Medicine and Health Sciences Commons^™

Mitigating The Associations Of Kidney Dysfunction With Blood Biomarkers Of Alzheimer Disease By Using Phosphorylated Tau To Total Tau Ratios, Shorena Janelidze, Nicolas R Barthélemy, Yingxin He, Randall J Bateman, Oskar Hansson

2020-Current year OA Pubs

IMPORTANCE: Chronic kidney disease (CKD) has been associated with increased plasma concentrations of phosphorylated tau (p-tau) 217 and p-tau181, which potentially decreases their usefulness in the diagnostic workup of Alzheimer disease (AD).

OBJECTIVE: To investigate associations of CKD with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in AD.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients with mild cognitive impairment (cohort 1; enrollment in 2000-2005) and replication in cohort 2 from the Swedish BioFINDER-2 study, including both cognitively unimpaired individuals and those with cognitive impairment (enrollment in 2017-2022). All participants were from 2 memory clinics …

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 …

Multifactorial Profiling Of Epigenetic Landscapes At Single-Cell Resolution Using Multi-Tag, Michael P Meers, Geneva Llagas, Derek H Janssens, Christine A Codomo, Steven Henikoff

2020-Current year OA Pubs

Chromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare different chromatin-associated proteins in the same sample. Here we describe Multiple Target Identification by Tagmentation (MulTI-Tag), an antibody barcoding approach for profiling multiple chromatin features simultaneously in single cells. We optimized MulTI-Tag to retain high sensitivity and specificity, and we demonstrate detection of up to three histone modifications in the same cell: H3K27me3, H3K4me1/2 and H3K36me3. We apply MulTI-Tag to resolve distinct cell types and developmental trajectories; to distinguish unique, coordinated patterns of active and repressive …

The Natural History Of Curve Behavior After Brace Removal In Adolescent Idiopathic Scoliosis: A Literature Review, Scott Luhmann, Daphna Zaaroor-Regev, Vidyadhar V Upasani, Harry Shufflebarger

2020-Current year OA Pubs

PURPOSE: Brace treatment is the most common nonoperative treatment to prevent curve progression in adolescent idiopathic scoliosis (AIS). The goal of this review and analysis is to characterize curve behavior after completion of brace treatment and to identify factors that may facilitate the estimation of long-term curve progression.

METHOD: A review of the English language literature was completed using the MEDLINE (PUBMED) database of publications after 1990 until September 2020. Studies were included if they detailed a minimum of 1 year post-brace removal follow-up of AIS patients. Data retrieved from the articles included Cobb angle measurements of the major curves …

Mitos And King's Staging As Clinical Outcome Measures In Als: A Retrospective Analysis Of The Fortitude-Als Trial, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Adriano Chiò, Jinsy A Andrews, Angela Genge, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner

2020-Current year OA Pubs

OBJECTIVE: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS.

METHODS: This was a

RESULTS: The full analysis set consisted of 456 patients randomized 3:1 (

CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.

Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill

2020-Current year OA Pubs

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes …

Belimumab Versus Anifrolumab In Adults With Systemic Lupus Erythematosus: An Indirect Comparison Of Clinical Response At 52 Weeks, Binod Neupane, Pragya Shukla, Mahmoud Slim, Amber Martin, Michelle Petri, George K. Bertsias, Alfred H J Kim, Antonis Fanouriakis, Roger A. Levy, Deven Chauhan, Nick Ballew

2020-Current year OA Pubs

OBJECTIVE: To generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices.

METHODS: The SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated with an indirect treatment comparison. The evidence base consisted of randomised trials that were compiled through a systemic literature review.A feasibility assessment was performed to comprehensively compare the eligible trials and to determine the most appropriate indirect treatment comparison analysis method. A multilevel network meta-regression (ML-NMR) was implemented that adjusted for differences across trials in four baseline characteristics: SLE Disease Activity Index-2K, anti-double-stranded DNA antibody positive, low …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Grant V Bochicchio, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

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 …

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;

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 …

Metagenomic Analysis Of Dna Viruses With Targeted Sequence Capture Of Canine Lobular Orbital Adenomas And Normal Conjunctiva, Elizabeth A F Schaefer, Shirley Chu, Kristine M Wylie, Todd N Wylie, Obi L Griffith, Jacqueline W Pearce, Gayle C Johnson, Jeffrey N Bryan, Brian K Flesner

2020-Current year OA Pubs

Our study aims are: (1) to evaluate phenotypically normal canine conjunctival and orbital tissue and tissue from canine lobular orbital adenomas (CLOAs) for the presence of viral genomic material and (2) phylogenetically classify detected DNA viruses to determine if a DNA virus is associated with CLOAs. A total of 31 formalin fixed paraffin embedded CLOA tissue samples, 4 papillomas or sarcoid, and 10 fresh clinically normal conjunctival tissues were included in this study. Genomic DNA was isolated from all samples and sequencing libraries were prepared. The libraries were molecularly indexed and pooled and viral DNA was enriched via targeted sequence …

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

3d Printing Exposure And Perception In Radiology Residency: Survey Results Of Radiology Chief Residents, David Chen, Aravinda Ganapathy, Nihil Abraham, Kaitlin M Marquis, Grace L Bishop, Frank J Rybicki, Mark J Hoegger, David H Ballard

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: The purpose of this study is to summarize a survey of radiology chief residents focused on 3D printing in radiology.

MATERIALS AND METHODS: An online survey was distributed to chief residents in North American radiology residencies by subgroups of the Association of University Radiologists. The survey included a subset of questions focused on the clinical use of 3D printing and perceptions of the role of 3D printing and radiology. Respondents were asked to define the role of 3D printing at their institution and asked about the potential role of clinical 3D printing in radiology and radiology residencies. …

Eliciting Opinions On Health Messaging During The Covid-19 Pandemic: Qualitative Survey Study, Sienna Ruiz, Uzoma Charles Okere, Michelle Eggers, Catina O'Leary, Mary Politi, Fei Wan, Ashley J Housten

2020-Current year OA Pubs

BACKGROUND: Effective public health messaging has been necessary throughout the COVID-19 pandemic, but stakeholders have struggled to communicate critical information to the public, especially in different types of locations such as urban and rural areas.

OBJECTIVE: This study aimed to identify opportunities to improve COVID-19 messages for community distribution in rural and urban settings and to summarize the findings to inform future messaging.

METHODS: We purposively sampled by region (urban or rural) and participant type (general public or health care professional) to survey participants about their opinions on 4 COVID-19 health messages. We designed open-ended survey questions and analyzed the …

Cueing Natural Event Boundaries Improves Memory In People With Post-Traumatic Stress Disorder, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks

2020-Current year OA Pubs

People with post-traumatic stress disorder (PTSD) often report difficulty remembering information in their everyday lives. Recent findings suggest that such difficulties may be due to PTSD-related deficits in parsing ongoing activity into discrete events, a process called event segmentation. Here, we investigated the causal relationship between event segmentation and memory by cueing event boundaries and evaluating its effect on subsequent memory in people with PTSD. People with PTSD (n = 38) and trauma-matched controls (n = 36) watched and remembered videos of everyday activities that were either unedited, contained visual and auditory cues at event boundaries, or contained visual and …

Large Multi-Ethnic Genetic Analyses Of Amyloid Imaging Identify New Genes For Alzheimer Disease, Muhammad Ali, Priyanka Gorijala, Daniel Western, Jigyasha Timsina, Maria V Fernández, Gengsheng Chen, Brian Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Eric Mcdade, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10

Inulin Diet Uncovers Complex Diet-Microbiota-Immune Cell Interactions Remodeling The Gut Epithelium, Renan Oliveira Corrêa, José Luís Fachi, Marco Colonna, Et Al.

2020-Current year OA Pubs

BACKGROUND: The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts …

Activation Of The Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated By Plasmepsin X Destruction Of The Prodomain, Sumit Mukherjee, Armiyaw S. Nasamu, Kelly C. Rubiano, Daniel E. Goldberg

2020-Current year OA Pubs

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated …

Molnupiravir And Risk Of Post-Acute Sequelae Of Covid-19: Cohort Study, Yan Xie, Taeyoung Choi, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVE: To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.

DESIGN: Cohort study.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or …

Mrgpra3-Expressing Pruriceptors Drive Pruritogen-Induced Alloknesis Through Mechanosensitive Piezo2 Channel, Ping Lu, Yonghui Zhao, Zili Xie, Huan Zhou, Xinzhong Dong, Gregory F Wu, Brian S Kim, Jing Feng, Hongzhen Hu

2020-Current year OA Pubs

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, …

Nk Cell-Derived Extracellular Granzyme B Drives Epithelial Ulceration During Hsv-2 Genital Infection, Ying Shiang Lim, Aisha G Lee, Xiaoping Jiang, Jason M Scott, Adjoa Cofie, Sandeep Kumar, Dania Kennedy, David J Granville, Haina Shin

2020-Current year OA Pubs

Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model of vaginal herpes simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation of the serine protease granzyme B in the vagina, coinciding with vaginal epithelial ulceration. Genetic loss of granzyme B or therapeutic inhibition by a specific protease inhibitor reduces disease and restores epithelial integrity without altering viral control. Distinct effects of granzyme B and perforin deficiency on pathology indicates that granzyme B acts independent of its classic …

Site-1 Protease Inhibits Mitochondrial Respiration By Controlling The Tgf-Β Target Gene Mss51, Muhammad G Mousa, Lahari Vuppaladhadiam, Meredith O Kelly, Terri Pietka, Shelby Ek, Karen C Shen, Gretchen A Meyer, Brian N Finck, Rita T Brookheart

2020-Current year OA Pubs

The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P …

Transcriptomic Atlas And Interaction Networks Of Brain Cells In Mouse Cns Demyelination And Remyelination, Jinchao Hou, Yingyue Zhou, Zhangying Cai, Marina Terekhova, Amanda Swain, Prabhakar S Andhey, Rafaela M Guimaraes, Alina Ulezko Antonova, Tian Qiu, Sanja Sviben, Gregory Strout, James A J Fitzpatrick, Yun Chen, Susan Gilfillan, Do-Hyun Kim, Steven J Van Dyken, Maxim N Artyomov, Marco Colonna

2020-Current year OA Pubs

Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFB

Valoctocogene Roxaparvovec Gene Transfer In Participants With Hiv, Margaret V Ragni, Elaine Majerus, Sylvia Fong, Bridget Yates, Stephen Scheeler, Lisa Razon, Hua Yu, Divya B Reddy, Tara M Robinson

2020-Current year OA Pubs

No abstract provided.

Microfluidic Device Facilitates In Vitro Modeling Of Human Neonatal Necrotizing Enterocolitis-On-A-Chip, Wyatt E. Lanik, Cliff J. Luke, Lila S. Nolan, Qingqing Gong, Lauren C. Frazer, Jamie M. Rimer, Sarah E. Gale, Raymond Luc, Shay S. Bidani, Carrie A. Sibbald, Angela N. Lewis, Belgacem Mihi, Pranjal Agrawal, Martin Goree, Marlie Maestas, Elise Hu, David F. Peters, Misty Good

2020-Current year OA Pubs

Necrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants that is associated with an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. We describe an in vitro model of the human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology. This model utilizes intestinal enteroids grown from surgically harvested intestinal tissue from premature infants and cocultured with human intestinal microvascular endothelial cells within a microfluidic device. We used our Neonatal-Intestine-on-a-Chip to recapitulate NEC pathophysiology by adding infant-derived microbiota. This model, named NEC-on-a-Chip, simulates the predominant features of …