Digital Commons Network^™

Cognitive Function Following Diabetic Ketoacidosis In Young Children With Type 1 Diabetes, Simona Ghetti, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.

METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, …

Polygenic Risk Score Penetrance & Recurrence Risk In Familial Alzheimer Disease, Min Qiao, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease.

METHODS: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE-ε4 carriers …

Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD

PURPOSE: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.

METHODS: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.

RESULTS: In a subset of the dataset aligned …

Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and …

Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied …

Quantitative Determination Of Slc2a1 Variant Functional Effects In Glut1 Deficiency Syndrome, Naeimeh Tayebi, Brian Leon-Ricardo, Kevin Mccall, Elvisa Mehinovic, Kristin Engelstad, Vincent Huynh, Tychele N Turner, Judy Weisenberg, Liu L Thio, Paul Hruz, Robin S B Williams, Darryl C De Vivo, Vincent Petit, Gabe Haller, Christina A Gurnett

2020-Current year OA Pubs

OBJECTIVE: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.

METHODS: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD …

Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al.

2020-Current year OA Pubs

BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy.

METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to …

Provisional Practice Recommendation For The Management Of Myopathy In Vcp-Associated Multisystem Proteinopathy, Bhaskar Roy, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on …

Treatment And Disposal Practices Of Pharmaceutical Effluent Containing Potential Antibiotic Residues In Two States In India And Perceptions Of Various Stakeholders On Contribution Of Pharmaceutical Effluent To Antimicrobial Resistance: A Qualitative Study, Anita Kotwani, Ajita Kapur, Mihir Chauhan, Sumanth Gandra

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance (AMR) is a looming pandemic, demanding prompt actions to avert catastrophic consequences. Effluents from pharmaceutical industries containing antimicrobial residues could serve as one of the entry points of these drugs to the environment. This qualitative study explores the treatment and disposal practices of pharmaceutical effluent (PE) containing potential antibiotic residues (ARs) by interviewing major stakeholders. In addition, we assessed their knowledge and perception on contribution of PE to AMR.

METHODS: The study was conducted in the two Indian states, Haryana and Telangana and at the federal level. Data was collected by semi-structured in-depth interviews of 29 participants …

A Phase 1 First-In-Human Study Of Gs-0189, An Anti-Signal Regulatory Protein Alpha (Sirpα) Monoclonal Antibody, In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (Nhl), Mayur Narkhede, Nancy L Bartlett, Sami Ibrahimi, Leslie Popplewell, Anna Seto, Jamie Bates, Yeonju Lee, Vaishnavi Ganti, Ling Han, Tianling Chen, Manish R Patel

2020-Current year OA Pubs

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS-0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); …

Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu

2020-Current year OA Pubs

Identifying complete response (CR) after rectal cancer preoperative treatment is critical to deciding subsequent management. Imaging techniques, including endorectal ultrasound and MRI, have been investigated but have low negative predictive values. By imaging post-treatment vascular normalization using photoacoustic microscopy, we hypothesize that co-registered ultrasound and photoacoustic imaging will better identify complete responders. In this study, we used

Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang

2020-Current year OA Pubs

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …

Steady-State Memory-Phenotype Conventional Cd4+ T Cells Exacerbate Autoimmune Neuroinflammation In A Bystander Manner Via The Bhlhe40/Gm-Csf Axis, Min-Ji Cho, Hong-Gyun Lee, Jae-Won Yoon, Gil-Ran Kim, Ja-Hyun Koo, Reshma Taneja, Brian T Edelson, You Jeong Lee, Je-Min Choi

2020-Current year OA Pubs

Memory-phenotype (MP) CD4

Leveraging Innovation To Mitigate Risk During Heart Surgery, Marc R Moon, Puja Kachroo

2020-Current year OA Pubs

No abstract provided.

Influence Of Genomic Landscape On Cancer Immunotherapy For Newly Diagnosed Ovarian Cancer: Biomarker Analyses From The Imagyn050 Randomized Clinical Trial, Charles N Landen, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.

PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations …

Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.

EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome …

Influence Of Environmental Temperature And Heatwaves On Surgical Site Infection After Hip And Knee Arthroplasty: A Nationwide Study, L Damonti, A Atkinson, L Fontannaz, J P Burnham, P Jent, N Troillet, A Widmer, J Marschall, For Swissnoso, National Center For Infection Control

2020-Current year OA Pubs

BACKGROUND: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves.

AIM: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty.

METHODS: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. …

Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

PURPOSE: Economic empowerment and family strengthening interventions have shown promise for improving psychosocial well-being in a range of populations. This study investigates the effect of a combination economic and family strengthening intervention on psychosocial well-being among Ugandan adolescent girls and young women (AGYW).

METHODS: We harnessed data from a three-arm cluster randomized controlled trial among AGYW aged 14-17 years in 47 Ugandan secondary schools. Schools were randomized to either a youth development account intervention (YDA) [N = 16 schools], YDA plus a multiple family group intervention (YDA + MFG) [N = 15 schools], or bolstered standard of care (BSOC) [N …

Circulating Markers Of Microbial Translocation And Host Response To Bacteria With Risk Of Colorectal Cancer: A Prospective, Nested Case-Control Study In Men, Mengyao Shi, Xiaoyu Zong, Jinhee Hur, Brenda M Birmann, Otoniel Martinez-Maza, Marta Epeldegui, Andrew T Chan, Edward L Giovannucci, Yin Cao

2020-Current year OA Pubs

BACKGROUND: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited.

METHODS: We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 …

Sars-Cov-2 Vaccination In The First Year After Allogeneic Hematopoietic Cell Transplant: A Prospective, Multicentre, Observational Study, Joshua A Hill, Peter Westervelt, Et Al.

2020-Current year OA Pubs

BACKGROUND: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood.

METHODS: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. …

Pregnancy And Neonatal Outcomes Among Women With Early-Onset Colorectal Cancer: A Nationwide Case-Control Study, Yin Cao, Stephanie Zhao, Tomas S Bexelius, Jonas Söderling, Mengyao Shi, Bjorn Roelstraete, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

BACKGROUND: Early-onset colorectal cancer has risen worldwide, leaving more women with colorectal cancer at reproductive ages. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among women with early-onset colorectal cancer.

METHODS: We conducted a nationwide, matched case-control study of maternal/pregnancy outcomes including pre-eclampsia and Cesarean delivery (C-section) as well as neonatal outcomes including preterm birth among 207 births in women with early-onset colorectal cancer (ages 18-49) and 1019 births in women without colorectal cancer in Sweden (1992-2019). Early-onset colorectal cancer cases were identified through the Cancer Register, and outcome data were retrieved through linkage to Medical …

Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa

2020-Current year OA Pubs

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year.

OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery.

STUDY DESIGN: The Medicare 5% Limited Data Set was queried from …

Biochemical Network Analysis Of Protein-Protein Interactions To Follow-Up T1 Bladder Cancer Patients, Luís B Carvalho, José Luis Capelo Martínez, Carlos Lodeiro, Rafael Bento, Rajiv Dhir, Jeremiah J Morrissey, Luis Campos Pinheiro, Mariana Medeiros, Hugo M Santos

2020-Current year OA Pubs

Bladder cancer (BCa) is a prevalent disease with a high risk of aggressive recurrence in T1-stage patients. Despite the efforts to anticipate recurrence, a reliable method has yet to be developed. In this work, we employed high-resolution mass spectrometry to compare the urinary proteome of T1-stage BCa patients with recurring versus non-recurring disease to uncover actionable clinical information predicting recurrence. All patients were diagnosed with T1-stage bladder cancer between the ages of 51 and 91, and urine samples were collected before medical intervention. Our results suggest that the urinary myeloperoxidase to cubilin ratio could be used as a new tool …

Mzion Enables Deep And Precise Identification Of Peptides In Data-Dependent Acquisition Proteomics, Qiang Zhang

2020-Current year OA Pubs

Sensitive and reliable identification of proteins and peptides pertains the basis of proteomics. We introduce Mzion, a new database search tool for data-dependent acquisition (DDA) proteomics. Our tool utilizes an intensity tally strategy and achieves generally a higher performance in terms of depth and precision across 20 datasets, ranging from large-scale to single-cell proteomics. Compared to several other search engines, Mzion matches on average 20% more peptide spectra at tryptic enzymatic specificity and 80% more at no enzymatic specificity from six large-scale, global datasets. Mzion also identifies more phosphopeptide spectra that can be explained by fewer proteins, demonstrated by six …

Utilizing Computed Tomography Volumetry For Size Matching Prior To Lung Transplantation: A Case Series, Hailey M. Shepherd, Khashayar Farahnak, M. Shea Harrison, C. Corbin Frye, Gary F. Marklin, Andrew J. Bierhals, Ramsey R. Hachem, Chad A. Witt, Rodrigo V. Guillamet, Derek E. Byers, Benjamin D. Kozower, Bryan F. Meyers, Ruben G. Nava, G. Alexander Patterson, Daniel Kreisel, Varun Puri

2020-Current year OA Pubs

BACKGROUND: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value.

CASE DESCRIPTION: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly …

Abrogation Of Map4k4 Protein Function Causes Congenital Anomalies In Humans And Zebrafish, Victoria Patterson, Dorothy K Grange, Et Al.

2020-Current year OA Pubs

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S Weinstock, C Charles Gu, Et Al.

2020-Current year OA Pubs

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …

Definitive Chemoradiation Associated With Improved Survival Outcomes In Patients With Synchronous Oligometastatic Esophageal Cancer, Thomas Matoska, Anjishnu Banerjee, Aditya Shreenivas, Lauren Jurkowski, Monica E Shukla, Elizabeth M Gore, Paul Linsky, Mario Gasparri, Ben George, Candice Johnstone, David Johnstone, Lindsay L Puckett

2020-Current year OA Pubs

BACKGROUND: The study of oligometastatic esophageal cancer (EC) is relatively new. Preliminary data suggests that more aggressive treatment regimens in select patients may improve survival rates in oligometastatic EC. However, the consensus recommends palliative treatment. We hypothesized that oligometastatic esophageal cancer patients treated with a definitive approach (chemoradiotherapy [CRT]) would have improved overall survival (OS) compared to those treated with a purely palliative intent and historical controls.

METHODS: Patients diagnosed with synchronous oligometastatic (any histology, ≤5 metastatic foci) esophageal cancer treated in a single academic hospital were retrospectively analyzed and divided into definitive and palliative treatment groups. Definitive CRT was …

Ebolavirus Species-Specific Interferon Antagonism Mediated By Vp24, Palaniappan Ramanathan, Bersabeh Tigabu, Rodrigo I Santos, Philipp A Ilinykh, Natalia Kuzmina, Olivia A Vogel, Naveen Thakur, Hamza Ahmed, Chao Wu, Gaya K Amarasinghe, Christopher F Basler, Alexander Bukreyev

2020-Current year OA Pubs

Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic, and Reston (RESTV) is not known to cause a disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously, we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with a reduced inhibition in IFN-I signaling. We hypothesized that modification of eVP24-karyopherin …

Benchmarking Hospital Practices And Policies On Intrahospital Neurocritical Care Transport: The Safe-Neuro-Transport Study, Kapil G Zirpe, Bhunyawee Alunpipatthanachai, Nassim Matin, Bernice G Gulek, Patricia A Blissitt, Katherine Palmieri, Kathryn Rosenblatt, Umeshkumar Athiraman, Suneeta Gollapudy, Marie Angele Theard, Sarah Wahlster, Monica S Vavilala, Abhijit V Lele, Safe-Neuro-Transport Collaborators

2020-Current year OA Pubs

An electronic survey was administered to multidisciplinary neurocritical care providers at 365 hospitals in 32 countries to describe intrahospital transport (IHT) practices of neurocritically ill patients at their institutions. The reported IHT practices were stratified by World Bank country income level. Variability between high-income (HIC) and low/middle-income (LMIC) groups, as well as variability between hospitals within countries, were expressed as counts/percentages and intracluster correlation coefficients (ICCs) with a 95% confidence interval (CI). A total of 246 hospitals (67% response rate;