Medicine and Health Sciences Commons^™

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael D Chuong, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

Associations Between Early Trajectories Of Amygdala Development And Later School-Age Anxiety In Two Longitudinal Samples, Catherine A Burrows, Kelly N Botteron, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In …

Functional Network Disorganization And Cognitive Decline Following Fractionated Whole-Brain Radiation In Mice, Benjamin A. Seitzman, Francisco J. Reynoso, Timothy J. Mitchell, Annie R. Bice, Anmol Jarang, Xiaodan Wang, Cedric Mpoy, Lori Strong, Buck E. Rogers, Carla M. Yuede, Joshua B. Rubin, Stephanie M. Perkins, Adam Q. Bauer

2020-Current year OA Pubs

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of …

Angptl3 Deficiency Impairs Lipoprotein Production And Produces Adaptive Changes In Hepatic Lipid Metabolism, Kendall H Burks, Yan Xie, In-Hyuk Jung, Sandip Mukherjee, Paul Lee, Upasana Pudupakkam, Ryan Wagoner, Ved Patel, Katherine Santana, Arturo Alisio, Brian N Finck, Nicholas O Davidson, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3

Bullous Pemphigoid With Prominent Mucosal Involvement In The Setting Of Renal Allograft Rejection, Wesley T Hodges, Ahmed H Badawi, Ilana S Rosman, Amy C Musiek, Leonid Shmuylovich

2020-Current year OA Pubs

No abstract provided.

Show Me Ckdintercept Initiative: A Collective Impact Approach To Improve Population Health In Missouri, Katelyn Laue, Megan Schultz, Elizabeth Talbot-Montgomery, Alexandra Garrick, Anuja Java, Christine Corbett, Dana M Lammert, Joanna Rogers, Kathleen Davis, Kunal Malhotra, Marie Philipneri, Mary Ann Kimbel, Reem A Mustafa, Valerie Hardesty

2020-Current year OA Pubs

Ninety percent of people with chronic kidney disease (CKD) remain undiagnosed, most people at risk do not receive guideline-concordant testing, and disparities of care and outcomes exist across all stages of the disease. To improve CKD diagnosis and management across primary care, the National Kidney Foundation launched a collective impact (CI) initiative known as Show Me CKDintercept. The initiative was implemented in Missouri, USA from January 2021 to June 2022, using a data strategy, stakeholder engagement and relationship mapping, learning in action working groups (LAWG), and a virtual leadership summit. The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used …

Stabilizing The Proteomes Of Acute Myeloid Leukemia Cells: Implications For Cancer Proteomics, Robert W Sprung, Qiang Zhang, Michael H Kramer, Matthew C Christopher, Petra Erdmann-Gilmore, Yiling Mi, James P Malone, Timothy J Ley, R Reid Townsend

2020-Current year OA Pubs

Previous work has shown that inhibition of abundant myeloid azurophil granule-associated serine proteases (ELANE [neutrophil elastase], PRTN3 [protease 3], and CTSG [Cathepsin G]) is required to stabilize some proteins in myeloid cells. We therefore hypothesized that effective inhibition of these proteases may be necessary for quantitative proteomic analysis of samples containing myeloid cells. To test this hypothesis, we thawed viably preserved acute myeloid leukemia cells from cryovials in the presence or the absence of diisopropyl fluorophosphate (DFP), a cell-permeable and irreversible serine protease inhibitor. Global proteomic analysis was performed, using label-free and isobaric peptide-labeling quantitation. The presence of DFP resulted …

Lobe-Specific Lymph Node Sampling Is Associated With Lower Risk Of Cancer Recurrence, Melanie P Subramanian, Daniel B Eaton Jr, Brendan T Heiden, Whitney S Brandt, Ulysses L Labilles, Su-Hsin Chang, Yan Yan, Martin W Schoen, Mayank R Patel, Daniel Kreisel, Ruben G Nava, Theodore Thomas, Bryan F Meyers, Benjamin D Kozower, Varun Puri

2020-Current year OA Pubs

OBJECTIVE: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients.

METHODS: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data …

Spatial And Amplitude Dynamics Of Neurostimulation: Insights From The Acute Intrahippocampal Kainate Seizure Mouse Model, Thomas J Foutz, Nicholas Rensing, Lirong Han, Dominique M Durand, Michael Wong

2020-Current year OA Pubs

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

RESULTS: …

Screening For Problematic Opioid Use In The Emergency Department: Comparison Of Two Screening Measures, Brittany E Punches, Caroline E Freiermuth, Jon E Sprague, Jennifer L Brown, Elizabeth Hutzel-Dunham, Joshua Lambert, Robert Braun, Andrew Littlefield, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Michael V Pantalon, Rachel M Ancona, David F Kisor, Michael S Lyons

2020-Current year OA Pubs

STUDY OBJECTIVE: Earlier intervention for opioid use disorder (OUD) may reduce long-term health implications. Emergency departments (EDs) in the United States treat millions with OUD annually who may not seek care elsewhere. Our objectives were (1) to compare two screening measures for OUD characterization in the ED and (2) to determine the proportion of ED patients screening positive for OUD and those who endorse other substance use to guide future screening programs.

METHODS: A cross-sectional study of randomly selected adult patients presenting to three Midwestern US EDs were enrolled, with duplicate patients excluded. Surveys were administered via research assistant and …

Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.

2020-Current year OA Pubs

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …

A 3'Utr Insertion Is A Candidate Causal Variant At The Tmem106b Locus Associated With Increased Risk For Ftld-Tdp, Augustine Chemparathy, Chengran Yang, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Single-nucleotide variants near

METHODS: An exploratory analysis identified structural variants on neurodegeneration-related genes. Subsequent analyses focused on an

RESULTS: The primary analysis included 432 participants (52.5% female, age range 45-92 years). We identified a 316 bp

DISCUSSION: We identified a novel

Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton

2020-Current year OA Pubs

Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions …

Feasibility Of Interleukin-6 Receptor Blockade In Cardiac Antibody-Mediated Rejection, April A Pottebaum, Spenser E. January, Chang Liu, Steven Lavine, Joel D. Schilling, Kory J. Lavine

2020-Current year OA Pubs

BACKGROUND: Antibody-mediated rejection (AMR) remains a significant cause of heart transplant mortality with few effective therapies.

METHODS: This study aimed to describe initial experience of using interleukin-6 receptor blockade with tocilizumab in the treatment of acute cardiac AMR at Barnes-Jewish Hospital/Washington University Transplant Center from July 2017 to May 2021 (n = 7). Clinical, echocardiographic, and serum alloantibody data were analyzed before and after treatment.

RESULTS: All participants demonstrated marked improvement in functional status. Echocardiographic data following 4-6 mo of tocilizumab revealed significant improvements in biventricular systolic function for all participants. Consistent reductions in donor-specific HLA or angiotensin type I …

Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated …

Concurrent Administration Of Serotonergic Antidepressants And Ozanimod In Participants With Relapsing Multiple Sclerosis From The Open-Label Extension Daybreak Trial, Robert T Naismith, Jeffrey A Cohen, Amit Bar-Or, Giancarlo Comi, Krzysztof W Selmaj, Hans-Peter Hartung, James K Sheffield, Anthony Krakovich, Daniel Tatosian, Chun-Yen Cheng, Jennifer Reardon, Vadim Khaychuk, Jon V Riolo, Diego Silva, Bruce Ac Cree

2020-Current year OA Pubs

BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro.

OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717).

METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using …

Mousevuer: Video Based Open-Source System For Laboratory Mouse Home-Cage Monitoring, Ghadi Salem, Niall Cope, Marcial Garmendia, Alex Pu, Abhishek Somenhalli, Jonathan Krynitsky, Noah Cubert, Thomas Jones, George Dold, Anthony Fletcher, Alexxai Kravitz, Thomas Pohida, John Dennis

2020-Current year OA Pubs

Video monitoring of mice in the home-cage reveals behavior profiles without the disruptions caused by specialized test setups and makes it possible to quantify changes in behavior patterns continually over long time frames. Several commercial home-cage monitoring systems are available with varying costs and capabilities; however there are currently no open-source systems for home-cage monitoring. We present an open-source system for top-down video monitoring of research mice in a slightly modified home-cage. The system is designed for integration with Allentown NexGen ventilated racks and allows unobstructed view of up to three mice, but can also be operated outside the rack. …

Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs).

DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to …

Core Requirements Of Frailty Screening In The Emergency Department: An International Delphi Consensus Study, Elizabeth Moloney, Christopher R Carpenter, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study.

METHODS: A two-round electronic Delphi involving 37 participants from 10 countries was undertaken. Statements were generated from a prior systematic review examining frailty screening instruments in ED (logistic, psychometric and clinimetric properties). Reflexive thematic analysis generated a list of 56 statements …

High-Dimensional Quantile Mediation Analysis With Application To A Birth Cohort Study Of Mother-Newborn Pairs, Haixiang Zhang, Xiumei Hong, Yinan Zheng, Lifang Hou, Cheng Zheng, Xiaobin Wang, Lei Liu

2020-Current year OA Pubs

MOTIVATION: There has been substantial recent interest in developing methodology for high-dimensional mediation analysis. Yet, the majority of mediation statistical methods lean heavily on mean regression, which limits their ability to fully capture the complex mediating effects across the outcome distribution. To bridge this gap, we propose a novel approach for selecting and testing mediators throughout the full range of the outcome distribution spectrum.

RESULTS: The proposed high-dimensional quantile mediation model provides a comprehensive insight into how potential mediators impact outcomes via their mediation pathways. This method's efficacy is demonstrated through extensive simulations. The study presents a real-world data application …

Children's Neural Reactivity To Maternal Praise And Criticism: Associations With Early Depressive Symptoms And Maternal Depression, Matthew R J Vandermeer, Pan Liu, Ola Mohamed Ali, Andrew R Daoust, Marc F Joanisse, Deanna M Barch, Elizabeth P Hayden

2020-Current year OA Pubs

Caregiving experiences are implicated in children's depression risk; however, children's neural reactivity to positive and negative feedback from mothers, a potential mediator of depression risk, is poorly understood. In a sample of 81 children (

Legionella Pneumophila Usurps Host Cell Lipids For Vacuole Expansion And Bacterial Growth, Soma Ghosh, Saumya Bandyopadhyay, Danielle M. Smith, Sangeeta Adak, Clay F. Semenkovich, Laszlo Nagy, Michael J. Wolfgang, Tamara J. O'Connor

2020-Current year OA Pubs

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria …

Public Platform With 39,472 Exome Control Samples Enables Association Studies Without Genotype Sharing, Mykyta Artomov, Alexander A Loboda, Maxim N Artyomov, Mark J Daly

2020-Current year OA Pubs

Acquiring a sufficiently powered cohort of control samples matched to a case sample can be time-consuming or, in some cases, impossible. Accordingly, an ability to leverage genetic data from control samples that were already collected elsewhere could dramatically improve power in genetic association studies. Sharing of control samples can pose significant challenges, since most human genetic data are subject to strict sharing regulations. Here, using the properties of singular value decomposition and subsampling algorithm, we developed a method allowing selection of the best-matching controls in an external pool of samples compliant with personal data protection and eliminating the need for …

A Fluid Biomarker Reveals Loss Of Tdp-43 Splicing Repression In Presymptomatic Als-Ftd, Katherine E Irwin, Timothy Miller, Et Al.

2020-Current year OA Pubs

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs …

Longitudinal Predictors Of Health-Related Quality Of Life In Isolated Dystonia, Johanna Junker, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia.

METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year.

RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). …

Top 50 Most-Cited Studies About Osteochondritis Dissecans, Nicholas D Thomas, Raegan Mahler, Kylie Krombholz, Brendan Williams, Ted Ganley, Jeffrey J Nepple, Kevin Shea

2020-Current year OA Pubs

PURPOSE: To determine the 50 most frequently cited studies on osteochondritis dissecans (OCD) and to conduct a bibliometric analysis of these studies.

METHODS: We performed a search within the Clarivate Web of Science database, identifying articles published before December 2022 that encompass topics related to OCD. The search was conducted using the keywords "Osteochondritis Dissecans OR Osteochondritis OR Dissecans."Search results were then filtered using predetermined guidelines and criteria, and the 50 most-cited articles were selected for analysis. Extracted data included title, journal, design, main topic, joint, citations, year, country of origin, and level of evidence.

RESULTS: The search yielded 3,865 …

Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity And Inflammation In Myeloproliferative Neoplasms, Fan He, Angelo Ba Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel Ac Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, Layow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D'Alessandro, Jorge Di Paola, Stephen T. Oh

2020-Current year OA Pubs

Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and …

Circadian Immunity From Bench To Bedside: A Practical Guide, Huram Mok, Elaine Ostendorf, Alex Ganninger, Avi J. Adler, Guy Hazan, Jeffrey A. Haspel

2020-Current year OA Pubs

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, …

Current Understanding Of The Alzheimer's Disease-Associated Microbiome And Therapeutic Strategies, Dong-Oh Seo, David M Holtzman

2020-Current year OA Pubs

Alzheimer's disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of the disease is not completely clear. Recently, anti-Aβ antibodies have been shown to remove amyloid from the brain and slow the clinical progression of mild dementia by ~30%. However, exploring alternative strategies is crucial to understanding and developing more effective therapeutic interventions. In recent years, the microbiota-gut-brain axis has received significant attention in the AD field. Numerous studies have suggested that alterations in the gut microbiota composition are associated with the progression of AD, and several underlying mechanisms …

The Impact Of Patterns In Linkage Disequilibrium And Sequencing Quality On The Imprint Of Balancing Selection, Tristan J Hayeck, Yang Li, Timothy L Mosbruger, Jonathan P Bradfield, Adam G Gleason, George Damianos, Grace Tzun-Wen Shaw, Jamie L Duke, Laura K Conlin, Tychele N Turner, Marcelo A Fernández-Viña, Mahdi Sarmady, Dimitri S Monos

2020-Current year OA Pubs

Regions under balancing selection are characterized by dense polymorphisms and multiple persistent haplotypes, along with other sequence complexities. Successful identification of these patterns depends on both the statistical approach and the quality of sequencing. To address this challenge, at first, a new statistical method called LD-ABF was developed, employing efficient Bayesian techniques to effectively test for balancing selection. LD-ABF demonstrated the most robust detection of selection in a variety of simulation scenarios, compared against a range of existing tests/tools (Tajima's D, HKA, Dng, BetaScan, and BalLerMix). Furthermore, the impact of the quality of sequencing on detection of balancing selection was …