Medical Specialties Commons^™

Longitudinal Survival Outcomes In Allogeneic Stem Cell Transplantation: An Institutional Experience., Justin Jiang, Audrey M Sigmund, Qiuhong Zhao, Patrick Elder, Don M Benson, Sumithira Vasu, Samantha Jaglowski, Alice Mims, Hannah Choe, Karilyn Larkin, Jonathan E Brammer, Sarah Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Yvonne A Efebera, Nidhi Sharma

Oncology Articles

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological disorders, but is often complicated by relapse of the underlying disease, graft-versus-host disease (GVHD), and infectious complications. We conducted a retrospective analysis on patients undergoing allo-SCT from 1984 to 2018 to better understand how survival has changed longitudinally with therapeutic advancements made to mitigate these complications. Method: We analyzed data from 1943 consecutive patients who received allo-SCT. Patients were divided into groups (gps) based on the year (yr) of transplant. Primary endpoints were overall survival (OS), progression free survival (PFS), and GVHD-free relapse-free survival (GRFS). Secondary …

Tumor-Intrinsic Sirpa Promotes Sensitivity To Checkpoint Inhibition Immunotherapy In Melanoma, Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V Kumar, Rehan Akbani, Yiling Lu, Han Liang

Faculty, Staff and Student Publications

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8+ T cells in a co-culture …

Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased Fgf19 Secretion In Neonatal Pigs, Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Valeria Melendez Hebib, Harry Dawson, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean vs vaginal birth on the development of bile acid and fibroblast growth factor 19 (FGF19) signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent cesarean delivery on …

Effectiveness Of Skill‑Building Interventions For Informal Caregivers Of Adults With Cancer: A Systematic Review, M. Courtney Hughes, Sadia Afrin, Tamara Hamlish

Faculty Articles, Papers, and Other Scholarship

Over 19 million people worldwide were diagnosed with cancer in 2020. Informal caregivers of adults with cancer play an important role in helping their loved ones with cancer yet often receive little support in developing the necessary skills for caregiving. A systematic review of skill-building interventions for informal caregivers of adults with cancer was conducted across three electronic databases for academic articles published through February 2022. PRISMA reporting guidelines were followed throughout this review, the Mixed Methods Appraisal Tool was used to assess study quality, and results were summarized in a narrative synthesis. The main components of skill-building interventions examined …

Region-Specific Denoising Identifies Spatial Co-Expression Patterns And Intra-Tissue Heterogeneity In Spatially Resolved Transcriptomics Data, Linhua Wang, Mirjana Maletic-Savatic, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Spatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring …

Tumor Suppressor Dear1 Regulates Mammary Epithelial Cell Fate And Predicts Early Onset And Metastasis In Triple Negative Breast Cancer, Uyen Q Le, Nanyue Chen, Seetharaman Balasenthil, Eugene Lurie, Fei Yang, Suyu Liu, Laura Rubin, Luisa Maren Solis Soto, Maria Gabriela Raso, Harsh Batra, Aysegul A Sahin, Ignacio I Wistuba, Ann Mcneill Killary

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are …

Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean

Faculty, Staff and Student Publications

Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the …

Medicc2: Whole-Genome Doubling Aware Copy-Number Phylogenies For Cancer Evolution, Tom L Kaufmann, Marina Petkovic, Thomas B K Watkins, Emma C Colliver, Sofya Laskina, Nisha Thapa, Darlan C Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi, Roland F Schwarz

Faculty, Staff and Student Publications

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.

Effect Of Dexamethasone On Newborn Survival At Different Administration-To-Birth Intervals: A Secondary Analysis Of The Who Action (Antenatal Corticosteroids For Improving Outcomes In Preterm Newborn)-I Trial, Who Action Trials Collaborators, Olufemi T. Oladapo, Joshua P. Vogel, Gilda Piaggio, My Huong Nguyen, Fernando Althabe, Rajiv Bahl, Suman P. N. Rao, Shabina Ariff, Sajid Bashir Soofi, Lumaan Sheikh

Department of Paediatrics and Child Health

Background: The WHO ACTION-I trial demonstrated that dexamethasone significantly reduced neonatal mortality when administered to women at risk of early preterm birth in low-resource countries. We conducted a secondary analysis to determine how these benefits can be optimised, by evaluating the effect of dexamethasone compared to placebo on newborn mortality and severe respiratory distress outcomes at different administration-to-birth intervals, and identifying the interval with the greatest benefits.
Methods: The WHO ACTION-I trial was a multi-country, individually-randomised, parallel-group, double-blind, placebo-controlled trial. It was conducted in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Women with a viable singleton or multiple …

High Throughput Sequencing For Clinical Tuberculosis: An Overview, Tara E Ness, Andrew Dinardo, Maha R Farhat

Faculty, Staff and Students Publications

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field.

Conformational Motions And Ligand-Binding Underlying Gating And Regulation In Ip3r Channel, Guizhen Fan, Mariah R Baker, Lara E Terry, Vikas Arige, Muyuan Chen, Alexander B Seryshev, Matthew L Baker, Steven J Ludtke, David I Yule, Irina I Serysheva

Faculty, Staff and Students Publications

Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP3 and Ca2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP3R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP3 binding relies upon intrinsic flexibility of the ARM2 domain in the …

Applications Of Covalent Chemistry In Targeted Protein Degradation, Dong Lu, Xin Yu, Hanfeng Lin, Ran Cheng, Erika Y Monroy, Xiaoli Qi, Meng C Wang, Jin Wang

Faculty, Staff and Students Publications

Proteolysis-targeting chimeras (PROTACs) and targeted covalent inhibitors (TCIs) are currently two exciting strategies in the fields of chemical biology and drug discovery. Extensive research in these two fields has been conducted, and significant progress in these fields has resulted in many clinical candidates, some of which have been approved by FDA. Recently, a novel concept termed covalent PROTACs that combine these two strategies has emerged and gained an increasing interest in the past several years. Herein, we briefly review and highlight the mechanism and advantages of TCIs and PROTACs, respectively, and the recent development of covalent PROTACs using irreversible and …

Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan

Faculty Scholarship

Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases …

The Gain Of Function Scn1a Disorder Spectrum: Novel Epilepsy Phenotypes And Therapeutic Implications, Andreas Brunklaus, Tobias Brünger, Tony Feng, Carmen Fons, Anni Lehikoinen, Eleni Panagiotakaki, Mihaela Adela Vintan, Joseph Symonds, James Andrew, Alexis Arzimanoglou, Sarah Delima, Julie Gallois, Donncha Hanrahan, Gaetan Lesca, Stewart Macleod, Dragan Marjanovic, Amy Mctague, Noemi Nuñez-Enamorado, Eduardo Perez-Palma, M. Scott Perry, Karen Pysden, Sophie J. Russ-Hall, Ingrid E. Scheffer, Krystal Sully, Steffen Syrbe, Ulvi Vaher, Murugan Velayutham

School of Medicine Faculty Publications

Brain voltage-gated sodium channel NaV1.1 (SCN1A) loss-of-function variants cause the severe epilepsy Dravet syndrome, as well as milder phenotypes associated with genetic epilepsy with febrile seizures plus. Gain of function SCN1A variants are associated with familial hemiplegic migraine type 3. Novel SCN1A-related phenotypes have been described including early infantile developmental and epileptic encephalopathy with movement disorder, and more recently neonatal presentations with arthrogryposis. Here we describe the clinical, genetic and functional evaluation of affected individuals. Thirty-five patients were ascertained via an international collaborative network using a structured clinical questionnaire and from the literature. We performed whole-cell voltage-clamp electrophysiological recordings comparing …

Early And Progressive Mobility: A Program Implementation Strategy For High Acuity Patient Care Locations, Stefani Poland

Student Scholarly Projects

Despite an increase in the promotion of early progressive mobility, its decrease in hospital-acquired complications and improvement of patient outcomes, there remains a reluctance in staff commitment to daily evaluation and implementation. This is largely due to the fact nurses or other interprofessional staff are the primary individuals responsible for this change in process. A lack of confidence in staff to correctly identify patients that meet criteria and anxiety regarding the safe transfer or mobilization of patients, particularly in high acuity settings have been identified as major barriers. The PICOT question that guided this program development of a CBO toolkit …

Pancreaticoduodenectomy In 11-Year-Old Male With A Non-Functional Pancreatic Neuroendocrine Tumor, Whitney Elks, Jessa Rose Li, Alexander Zajack, Lance Horner, Alan Ikeda, Charles St Hill, Michael Scheidler, Shirong Chang

School of Medicine Faculty Research

Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms and are even more uncommon in the pediatric patients, thus leading to a lack of clinical research on diagnosis and management in this population. The purpose of this report is to review relevant literature and discuss a rare occurrence of a non-functioning pNET in a pediatric patient. This is a report of an 11-year-old male who presented with symptomatic anemia and was found to have a 6 cm mass near the pancreatic head with erosion into the duodenum. Surgical biopsy demonstrated a non-functioning pNET. He was successfully managed with complete surgical resection …

Ontology-Based Feature Engineering In Machine Learning Workflows For Heterogeneous Epilepsy Patient Records, Satya S Sahoo, Katja Kobow, Jianzhe Zhang, Jeffrey Buchhalter, Mojtaba Dayyani, Dipak P Upadhyaya, Katrina Prantzalos, Meenakshi Bhattacharjee, Ingmar Blumcke, Samuel Wiebe, Samden D Lhatoo

Faculty, Staff and Student Publications

Biomedical ontologies are widely used to harmonize heterogeneous data and integrate large volumes of clinical data from multiple sources. This study analyzed the utility of ontologies beyond their traditional roles, that is, in addressing a challenging and currently underserved field of feature engineering in machine learning workflows. Machine learning workflows are being increasingly used to analyze medical records with heterogeneous phenotypic, genotypic, and related medical terms to improve patient care. We performed a retrospective study using neuropathology reports from the German Neuropathology Reference Center for Epilepsy Surgery at Erlangen, Germany. This cohort included 312 patients who underwent epilepsy surgery and …

Challenges Associated With The Integration Of Immuno-Oncology Agents In Clinical Practice, Patrice Lazure, Aparna R Parikh, Neal E Ready, Marianne J Davies, Sophie Péloquin, Jeffrey M Caterino, Robert Lewandowski, Alexander J Lazar, Suzanne Murray

Faculty, Staff and Student Publications

Background: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents.

Methods: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of …

30th Annual Scientific Congress Of Hong Kong College Of Cardiology Abstracts

Journal of the Hong Kong College of Cardiology

No abstract provided.

30th Annual Scientific Congress Of Hong Kong College Of Cardiology Proceedings

Journal of the Hong Kong College of Cardiology

No abstract provided.

Neuromyelitis Optica Spectrum Disorder: Performance On Language And Cognitive Testing, Hallee Mingus

Three Minute Thesis (3MT®) at UNI

Neuromyelitis Optica Spectrum Disorder (NMOSD) Is a rare and widely unknown disease, often resulting in misdiagnosis and nonproductive therapy. It is a relapsing inflammatory demyelinating disease that affects the central nervous system and attacks the brain, resulting in severe physical &/or visual disability (Pfeuffer et al., 2017). What little knowledge we have about NMOSD, we hold an even smaller amount about its effects on speech and communication; which is what this case history study aims to answer. Due to the lack of information regarding NMOSD’s effects on an individual’s speech and communication abilities, assessments were performed in order to start …

Exploring Stakeholders' Experiences And Perceptions Regarding Barriers To Effective Surveillance Of Communicable Diseases In A Rural District Of Pakistan: A Qualitative Study, Imran Naeem Abbasi, Sameen Siddiqi, Mmna Rehana Sididiqui, Rumina Hasan

Community Health Sciences

Objective: To explore the experiences and perceptions of health system stakeholders of a rural district of Sindh, Pakistan regarding the barriers to effective surveillance of communicable diseases.
Design: This qualitative descriptive exploratory design comprised in-depth interviews. Both inductive and deductive thematic analysis was applied to identify key themes from the data.
Settings: The study was conducted in public sector healthcare facilities and the district health office of the rural district of Thatta, in Sindh province, Pakistan.
Participants: Fifteen healthcare managers and healthcare providers working in the eight public sector primary and secondary healthcare facilities were interviewed using an open-ended in-depth …

Circulating Microrna Responses To Acute Whole-Body Vibration And Resistance Exercise In Postmenopausal Women, Samuel R. Buchanan, Ryan M. Miller, Michelle Nguyen, Christopher D. Black, J. Mikhail Kellawan, Michael G. Bemben, Debra A. Bemben

Health & Human Performance Faculty Publications

Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) …

Headache Characteristics Among Patients With Epilepsy And The Association With Temporal Encephaloceles, Patricia Graese, Milad Yazdani, Zeke Campbell

Department of Neurology Faculty Papers

PURPOSE: Our aim was to determine if headaches characteristic of possible Idiopathic Intracranial Hypertension (IIH) and in general were more prevalent in patients with versus without temporal encephaloceles (TEs) among patients with epilepsy.

METHODS: Electronic medical records were reviewed retrospectively. Among 474 patients with epilepsy, 103 patients (21.7%) had at least one TE diagnosed on initial MRI or on retrospective review by a board-certified neuroradiologist, while 371 patients had no TE present. The patients were grouped into one of four categories depending on their headache characteristics (IIH-like, peri-ictal, other, or no headaches). Analysis of the categories was performed using a …

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

Self-Guided Smartphone Application To Manage Chronic Musculoskeletal Pain: A Randomized, Controlled Pilot Trial, Chao Hsing Yeh, Jennifer Kawi, Lauren Grant, Xinran Huang, Hulin Wu, Robin L Hardwicke, Paul J Christo

Faculty, Staff and Student Publications

Objective: The goal of this study is to evaluate the feasibility and efficacy of an auricular point acupressure smartphone app (mAPA) to self-manage chronic musculoskeletal pain. Methods: A prospective, longitudinal, randomized, controlled pilot trial was conducted using a three-group design (self-guided mAPA (n = 14); in-person mAPA (n = 12); and control (n = 11)). The primary outcomes included physical function and pain intensity. Results: After a 4-week APA intervention, participants in the in-person mAPA group had improved physical function of 32% immediately post-intervention and 29% at the 1M follow-up. Participants in the self-guided mAPA group had …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Clinical And In Vitro Evidence Favoring Immunoglobulin Treatment Of A Chronic Norovirus Infection In A Patient With Common Variable Immunodeficiency, Jeroen J A Van Kampen, Virgil A S H Dalm, Pieter L A Fraaij, Bas B Oude Munnink, Claudia M E Schapendonk, Ray W Izquierdo-Lara, Nele Villabruna, Khalil Ettayebi, Mary K Estes, Marion P G Koopmans, Miranda De Graaf

Faculty, Staff and Students Publications

BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.

METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced.

RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation …