Medicine and Health Sciences Commons^™

Assessment Of The Dissemination Of Covid-19-Related Articles Across Social Media: Altmetrics Study, Haley Tornberg, Carine Moezinia, Chapman Wei, Simone A Bernstein, Chaplin Wei, Refka Al-Beyati, Theodore Quan, David J Diemert

2020-Current year OA Pubs

BACKGROUND: The use of social media assists in the distribution of information about COVID-19 to the general public and health professionals. Alternative-level metrics (ie, Altmetrics) is an alternative method to traditional bibliometrics that assess the extent of dissemination of a scientific article on social media platforms.

OBJECTIVE: Our study objective was to characterize and compare traditional bibliometrics (citation count) with newer metrics (Altmetric Attention Score [AAS]) of the top 100 Altmetric-scored articles on COVID-19.

METHODS: The top 100 articles with the highest AAS were identified using the Altmetric explorer in May 2020. AAS, journal name, and mentions from various social …

Effects Of Nalcn-Encoded Na+ Leak Currents On The Repetitive Firing Properties Of Scn Neurons Depend On K+-Driven Rhythmic Changes In Input Resistance, Nien-Du Yang, Rebecca L Mellor, Tracey O Hermanstyne, Jeanne M Nerbonne

2020-Current year OA Pubs

Neurons in the suprachiasmatic nucleus (SCN) generate circadian changes in the rates of spontaneous action potential firing that regulate and synchronize daily rhythms in physiology and behavior. Considerable evidence suggests that daily rhythms in the repetitive firing rates (higher during the day than at night) of SCN neurons are mediated by changes in subthreshold potassium (K

A Multicenter Analysis Of The Outcomes With Venetoclax In Patients With Relapsed Mantle Cell Lymphoma, Yazeed Sawalha, Scott Goldsmith, Brad S Kahl, Et Al.

2020-Current year OA Pubs

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n = 50, 62%) or in combination with a Bruton tyrosine kinase inhibitor (BTKi) (n = 16, 20%), an anti-CD20 monoclonal antibody (n = 11, 14%), or other active agents at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTKis in 91%. Venetoclax alone or in combination resulted in an overall response rate …

Building Capacity Of Community Nurses To Strengthen The Management Of Uncomplicated Hypertension In Persons Living With Hiv In Low- And Middle-Income Countries, Dike Ojji, Daphne Lew, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Poor training of non-physician healthcare workers (especially community nurses) could hinder the successful integration of cardiovascular disease (CVD) management into HIV chronic care in primary healthcare facilities in low- and middle-income countries. To address this limitation, we included a holistic training programme with a robust module for both practice facilitators and community nurses as part of the formative stages of the managing hypertension among people living with HIV: an integrated model (MAP-IT), which is a study that is evaluating the effectiveness of practice facilitation on the integration of a task-strengthening strategy for hypertension control (TASSH) into primary healthcare centres …

A Single F153sβ3 Mutation Causes Constitutive Integrin Αiibβ3 Activation In A Variant Form Of Glanzmann Thrombasthenia, Sevasti B Koukouritaki, Aye Myat M Thinn, Katrina J Ashworth, Juan Fang, Haley S Slater, Lily M Du, Huong Thi Thu Nguyen, Xavier Pillois, Alan T Nurden, Christopher J Ng, Jorge Di Paola, Jieqing Zhu, David A Wilcox

2020-Current year OA Pubs

This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild bleeding in a physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists of activation, although microfluidic analysis with whole blood displays moderate ex vivo platelet adhesion and aggregation consistent with mild bleeding. Immunocytometry shows reduced expression of αIIbβ3 on quiescent platelets that spontaneously bind/store fibrinogen, and activation-dependent antibodies (ligand-induced binding site-319.4 and PAC-1) report β3 extension suggesting an intrinsic activation phenotype. Genetic analysis reveals a single F153Sβ3 substitution within the βI-domain from a heterozygous T556C nucleotide substitution of ITGB3 exon …

A Global Study For Acute Myeloid Leukemia With Rarg Rearrangement, Hong-Hu Zhu, John S Welch, Et Al.

2020-Current year OA Pubs

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and …

Real-Time Environmental Surveillance Of Sars-Cov-2 Aerosols, Joseph V Puthussery, Kevin R Mcbrearty, Brookelyn M Doherty, Woodrow D Gardiner, Jordan P Magrecki, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Et Al.

2020-Current year OA Pubs

Real-time surveillance of airborne SARS-CoV-2 virus is a technological gap that has eluded the scientific community since the beginning of the COVID-19 pandemic. Offline air sampling techniques for SARS-CoV-2 detection suffer from longer turnaround times and require skilled labor. Here, we present a proof-of-concept pathogen Air Quality (pAQ) monitor for real-time (5 min time resolution) direct detection of SARS-CoV-2 aerosols. The system synergistically integrates a high flow (~1000 lpm) wet cyclone air sampler and a nanobody-based ultrasensitive micro-immunoelectrode biosensor. The wet cyclone showed comparable or better virus sampling performance than commercially available samplers. Laboratory experiments demonstrate a device sensitivity of …

Thermosensitive And Antioxidant Wound Dressings Capable Of Adaptively Regulating Tgfβ Pathways Promote Diabetic Wound Healing, Hong Niu, Ya Guan, Ting Zhong, Liang Ma, Mohamed Zayed, Jianjun Guan

2020-Current year OA Pubs

Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with …

Proteome Wide Association Studies Of Lrrk2 Variants Identify Novel Causal And Druggable Proteins For Parkinson's Disease, Bridget Phillips, Daniel Western, Lihua Wang, Jigyasha Timsina, Yichen Sun, Priyanka Gorijala, Chengran Yang, Anh Do, Niko-Petteri Nykänen, John C Morris, Suzanne E Schindler, Anne M Fagan, Joel S Perlmutter, Laura Ibanez, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Common and rare variants in the LRRK2 locus are associated with Parkinson's disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of …

Proportion Of Physicians Who Treat Patients With Greater Social And Clinical Risk And Physician Inclusion In Medicare Advantage Networks, Jung Ho Gong, Kenton J Johnston, David J Meyers

2020-Current year OA Pubs

IMPORTANCE: Medicare Advantage (MA) plans are expanding rapidly, now serving 50% of all Medicare enrollees. Little is known about how inclusion rates of physicians in MA plan networks vary by the social and clinical risks of their patients.

OBJECTIVE: To examine the association of physicians caring for patients with higher levels of social and clinical risk in traditional Medicare (TM) with the likelihood of inclusion in MA plan networks.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated the number of patients of physicians participating in TM Part B in 2019. The data analysis was conducted between June 2022 and March …

Cardiovascular Toxicities After Anthracycline And Vegf-Targeted Therapies In Adolescent And Young Adult Cancer Survivors, Jeannette R Wong-Siegel, Robert J Hayashi, Randi Foraker, Joshua D Mitchell

2020-Current year OA Pubs

BACKGROUND: Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood.

OBJECTIVE: This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy.

METHODS: Data were extracted from electronic medical records over a fourteen-year period at a single institution. …

Endothelial Cell Cd36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Transfer And Circulating Fatty Acid Levels, V S Peche, T A Pietka, M Jacome-Sosa, D Samovski, H Palacios, G Chatterjee-Basu, A C Dudley, W Beatty, G A Meyer, I J Goldberg, N A Abumrad

2020-Current year OA Pubs

Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80-100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking …

High Dynamic Range 3d Motion Tracking Using Circular Scans With Optical Coherence Tomography, Senyue Hao, Marcello Magri Amaral, Chao Zhou

2020-Current year OA Pubs

Motion artifacts, from such sources as heartbeats, respiration, or peristalsis, often degrade microscopic images or videos of live subjects. We have developed a method using circular optical coherence tomography (OCT) scans to track the transverse and axial motion of biological samples at speeds ranging from several micrometers per second to several centimeters per second. We achieve fast and high-precision measurements of the magnitude and direction of the sample's motion by adaptively controlling the circular scan pattern settings and applying interframe and intraframe analyses. These measurements are the basis of active motion compensation via feedback control for future

Unexpected Sound Omissions Are Signaled In Human Posterior Superior Temporal Gyrus: An Intracranial Study, Hohyun Cho, Yvonne M Fonken, Markus Adamek, Richard Jimenez, Jack J Lin, Gerwin Schalk, Robert T Knight, Peter Brunner

2020-Current year OA Pubs

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes …

An Immunostimulatory Glycolipid That Blocks Sars-Cov-2, Rsv, And Influenza Infections In Vivo, Moriya Tsuji, Zhenlu Chong, Tamarand L Darling, Kuljeet Seehra, Adrianus C M Boon, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as …

Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality In People With Human Immunodeficiency Virus In High-Income Countries: An International Collaborative Cohort Study, Suzanne M Ingle, Elvin Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings.

METHODS: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 …

Comparison Of Patient Exit Interviews With Unannounced Standardised Patients For Assessing Hiv Service Delivery In Zambia: A Study Nested Within A Cluster Randomised Trial, Kombatende Sikombe, Aaloke Mody, Ingrid Eshun-Wilson, Elvin Geng, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias.

SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART).

PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021.

INTERVENTION: Systematic sample (every n

OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to …

Rad51 Foci As A Biomarker Predictive Of Platinum Chemotherapy Response In Ovarian Cancer, Amanda J Compadre, Lillian N Van Biljon, Mark C Valentine, Emily Graham, Bisiayo Fashemi, Emilee N Kotnik, Isaac Cooper, Lindsay M Kuroki, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, David G Mutch, Matthew A Powell, Lulu Sun, Nima Mosammaparast, Peinan Zhao, Elena Lomonosova, Dineo Khabele, Mary M Mullen, Et Al.

2020-Current year OA Pubs

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell …

Two Neuroanatomical Signatures In Schizophrenia: Expression Strengths Over The First 2 Years Of Treatment And Their Relationships To Neurodevelopmental Compromise And Antipsychotic Treatment, Stefan Du Plessis, Ganesh B Chand, Guray Erus, Lebogang Phahladira, Hilmar K Luckhoff, Retha Smit, Laila Asmal, Daniel H Wolf, Christos Davatzikos, Robin Emsley

2020-Current year OA Pubs

BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively.

STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 …

Human Gut Bacteria Tailor Extracellular Vesicle Cargo For The Breakdown Of Diet- And Host-Derived Glycans, Mariana G Sartorio, Evan J Pardue, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Extracellular vesicles are produced in all three domains of life, and their biogenesis has common ancient origins in eukaryotes and archaea. Although bacterial vesicles were discovered several decades ago and multiple roles have been attributed to them, no mechanism has been established for vesicles biogenesis in bacteria. For this reason, there is a significant level of skepticism about the biological relevance of bacterial vesicles.

Aerobic Exercise Reverses Aging-Induced Depth-Dependent Decline In Cerebral Microcirculation, Paul Shin, Ikbal Şencan-Eğilmez, Et Al.

2020-Current year OA Pubs

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white …

Metabolic Signatures Of Cardiac Dysfunction, Multimorbidity, And Post-Transcatheter Aortic Valve Implantation Death, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort …

Adherence To Healthy Diet And Risk Of Cardiovascular Disease In Adult Survivors Of Childhood Cancer In The St. Jude Lifetime Cohort: A Cross-Sectional Study, Tuo Lan, Mei Wang, Matthew J Ehrhardt, Shu Jiang, Jennifer Q Lanctot, Gregory T Armstrong, Melissa M Hudson, Graham A Colditz, Leslie L Robison, Yikyung Park

2020-Current year OA Pubs

BACKGROUND: Whether diet has beneficial effects on cardiovascular disease (CVD) in childhood cancer survivors as in the general population is unknown. Therefore, we examined associations between dietary patterns and risk of CVD in adult survivors of childhood cancer.

METHODS: Childhood cancer survivors, 18-65 years old in the St Jude Lifetime Cohort (1882 men and 1634 women) were included in the analysis. Dietary patterns were defined by the adherence to the Healthy Eating Index (HEI)-2015, Dietary Approaches to Stop Hypertension (DASH), and alternate Mediterranean diet (aMED) based on a food frequency questionnaire at study entry. CVD cases (323 in men and …

T-Bet And Eomes Sustain Mature Human Nk Cell Identity And Antitumor Function, Pamela Wong, Jennifer A. Foltz, Lily Chang, Carly C. Neal, Tony Yao, Celia C. Cubitt, Jennifer Tran, Samantha Kersting-Schadek, Sathvik Palakurty, Natalia Jaeger, David A. Russler-Germain, Nancy D. Marin, Margery Gang, Julia A. Wagner, Alice Y. Zhou, Miriam T. Jacobs, Mark Foster, Timothy Schappe, Lynne Marsala, Ethan Mcclain, Patrick Pence, Michelle Becker-Hapak, Bryan Fisk, Allegra A. Petti, Obi L. Griffith, Malachi Griffith, Melissa M. Berrien-Elliott, Todd A. Fehniger

2020-Current year OA Pubs

Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which …

Assessment Of Gastroesophageal Reflux Symptoms And Sleep Quality Among Women In The Nurses' Health Study Ii, Jane Ha, Raaj S Mehta, Yin Cao, Tianyi Huang, Kyle Staller, Andrew T Chan

2020-Current year OA Pubs

IMPORTANCE: Limited data exist on the association of gastroesophageal reflux (GER) symptoms with sleep quality.

OBJECTIVE: To prospectively investigate the association between GER symptoms and sleep quality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data from the Nurses' Health Study II of female nurses in the US. Participants self-reported the frequency and duration of GER symptoms beginning June 2005, with updates every 4 years through June 2015. Follow-up was completed June 2019, and data were analyzed from November 15, 2022, to June 4, 2023.

EXPOSURES: Frequency and duration of GER symptoms.

MAIN OUTCOMES AND MEASURES: Poor sleep quality …

Comparison Of Electronic Health Record Messages To Mental Health Care Professionals Before Vs After Covid-19 Pandemic, Simone A Bernstein, Alison L Huckenpahler, Ginger E Nicol, Jessica A Gold

2020-Current year OA Pubs

No abstract provided.

Genetic Characterization Of Primary And Metastatic High-Grade Serous Ovarian Cancer Tumors Reveals Distinct Features Associated With Survival, Emilee N Kotnik, Mary M Mullen, Nicholas C Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S Hagemann, Carolyn K Mccourt, Premal H Thaker, Andrea R Hagemann, Matthew A Powell, David G Mutch, Dineo Khabele, Gregory D Longmore, Christopher A Maher, Christopher A Miller, Katherine C Fuh, Et Al.

2020-Current year OA Pubs

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene …

Age-Related Alterations In Meningeal Immunity Drive Impaired Cns Lymphatic Drainage, Justin Rustenhoven, Georgios Pavlou, Steffen E Storck, Taitea Dykstra, Siling Du, Zhengpeng Wan, Daniel Quintero, Joshua P Scallan, Igor Smirnov, Roger D Kamm, Jonathan Kipnis

2020-Current year OA Pubs

The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer's disease, impaired meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins in the CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, the mechanisms underlying this decline remain elusive. Here, we demonstrate that age-related alterations in meningeal immunity underlie this lymphatic impairment. Single-cell RNA sequencing of meningeal lymphatic endothelial cells from aged mice revealed their response to IFNγ, which was increased in the aged meninges due to …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

A Rapid Cell-Free Expression And Screening Platform For Antibody Discovery, Andrew C Hunt, Bastian Vögeli, Ahmed O Hassan, Laura Guerrero, Weston Kightlinger, Danielle J Yoesep, Antje Krüger, Madison Dewinter, Michael S Diamond, Ashty S Karim, Michael C Jewett

2020-Current year OA Pubs

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike …