Medicine and Health Sciences Commons^™

Protection Of Messenger Rna Vaccines Against Hospitalized Coronavirus Disease 2019 In Adults Over The First Year Following Authorization In The United States, Mark W Tenforde, Hilary M Babcock, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.

METHODS: Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing …

Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting Pd-L1 And Tgf-Β, In Patients With Pretreated Colorectal Cancer: Results From A Phase I Trial, Alexander Spira, Michael S Wertheim, Edward J Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L Gulley, Scott Kopetz

2020-Current year OA Pubs

Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor β (TGF-β) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received bintrafusp alfa …

Structures Of Human Gastrin-Releasing Peptide Receptors Bound To Antagonist And Agonist For Cancer And Itch Therapy, Shuman Peng, Yuting Zhan, Dongqi Zhang, Lu Ren, Anqi Chen, Zhou-Feng Chen, Haitao Zhang

2020-Current year OA Pubs

Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog …

Prognostic Significance Of Early Platelet Dynamics In Staphylococcus Aureus Bacteremia, Rachid Douglas-Louis, Mimi Lou, Brian Lee, Emi Minejima, Juliane Bubeck-Wardenburg, Annie Wong-Beringer

2020-Current year OA Pubs

BACKGROUND: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB).

METHOD: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence.

RESULTS: Among the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2-3 following SAB onset, and Day 4 was a determining …

Fifty Years Of Global Cardiovascular Research In Africa: A Scientometric Analysis, 1971 To 2021, Jean Jacques Noubiap, Dominic Millenaar, Dike Ojji, Q Eileen Wafford, Christian Ukena, Michael Böhm, Karen Sliwa, Mark D Huffman, Felix Mahfoud

2020-Current year OA Pubs

Background To analyze the quantity and impact of cardiovascular research done in Africa or coauthored by researchers based in Africa, their determinants, and the patterns of research collaboration. Methods and Results We retrieved data from Web of Science and additional sources. We analyzed temporal trends from 1971 to 2021 and geographical distribution, research impact using country-level h-index, international research cooperation, and associations of research quantity and quality using linear regression. The annual volume of cardiovascular research from Africa has increased from 4 publications in 1971 to 3867 in 2020 and currently represents ~3% of the global cardiovascular research output. Authors …

Evaluation Of Apparent Diffusion Coefficient Repeatability And Reproducibility For Preclinical Mris Using Standardized Procedures And A Diffusion-Weighted Imaging Phantom, Dariya Malyarenko, Ghoncheh Amouzandeh, Stephen Pickup, Rong Zhou, Henry Charles Manning, Seth T Gammon, Kooresh I Shoghi, James D Quirk, Renuka Sriram, Peder Larson, Michael T Lewis, Robia G Pautler, Paul E Kinahan, Mark Muzi, Thomas L Chenevert

2020-Current year OA Pubs

Relevant to co-clinical trials, the goal of this work was to assess repeatability, reproducibility, and bias of the apparent diffusion coefficient (ADC) for preclinical MRIs using standardized procedures for comparison to performance of clinical MRIs. A temperature-controlled phantom provided an absolute reference standard to measure spatial uniformity of these performance metrics. Seven institutions participated in the study, wherein diffusion-weighted imaging (DWI) data were acquired over multiple days on 10 preclinical scanners, from 3 vendors, at 6 field strengths. Centralized versus site-based analysis was compared to illustrate incremental variance due to processing workflow. At magnet isocenter, short-term (intra-exam) and long-term (multiday) …

Ion Channel Regulation Of Gut Immunity, Jing Feng, Zili Xie, Hongzhen Hu

2020-Current year OA Pubs

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut's immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been …

Widespread Contribution Of Transposable Elements To The Rewiring Of Mammalian 3d Genomes, Mayank N K Choudhary, Kara Quaid, Xiaoyun Xing, Heather Schmidt, Ting Wang

2020-Current year OA Pubs

Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We …

The P97-Ubxd8 Complex Regulates Er-Mitochondria Contact Sites By Altering Membrane Lipid Saturation And Composition, Rakesh Ganji, Joao A Paulo, Yuecheng Xi, Ian Kline, Jiang Zhu, Christoph S Clemen, Conrad C Weihl, John G Purdy, Steve P Gygi, Malavika Raman

2020-Current year OA Pubs

The intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-Mitochondria contact sites (ERMCS) is a platform for critical cellular processes, particularly lipid synthesis. How contacts are remodeled and the impact of altered contacts on lipid metabolism remains poorly understood. We show that the p97 AAA-ATPase and its adaptor ubiquitin-X domain adaptor 8 (UBXD8) regulate ERMCS. The p97-UBXD8 complex localizes to contacts and its loss increases contacts in a manner that is dependent on p97 catalytic activity. Quantitative proteomics and lipidomics of ERMCS demonstrates alterations in proteins regulating lipid metabolism and a significant change in membrane lipid saturation …

Improving Communication In Intensive Care Unit To Ward Transitions: Protocol For Multisite National Implementation Of The Icu-Pause Handoff Tool, Elle Mizuki Fukui, Patrick G Lyons, Emily Harris, Emma K Mccune, Juan C Rojas, Lekshmi Santhosh

2020-Current year OA Pubs

BACKGROUND: The intensive care unit (ICU)-ward transfer poses a particularly high-risk period for patients. The period after transfer has been associated with adverse events and additional work for care teams related to miscommunication or omission of information. Standardized handoff processes have been found to reduce communication errors and adverse patient events in other clinical environments but are understudied at the ICU-ward interface. We previously developed an electronic ICU-ward transfer tool, ICU-PAUSE, which embeds the key elements and diagnostic reasoning to facilitate a safe transfer of care at ICU discharge.

OBJECTIVE: The aim of this study is to evaluate the implementation …

Antitumour Activity Of Neratinib In Patients With Her2-Mutant Advanced Biliary Tract Cancers, James J Harding, Haeseong Park, Et Al.

2020-Current year OA Pubs

HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has activity in HER2-mutant tumours. SUMMIT is an open-label, single-arm, multi-cohort, phase 2, 'basket' trial of neratinib in patients with solid tumours harbouring oncogenic HER2 somatic mutations (ClinicalTrials.gov: NCT01953926). The primary objective of the BTC cohort, which is now complete, is first objective response rate (ORR) to neratinib 240 mg orally daily. Secondary objectives include confirmed ORR, clinical benefit rate, progression-free survival, duration of response, overall survival, safety and tolerability. Genomic analyses were exploratory. …

Preclinical Efficacy Of A Parp-1 Targeted Auger-Emitting Radionuclide In Prostate Cancer, Sreeja Sreekumar, Dong Zhou, Cedric Mpoy, Elsa Schenk, Jalen Scott, Jeffrey M Arbeit, Jinbin Xu, Buck E Rogers

2020-Current year OA Pubs

There is an unmet need for better therapeutic strategies for advanced prostate cancer. Poly (ADP-ribose) polymerase-1 (PARP-1) is a chromatin-binding DNA repair enzyme overexpressed in prostate cancer. This study evaluates whether PARP-1, on account of its proximity to the cell's DNA, would be a good target for delivering high-linear energy transfer Auger radiation to induce lethal DNA damage in prostate cancer cells. We analyzed the correlation between PARP-1 expression and Gleason score in a prostate cancer tissue microarray. A radio-brominated Auger emitting inhibitor ([

Microbes, Histology, Blood Analysis, Enterotoxins, And Cytokines: Findings From The Aserf Systemic Symptoms In Women-Biospecimen Analysis Study: Part 3, Patricia Mcguire, Caroline Glicksman, Roger Wixtrom, C James Sung, Robert Hamilton, Marisa Lawrence, Melinda Haws, Sarah Ferenz, Marshall Kadin

2020-Current year OA Pubs

BACKGROUND: There has been an increasing need to acquire rigorous scientific data to answer the concerns of physicians, patients, and the FDA regarding the self-reported illness identified as breast implant illness (BII). There are no diagnostic tests or specific laboratory values to explain the reported systemic symptoms described by these patients.

OBJECTIVES: The aim of this study was to determine if there are quantifiable laboratory findings that can be identified in blood, capsule tissue pathology, or microbes that differentiate women with systemic symptoms they attribute to their implants from 2 control groups.

METHODS: A prospective blinded study enrolled 150 subjects …

Netprophet 3: A Machine Learning Framework For Transcription Factor Network Mapping And Multi-Omics Integration, Dhoha Abid, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: Many methods have been proposed for mapping the targets of transcription factors (TFs) from gene expression data. It is known that combining outputs from multiple methods can improve performance. To date, outputs have been combined by using either simplistic formulae, such as geometric mean, or carefully hand-tuned formulae that may not generalize well to new inputs. Finally, the evaluation of accuracy has been challenging due to the lack of genome-scale, ground-truth networks.

RESULTS: We developed NetProphet3, which combines scores from multiple analyses automatically, using a tree boosting algorithm trained on TF binding location data. We also developed three independent, …

Ssris Differentially Modulate The Effects Of Pro-Inflammatory Stimulation On Hippocampal Plasticity And Memory Via Sigma 1 Receptors And Neurosteroids, Yukitoshi Izumi, Angela M Reiersen, Eric J Lenze, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely to lipopolysaccharide (LPS), a strong pro-inflammatory stimulus, basal synaptic transmission in the CA1 region remains intact, but induction of long-term potentiation (LTP), a form of synaptic plasticity thought to contribute to learning and memory, is completely …

The Efficacy Of A Posterior Approach To Surgical Correction For Neglected Idiopathic Scoliosis: A Comparative Analysis According To Health-Related Quality Of Life, Pulmonary Function, Back Pain And Sexual Function, Pawel Grabala, Ilkka J Helenius, Jacob M Buchowski, Suken A Shah

2020-Current year OA Pubs

BACKGROUND: This study aimed to evaluate the treatment outcomes of severe idiopathic scoliosis (IS) and hypothesized that surgical treatment would have a superior impact on the health-related quality of life (HRQoL), pulmonary function (PF), back pain, and sexual function.

METHODS: We retrospectively reviewed 195 consecutive patients with IS classified into severe (SG) and moderate groups (MG) with a minimum follow-up of two years.

RESULTS: The mean preoperative curve was 131° and 60° in the SG and MG, respectively. The mean preoperative flexibility in the bending films averaged between 22% in the SG and 41% in the MG. After definitive surgery, …

Presence Of Trans-Fatty Acids Containing Ingredients In Pre-Packaged Foods And The Availability Of Reported Trans-Fat Levels In Kenya And Nigeria, Liping Huang, Adedayo E Ojo, Judith Kimiywe, Alex Kibet, Boni M Ale, Clementina E Okoro, Jimmy Louie, Fraser Taylor, Mark D Huffman, Dike B Ojji, Jason H Y Wu, Matti Marklund

2020-Current year OA Pubs

In most African countries, the prevalence of industrially produced

Multi-Ancestry Transcriptome-Wide Association Analyses Yield Insights Into Tobacco Use Biology And Drug Repurposing, Fang Chen, Lisa De Las Fuentes, Et Al.

2020-Current year OA Pubs

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with …

Brainwave: A Flexible Method For Noninvasive Stimulation Of Brain Rhythms Across Species, Matthew K. Attokaren, Nuri Jeong, Lou Blanpain, Abigail L. Paulson, Kristie M. Garza, Ben Borron, Michael Walelign, Jon Willie, Annabelle C. Singer

2020-Current year OA Pubs

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are limited. Accordingly, we recently introduced a noninvasive stimulation approach using flickering lights and sounds ("flicker"). Flicker drives rhythmic activity in deep and superficial brain regions. Gamma flicker spurs immune function, clears pathogens, and rescues memory performance in mice with amyloid pathology. Here, we present substantial improvements to this approach that is flexible, user-friendly, and generalizable across multiple experimental settings and species. We present novel open-source …

Functional And Clinical Studies Reveal Pathophysiological Complexity Of Clcn4-Related Neurodevelopmental Condition, Elizabeth E Palmer, Linda J Richards, Et Al.

2020-Current year OA Pubs

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on …

Knockout Of Tsc2 In Nav1.8+ Neurons Predisposes To The Onset Of Normal Weight Obesity, Jennifer M Brazill, David Shin, Kristann Magee, Anurag Majumdar, Ivana R Shen, Valeria Cavalli, Erica L Scheller

2020-Current year OA Pubs

OBJECTIVE: Obesity and nutrient oversupply increase mammalian target of rapamycin (mTOR) signaling in multiple cell types and organs, contributing to the onset of insulin resistance and complications of metabolic disease. However, it remains unclear when and where mTOR activation mediates these effects, limiting options for therapeutic intervention. The objective of this study was to isolate the role of constitutive mTOR activation in Nav1.8-expressing peripheral neurons in the onset of diet-induced obesity, bone loss, and metabolic disease.

METHODS: In humans, loss of function mutations in tuberous sclerosis complex 2 (TSC2) lead to maximal constitutive activation of mTOR. To mirror this in …

Sex-Specific Hypnotic Effects Of The Neuroactive Steroid (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile Are Mediated By Peripheral Metabolism Into An Active Hypnotic Steroid, Francesca M Manzella, Omar H Cabrera, Davis Wilkey, Brier Fine-Raquet, Jelena Klawitter, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

2020-Current year OA Pubs

BACKGROUND: The novel synthetic neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) blocks T-type calcium channels but does not directly modulate neuronal γ-aminobutyric acid type A (GABA

METHODS: We used a combination of behavioural loss of righting reflex, neuroendocrine, pharmacokinetic, in vitro patch-clamp electrophysiology, and in vivo electrophysiological approaches in wild-type mice and in genetic knockouts of the Ca

RESULTS: Adult male mice were less sensitive to the hypnotic effects of 3β-OH compared with female mice, and these differences appeared during development. Adult males had higher 3β-OH brain concentrations despite being less sensitive to its hypnotic effects. Females metabolised 3β-OH into the active GABA …

Modulation Of Trpv4 Protects Against Degeneration Induced By Sustained Loading And Promotes Matrix Synthesis In The Intervertebral Disc, Garrett W D Easson, Alireza Savadipour, Akila Anandarajah, Leanne E Iannucci, Spencer P Lake, Farshid Guilak, Simon Y Tang

2020-Current year OA Pubs

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 …

The Ntpase Activity Of The Double Fyve Domain-Containing Protein 1 Regulates Lipid Droplet Metabolism., Victoria A. Ismail, Teri Naismith, David J. Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks and therefore play a central role in cellular metabolism. However, the molecular factors and underlying mechanisms that regulate the growth and degradation of LDs are poorly understood. It has emerged that proteins that establish contacts between LDs and the endoplasmic reticulum play a critical role in regulating LD metabolism. Recently, the autophagy-related protein, double FYVE domain-containing protein 1 (DFCP1/ZFYVE1) was shown to reside at the interface of the endoplasmic reticulum and LDs, however, little is known about the …

The Tetraspanin Transmembrane Protein Cd53 Mediates Dyslipidemia And Integrates Inflammatory And Metabolic Signaling In Hepatocytes, Cassandra B Higgins, Joshua A Adams, Matthew H Ward, Zev J Greenberg, Małgorzata Milewska, Jiameng Sun, Yiming Zhang, Luana Chiquetto Paracatu, Qian Dong, Samuel Ballentine, Weikai Li, Ilona Wandzik, Laura G Schuettpelz, Brian J Debosch

2020-Current year OA Pubs

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction …

In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel

2020-Current year OA Pubs

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought …

The Insurance Landscape For Implant- And Autologous-Based Breast Reconstruction In The United States, Louisa C. Boyd, Jason A. Greenfield, Sravya S. Ainapurapu, Rachel Skladman, Gary Skolnick, Durai Sundaramoorthi, Justin M. Sacks

2020-Current year OA Pubs

UNLABELLED: Insurance coverage of postmastectomy breast reconstruction is mandated in America, regardless of reconstructive modality. Despite enhanced patient-reported outcomes, autologous reconstruction is utilized less than nonautologous reconstruction nationally. Lower reimbursement from Medicare and Medicaid may disincentivize autologous-based reconstruction. This study examines the impact of insurance and sociodemographic factors on breast reconstruction.

METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample Database from 2014 to 2017 was performed. International Classification of Diseases Clinical Modification and Procedure Coding System codes were used to identify patients for inclusion. De-identified sociodemographic and insurance data were analyzed using

RESULTS: In …

Genetic And Environmental Variation In Continuous Phenotypes In The Abcd Study®, Hermine H M Maes, Dana M Lapato, J Eric Schmitt, Monica Luciana, Marie T Banich, James M Bjork, John K Hewitt, Pamela A Madden, Andrew C Heath, Deanna M Barch, Wes K Thompson, William G Iacono, Michael C Neale

2020-Current year OA Pubs

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can …

A Simple Point-Of-Care Assay Accurately Detects Anti-Spike Antibodies After Sars-Cov-2 Vaccination, Sarah E Greene, Yuefang Huang, Wooseob Kim, Mariel J Liebeskind, Vinay Chandrasekaran, Zhuoming Liu, Parakkal Deepak, Michael A Paley, Daphne Lew, Mary C Nakamura, Jane A O'Hallaran, Rachel M Presti, Sean P J Whelan, William J Buchser, Alfred H J Kim, Gary J Weil, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination.

METHODS: We compared results obtained with the COVIBLOCK Covid-19 LFA to those obtained by anti-spike (S) ELISA.

RESULTS: The LFA detected anti-S antibodies in 29 of 29 (100%) of the immunocompetent and 110 of 126 (87.3%) of the CID participants after vaccination. Semiquantitative LFA scores were statistically significantly lower in samples from immunosuppressed participants, and were significantly correlated with anti-S antibody …

Do We Need Patient-Specific Qa For Adaptively Generated Plans? Retrospective Evaluation Of Delivered Online Adaptive Treatment Plans On Varian Ethos, Xiaodong Zhao, Dennis N Stanley, Carlos E Cardenas, Joseph Harms, Richard A Popple

2020-Current year OA Pubs

BACKGROUND: The clinical introduction of dedicated treatment units for online adaptive radiation therapy (OART) has led to widespread adoption of daily adaptive radiotherapy. OART allows for rapid generation of treatment plans using daily patient anatomy, potentially leading to reduction of treatment margins and increased normal tissue sparing. However, the OART workflow does not allow for measurement of patient-specific quality assurance (PSQA) during treatment delivery sessions and instead relies on secondary dose calculations for verification of adapted plans. It remains unknown if independent dose verification is a sufficient surrogate for PSQA measurements.

PURPOSE: To evaluate the plan quality of previously treated …