Digital Commons Network^™

Troponin Is Unrelated To Outcomes In Heart Failure Patients Discharged From The Emergency Department, Gregory J Fermann, Douglas Char, Et Al

2020-Current year OA Pubs

BACKGROUND: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management.

OBJECTIVE: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED.

METHODS: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional …

Deglutarylation Of Glutaryl-Coa Dehydrogenase By Deacylating Enzyme Sirt5 Promotes Lysine Oxidation In Mice, Dhaval P Bhatt, C Allie Mills, Kristin A Anderson, Bárbara J Henriques, Tânia G Lucas, Sara Francisco, Juan Liu, Olga R Ilkayeva, Alexander E Adams, Shreyas R Kulkarni, Donald S Backos, Michael B Major, Paul A Grimsrud, Cláudio M Gomes, Matthew D Hirschey

2020-Current year OA Pubs

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show …

Association Of Prenatal Exposure To Early-Life Adversity With Neonatal Brain Volumes At Birth, Regina L Triplett, Rachel E Lean, Amisha Parikh, J Philip Miller, Dimitrios Alexopoulos, Sydney Kaplan, Dominique Meyer, Christopher Adamson, Tara A Smyser, Cynthia E Rogers, Deanna M Barch, Barbara Warner, Joan L Luby, Christopher D Smyser

2020-Current year OA Pubs

Importance: Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood.

Objective: To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding.

Design, Setting, and Participants: This prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were …

Parent-Of-Origin Effects Propagate Through Networks To Shape Metabolic Traits, Juan F Macias-Velasco, Celine L St Pierre, Jessica P Wayhart, Li Yin, Larry Spears, Mario A Miranda, Caryn Carson, Katsuhiko Funai, James M Cheverud, Clay F Semenkovich, Heather A Lawson

2020-Current year OA Pubs

Parent-of-origin effects are unexpectedly common in complex traits, including metabolic and neurological traits. Parent-of-origin effects can be modified by the environment, but the architecture of these gene-by-environmental effects on phenotypes remains to be unraveled. Previously, quantitative trait loci (QTL) showing context-specific parent-of-origin effects on metabolic traits were mapped in the F

Differential Function And Maturation Of Human Stem Cell-Derived Islets After Transplantation, Kristina G Maxwell, Michelle H Kim, Sarah E Gale, Jeffrey R Millman

2020-Current year OA Pubs

Insulin-producing stem cell-derived islets (SC-islets) provide a virtually unlimited cell source for diabetes cell replacement therapy. While SC-islets are less functional when first differentiated in vitro compared to isolated cadaveric islets, transplantation into mice has been shown to increase their maturation. To understand the effects of transplantation on maturation and function of SC-islets, we examined the effects of cell dose, transplantation strategy, and diabetic state in immunocompromised mice. Transplantation of 2 and 5, but not 0.75 million SC-islet cells underneath the kidney capsule successfully reversed diabetes in mice with pre-existing diabetes. SQ and intramuscular injections failed to reverse diabetes at …

Stronger Microstructural Damage Revealed In Multiple Sclerosis Lesions With Central Vein Sign By Quantitative Gradient Echo Mri, Victoria A Levasseur, Biao Xiang, Amber Salter, Dmitriy A Yablonskiy, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: Multiple sclerosis (MS) lesions typically form around a central vein that can be visualized with FLAIR* MRI, creating the central vein sign (CVS) which may reflect lesion pathophysiology. Herein we used gradient echo plural contrast imaging (GEPCI) MRI to simultaneously visualize CVS and measure tissue damage in MS lesions. We examined CVS in relation to tissue integrity in white matter (WM) lesions and among MS subtypes.

OBJECTIVE: We aimed to determine if CVS positive lesions were specific to MS subtype, if CVS can be detected consistently among readers using the GEPCI method, and if there were differences in tissue …

Genome-Wide Association Studies Of Metabolites In Finnish Men Identify Disease-Relevant Loci, Xianyong Yin, Adam E Locke, Erica Young, Liron Ganel, Indraniel Das, Haley Abel, Nathan O Stitziel, Et Al

Open Access Publications

Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits.

Monospecific And Bispecific Monoclonal Sars-Cov-2 Neutralizing Antibodies That Maintain Potency Against B.1.617, Lei Peng, Yingxia Hu, Madeleine C Mankowski, Ping Ren, Rita E Chen, Michael S Diamond, Et Al

Open Access Publications

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong …

Structural And Molecular Rationale For The Diversification Of Resistance Mediated By The Antibiotic_Nat Family, Peter J Stogios, Emily Bordeleau, Zhiyu Xu, Tatiana Skarina, Elena Evdokimova, Sommer Chou, Luke Diorio-Toth, Alaric W D'Souza, Sanket Patel, Gautam Dantas, Gerard D Wright, Alexei Savchenko

Open Access Publications

The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical …

Therapeutic Drug Monitoring In Perianal Fistulizing Crohn's Disease, Mir Zulqarnain, Parakkal Deepak, Andres J Yarur

Open Access Publications

Perianal fistulas are a common complication of Crohn's disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn's disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is …

Maternal Obesogenic Diet Enhances Cholestatic Liver Disease In Offspring, Michael D Thompson, Holly Hinrichs, Austin Faerber, Phillip I Tarr, Nicholas O Davidson

Open Access Publications

Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventional chow (CON) or high fat/high sucrose (HF/HS) diet and then bred them with lean males. Offspring were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 2 weeks to induce cholestasis, and a subgroup was then fed CON for an additional 10 days. Additionally, to evaluate the role of the gut microbiome, we fed antibiotic-treated mice cecal contents from CON or HF/HS offspring, …

Sorl1 Polymorphisms In Mexican Patients With Alzheimer's Disease, Danira Toral-Rios, Elizabeth Ruiz-Sánchez, Nancy Lucero Martínez Rodríguez, Marlene Maury-Rosillo, Óscar Rosas-Carrasco, Fernando Becerril-Pérez, Francisco Mena-Barranco, Rosa Carvajal-García, Daniela Silva-Adaya, Yair Delgado-Namorado, Gerardo Ramos-Palacios, Carmen Sánchez-Torres, Victoria Campos-Peña

Open Access Publications

The present study evaluated the risk effect of 12 Single Nucleotide Polymorphisms in the SORL1 gene in the Mexican population using Late-Onset Alzheimer's Disease (LOAD) and control subjects. Considering APOE as the strongest genetic risk factor for LOAD, we conducted interaction analyses between single nucleotide polymorphisms (SNPs) and the APOE genotype.

METHODS: Patients were interviewed during their scheduled visits at neurologic and geriatric clinics from different institutions. The LOAD diagnosis included neurological, geriatric, and psychiatric examinations, as well as the medical history and neuroimaging. Polymorphisms in

RESULTS: The A/A genotype in rs1784933 might be associated with an increased LOAD risk. …

Micrornas In Pulmonary Hypertension, From Pathogenesis To Diagnosis And Treatment, Junhua Xu, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang, Deming Gou

Open Access Publications

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. …

Spherical Nucleic Acids As Precision Therapeutics For The Treatment Of Cancer—From Bench To Bedside, Akanksha S Mahajan, Alexander H Stegh

Open Access Publications

Spherical Nucleic Acids (SNAs) emerged as a new class of nanotherapeutics consisting of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and in the absence of auxiliary transfection agents, enables robust uptake into tumor and immune cells through polyvalent association with cell surface pattern recognition receptors. When composed of gene-regulatory small interfering (si)RNA or immunostimulatory DNA or RNA oligonucleotides, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their "free" form. Early phase …

Predictors Of Humoral Response To Sars-Cov-2 Mrna Vaccine Bnt162b2 In Patients Receiving Maintenance Dialysis, Li Tingting, Sumanth Gandra, Kimberly A. Reske, Margaret A. Olsen, Silvana Bommarito, Candace Miller, Karl G. Hock, Claire A. Ballman, Christina Su, Na Le Dang, Jennie H. Kwon, David K. Warren, Victoria J. Fraser, Christopher W. Farnsworth

Open Access Publications

No abstract provided.

Conditional Loss Of Ikkα In Osterix + Cells Has No Effect On Bone But Leads To Age-Related Loss Of Peripheral Fat, Jennifer L Davis, Nitin Kumar Pokhrel, Linda Cox, Nidhi Rohatgi, Roberta Faccio, Deborah J Veis

Open Access Publications

NF-κB has been reported to both promote and inhibit bone formation. To explore its role in osteolineage cells, we conditionally deleted IKKα, an upstream kinase required for non-canonical NF-κB activation, using Osterix (Osx)-Cre. Surprisingly, we found no effect on either cancellous or cortical bone, even following mechanical loading. However, we noted that IKKα conditional knockout (cKO) mice began to lose body weight after 6 months of age with severe reductions in fat mass and lower adipocyte size in geriatric animals. qPCR analysis of adipogenic markers in fat pads of cKO mice indicated no difference in early differentiation, but instead markedly …

Mitochondrial Phenotypes In Genetically Diverse Neurodegenerative Diseases And Their Response To Mitofusin Activation, Xiawei Dang, Emily K Walton, Barbara Zablocka, Robert H Baloh, Michael E Shy, Gerald W Dorn Ii

Open Access Publications

Mitochondrial fusion is essential to mitochondrial fitness and cellular health. Neurons of patients with genetic neurodegenerative diseases often exhibit mitochondrial fragmentation, reflecting an imbalance in mitochondrial fusion and fission (mitochondrial dysdynamism). Charcot-Marie-Tooth (CMT) disease type 2A is the prototypical disorder of impaired mitochondrial fusion caused by mutations in the fusion protein mitofusin (MFN)2. Yet, cultured CMT2A patient fibroblast mitochondria are often reported as morphologically normal. Metabolic stress might evoke pathological mitochondrial phenotypes in cultured patient fibroblasts, providing a platform for the pre-clinical individualized evaluation of investigational therapeutics. Here, substitution of galactose for glucose in culture media was used to redirect …

Predicting Mitochondrial Dynamic Behavior In Genetically Defined Neurodegenerative Diseases, Gerald W Dorn Ii, Xiawei Dang

Open Access Publications

Mitochondrial dynamics encompass mitochondrial fusion, fission, and movement. Mitochondrial fission and fusion are seemingly ubiquitous, whereas mitochondrial movement is especially important for organelle transport through neuronal axons. Here, we review the roles of different mitochondrial dynamic processes in mitochondrial quantity and quality control, emphasizing their impact on the neurological system in Charcot-Marie-Tooth disease type 2A, amyotrophic lateral sclerosis, Friedrich's ataxia, dominant optic atrophy, and Alzheimer's, Huntington's, and Parkinson's diseases. In addition to mechanisms and concepts, we explore in detail different technical approaches for measuring mitochondrial dynamic dysfunction in vitro, describe how results from tissue culture studies may be applied to …

Adherence Enables Neisseria Gonorrhoeae To Overcome Zinc Limitation Imposed By Nutritional Immunity Proteins, Jocelyn C Ray, Asya Smirnov, Stavros A Maurakis, Simone A Harrison, Eugene Ke, Walter J Chazin, Cynthia Nau Cornelissen, Alison K Criss

Open Access Publications

Neisseria gonorrhoeae (Gc) must overcome the limitation of metals such as zinc to colonize mucosal surfaces in its obligate human host. While the zinc-binding nutritional immunity proteins calprotectin (S100A8/A9) and psoriasin (S100A7) are abundant in human cervicovaginal lavage fluid, Gc possesses TonB-dependent transporters TdfH and TdfJ that bind and extract zinc from the human version of these proteins, respectively. Here we investigated the contribution of zinc acquisition to Gc infection of epithelial cells of the female genital tract. We found that TdfH and TdfJ were dispensable for survival of strain FA1090 Gc that was associated with Ect1 human immortalized epithelial …

Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian

Open Access Publications

Viruses are one of the most important concerns for human health, and overcoming viral infections is a worldwide challenge. However, researchers have been trying to manipulate viral genomes to overcome various disorders, including cancer, for vaccine development purposes. CRISPR (clustered regularly interspaced short palindromic repeats) is becoming one of the most functional and widely used tools for RNA and DNA manipulation in multiple organisms. This approach has provided an unprecedented opportunity for creating simple, inexpensive, specific, targeted, accurate, and practical manipulations of viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1), and vaccinia virus. Furthermore, …

Metronidazole Treatment Rapidly Reduces Genital Inflammation Through Effects On Bacterial Vaginosis-Associated Bacteria Rather Than Lactobacilli, Eric Armstrong, Hilary Reno, Et Al.

2020-Current year OA Pubs

BackgroundBacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this reduction is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species.METHODSTo evaluate the short-term effect of standard BV treatment on genital immunology and the vaginal microbiota, vaginal swabs were collected immediately before and after metronidazole treatment for BV and analyzed with multiplex ELISA, metagenomic sequencing, and quantitative PCR.RESULTSTopical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, …

Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan

Open Access Publications

Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies …

Towards A Biological Definition Of Ards: Are Treatable Traits The Solution?, Lieuwe D J Bos, John G Laffey, Lorraine B Ware, Nanon F L Heijnen, Pratik Sinha, Brijesh Patel, Matthieu Jabaudon, Julie A Bastarache, Daniel F Mcauley, Charlotte Summers, Carolyn S Calfee, Manu Shankar-Hari

2020-Current year OA Pubs

The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying …

Pftaire Kinase L63 Interactor 1a (Pif1a Protein) Is Required For Actin Cone Movement During Spermatid Individualization In Drosophila Melanogaster, Harrison D Pravder, Dorota Grabowska, Kaushik Roychoudhury, Betty Zhang, Deborah Frank, Przemysław Zakrzewski, Marta Lenartowska, Kathryn G Miller

Open Access Publications

A useful model for determining the mechanisms by which actin and actin binding proteins control cellular architecture is the

Dose-Finding Study Of Ibrutinib And Venetoclax In Relapsed Or Refractory Mantle Cell Lymphoma, Craig A Portell, Nolan A Wages, Brad S Kahl, Lihua E Budde, Robert W Chen, Jonathon B Cohen, Nikole E Varhegyi, Gina R Petroni, Michael E Williams

Open Access Publications

Relapsed Mantle cell lymphoma (MCL) is often treated with Bruton's tyrosine kinase inhibitors (BTKi); however, post-BTKi relapse can be challenging. Adding venetoclax (VEN) to ibrutinib (IBR) has shown synergy in preclinical MCL models. Prior MCL studies of the combination show promising efficacy but have conducted limited dose finding. We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual reassessment method of 6 combinations of IBR (280 mg, 420 mg, and 560 mg by mouth daily) and VEN (max dose of 200 mg and 400 mg by mouth daily). Eligible participants were not previously exposed …

Strainge: A Toolkit To Track And Characterize Low-Abundance Strains In Complex Microbial Communities, Lucas R Van Dijk, Bruce J Walker, Timothy J Straub, Colin J Worby, Alexandra Grote, Henry L Schreiber 4th, Christine Anyansi, Amy J Pickering, Scott J Hultgren, Abigail L Manson, Thomas Abeel, Ashlee M Earl

2020-Current year OA Pubs

Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.

Structure Of The Wilson Disease Copper Transporter Atp7b, Ryan M Bitter, Secheol Oh, Zengqin Deng, Suhaila Rahman, Richard K Hite, Peng Yuan

Open Access Publications

ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains a P-type ATPase core consisting of a membrane transport domain and three cytoplasmic domains, the A, P, and N domains, and a unique amino terminus comprising six consecutive metal-binding domains. Here, we present a cryo-electron microscopy structure of frog ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues …

Circular Rna Detection Identifies Circpsen1 Alterations In Brain Specific To Autosomal Dominant Alzheimer's Disease, Hsiang-Han Chen, Abdallah Eteleeb, Ciyang Wang, Maria Victoria Fernandez, John P Budde, Kristy Bergmann, Joanne Norton, Fengxian Wang, Curtis Ebl, John C Morris, Richard J Perrin, Randall J Bateman, Eric Mcdade, Chengjie Xiong, Alison Goate, Martin Farlow, Jasmeer Chhatwal, Peter R Schofield, Helena Chui, Oscar Harari, Carlos Cruchaga, Laura Ibanez, Dominantly Inherited Alzheimer Network

2020-Current year OA Pubs

BACKGROUND: Autosomal-dominant Alzheimer's disease (ADAD) is caused by pathogenic mutations in APP, PSEN1, and PSEN2, which usually lead to an early age at onset (<  65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD.

METHODS: We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for PSEN1, PSEN2 and APP genes. Only circPSEN1 passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed in-silico functional analyses using the Circular RNA interactome website and DIANA mirPath …

Prediagnosis Leisure-Time Physical Activity And Lung Cancer Survival: A Pooled Analysis Of 11 Cohorts, Jae Jeong Yang, Yikyung Park, Et Al.

2020-Current year OA Pubs

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients.

METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum …

Sex-Based Differences In Functional Brain Activity During Working Memory In Survivors Of Pediatric Acute Lymphoblastic Leukemia, Kellen Gandy, Matthew A Scoggins, Nicholas Phillips, Ellen Van Der Plas, Slim Fellah, Lisa M Jacola, Ching-Hon Pui, Melissa M Hudson, Wilburn E Reddick, Ranganatha Sitaram, Kevin R Krull

2020-Current year OA Pubs

BACKGROUND: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone.

METHODS: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, …