosphatidic Acid Phosphohydrolase Activity, Andrew J Lutkewitte, Brian N Finck

Open Access Publications

Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound …