158 Works

Data from: Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA

Richard B. Lanman, Stefanie A. Mortimer, Oliver A. Zill, Dragan Sebisanovic, Rene B. Lopez, Sibel Blau, Eric A. Collisson, Stephen G. Drivers, Dave S. B. Hoon, E. Scott Kopetz, Jeeyun Lee, Petros George Nikolinakos, Bahram G. Kermani, Helmy Eltoukhy & AmirAli Talasaz
Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood...

Data from: The relationship between risk of bias criteria, research outcomes, and study sponsorship in a cohort of preclinical thiazolidinedione animal studies: a meta-analysis

Maher Abdel-Sattar, David Krauth, Andrew Anglemyer & Lisa Bero
Introduction: There is little evidence regarding the influence of conflicts of interest on preclinical research. This study examines whether industry sponsorship is associated with increased risks of bias and/or effect sizes of outcomes in published preclinical thiazolidinedione (TZD) studies. Methods: We identified preclinical TZD studies published between January 1, 1965, and November 14, 2012. Coders independently extracted information on study design criteria aimed at reducing bias, results for all relevant outcomes, sponsorship source and investigator...

Data from: Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers

Ruijun Chen, Nihar R. Desai, Joseph S. Ross, Weiwei Zhang, Katherine H. Chau, Brian Wayda, Karthik Murugiah, Daniel Y. Lu, Amit Mittal & Harlan M. Krumholz
Objective: To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. Design: Cross sectional analysis. Setting: Academic medical centers in the United States. Participants: Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. Methods: Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on...

Data from: Temporal structure of human gaze dynamics is invariant during free viewing

Colleen A. Marlow, Indre V. Viskontas, Alisa Matlin, Cooper Boydston, Adam Boxer & Richard P. Taylor
We investigate the dynamic structure of human gaze and present an experimental study of the frequency components of the change in gaze position over time during free viewing of computer-generated fractal images. We show that changes in gaze position are scale-invariant in time with statistical properties that are characteristic of a random walk process. We quantify and track changes in the temporal structure using a well-defined scaling parameter called the Hurst exponent, H. We find...

Aberrant oligodendroglial-vascular interactions disrupt the Blood Brain Barrier triggering CNS inflammation

Jianqin Niu, Kicheol Kim, Stephen Fancy & Sergio Baranzini
Disruption of the blood brain barrier (BBB) is critical to initiation and perpetuation of disease in Multiple Sclerosis (MS). We report here an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent remyelination. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in active MS lesions, representing an inability to properly detach from vessels following perivascular migration. These perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte...

Experiences of women who travel for abortion: a mixed methods systematic review

Jill Barr-Walker, Ruvani Jayaweera, Ana Ramirez & Caitlin Gerdts
Objective To systematically review the literature on women’s experiences traveling for abortion and assess how this concept has been explored and operationalized, with a focus on travel distance, cost, delays, and other barriers to receiving services. Background Increasing limitations on abortion providers and access to care have increased the necessity of travel for abortion services around the world. No systematic examination of women’s experiences traveling for abortion has been conducted; this mixed-methods review provides a...

Coping with impostor feelings: evidence-based recommendations from a mixed methods study

Jill Barr-Walker, Debra A. Werner, Liz Kellermeyer & Michelle B. Bass
The negative effects of impostor phenomenon, also called impostor syndrome, include burnout and decreased job satisfaction and have led to an increased interest in addressing this issue in libraries in recent years. While previous research has shown that many librarians experience impostor phenomenon, the experience of coping with these feelings has not been widely studied. Our study’s aim was to understand how health sciences librarians cope with impostor phenomenon in the workplace, using a quantitative...

Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene PogZ

Margaret Cunniff & Vikaas Sohal
Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for Pogz, a high confidence autism gene. Pogz+/- mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex...

Data from: Testing models of reciprocal relations between social influence and integration in STEM across the college years

Paul Hernandez, V. Bede Agocha, Lauren Carney, Mica Estrada, Sharon Lee, David Loomis, Michelle Williams & Crystal Park
The present study tests predictions from the Tripartite Integration Model of Social Influences (TIMSI) concerning processes linking social interactions to social integration into science, technology, engineering, and mathematics (STEM) communities and careers. Students from historically overrepresented groups in STEM were followed from their senior year of high school through their senior year in college. Based on TIMSI, we hypothesized that interactions with social influence agents (operationalized as mentor network diversity, faculty mentor support, and research...

Prolonged and coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during convalescence

Nadia Roan
CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but to what extent these cells coordinate with other adaptive immune processes and change during convalescence is not clear. We screened 21 well-characterized convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, to identify one participant with an immunodominant response against Nuc322-331, a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. By conducting...

Anatomy, ontogeny, and evolution of the archosaurian respiratory system: a case study on Alligator mississippiensis and Struthio camelus

Emma Schachner, Brandon Hedrick, Heather Richbourg, John Hutchinson & CG Farmer
The avian lung is highly specialized and is both functionally and morphologically distinct from that of their closest extant relatives, the crocodilians. It is highly partitioned, with a unidirectionally ventilated and immobilized gas-exchanging lung, and fully decoupled, compliant, poorly vascularized ventilatory air-sacs. To understand the evolutionary history of the archosaurian (birds, crocodilians and their common ancestors) respiratory system, it is essential to determine which anatomical characteristics are shared between birds and crocodilians and the role...

Data from: Distinct association between APOE ε2 and Aβ in Alzheimer- and vascular-type cognitive impairment

Jin San Lee, Hyejoo Lee, Seongbeom Park, Yeongsim Choe, Yu Hyun Park, Bo Kyoung Cheon, Alice Hahn, Rik Ossenkoppele, Hee Jin Kim, Seonwoo Kim, Heejin Yoo, Hyemin Jang, Soo Hyun Cho, Seung Joo Kim, Jun Pyo Kim, Young Hee Jung, Key-Chung Park, Charles DeCarli, Michael Weiner, Duk L. Na & Sang Won Seo
Objective: To investigate the association between apolipoprotein E (APOE) genotype and amyloid-β (Aβ) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer’s disease-related cognitive impairment (ADCI). Methods: This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on Aβ-positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were...

CRISPR-Cas system of a prevalent human gut bacterium reveals hyper-targeting against phages in a human virome catalog

Jordan E. Bisanz, Paola Soto-Perez, Joel D. Berry, Kathy N. Lam, Joseph Bondy-Denomy & Peter J. Turnbaugh
Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a...

Prevalence of elevated liver transaminases and their relationship with alcohol use in people living with HIV on anti-retroviral therapy in Uganda

Judith Hahn
Background: Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude “regular and heavy alcohol drinkers” from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. Setting: The Immune Suppression Syndrome Clinic of Mbarara, Uganda. Methods: We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine...

DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation

Xiao Huang, Jasper Z. Williams, Ryan Chang, Zhongbo Li, Cassandra E. Burnett, Rogelio Hernandez-Lopez, Initha Setiady, Eric Gai, David M. Patterson, Wei Yu, Kole T. Roybal, Wendell A. Lim & Tejal A. Desai
Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micron-sized ICEp were injected intratumorally to present a priming signal for systemically administered...

The onset and offset of noxious stimuli robustly modulate perceived pain intensity

Irina Strigo, Benedict Alter & Howard Fields
Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase...

Hemotological and morphometric measurements from geladas

Kenneth L. Chiou, Mareike C. Janiak, India A. Schneider-Crease, Sharmi Sen, Ferehiwot Ayele, Idrissa S. Chuma, Sascha Knauf, Alemayehu Lemma, Anthony V. Signore, Anthony M. D’Ippolito, Belayneh Abebe, Abebaw Azanaw Haile, Fanuel Kebede, Peter J. Fashing, Nga Nguyen, Colleen McCann, Marlys L. Houck, Jeffrey D. Wall, Andrew S. Burrell, Christina M. Bergey, Jeffrey Rogers, Jane E. Phillips-Conroy, Clifford J. Jolly, Amanda D. Melin, Jay F. Storz … & Noah Snyder-Mackler
Primates have adapted to numerous environments and lifestyles but very few species are native to high elevations. Here, we investigated high-altitude adaptations in the gelada (Theropithecus gelada), a monkey endemic to the Ethiopian Plateau. We examined genome-wide variation in conjunction with measurements of haematological and morphological traits. Our new gelada reference genome is highly intact and assembled at chromosome-length levels. Unexpectedly, we identified a chromosomal polymorphism in geladas that could potentially contribute to reproductive barriers...

Raw microscopy data from: Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Vladislav Belyy, Iratxe Zuazo-Gaztelu, Andrew Alamban, Avi Ashkenazi & Peter Walter
Protein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER membrane-resident kinase/RNase that mediates signal transmission in the most evolutionarily conserved branch of the UPR. Dimerization and/or higher-order oligomerization of IRE1 are thought to be important for its activation mechanism, yet the actual oligomeric states of inactive, active, and attenuated mammalian IRE1 complexes remained unknown. We developed an...

Comparable impairment of vascular endothelial function by a wide range of electronic nicotine delivery devices

Poonam Rao
Introduction Electronic nicotine delivery systems (ENDS; i.e., vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, their cardiovascular effects are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices, including a new ultrasonic vaping device, impairs endothelial function. Methods We measured arterial flow-mediated dilation (FMD) in rats (n=8/group) exposed to single session of 10 cycles...

Multiplex IgG antibody response and malaria parasitemia among children ages 1-59 months in the MORDOR Niger trial, 2015-2018

Benjamin Arnold, Ahmed Arzika, Ramatou Maliki, E. Brook Goodhew, Eric Rogier, Jeffrey Priest, Jeremy Keenan, Thomas Lietman & Diana Martin
We measured IgG responses to several malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural, MORDOR Niger placebo-controlled trial over a three-year period (n=5,642 blood specimens, n=3,814 children ages 1-59 months). We compared seroprevalence and serological force of infection between 15 communities that received biannual mass distribution of azithromycin versus placebo. The study included antigens to: Plasmodium falciparum (MSP-1, AMA1, GLURP-Ro, LSA1, CSP, HRP2), P....

Persistence of ambigrammatic narnaviruses requires translation of the reverse open reading frame

Hanna Retallack, Katerina Popova, Matthew Laurie, Sara Sunshine & Joseph DeRisi
Narnaviruses are RNA viruses detected in diverse fungi, plants, protists, arthropods and nematodes. Though initially described as simple single-gene non-segmented viruses encoding RNA-dependent RNA polymerase (RdRp), a subset of narnaviruses referred to as “ambigrammatic” harbor a unique genomic configuration consisting of overlapping open reading frames (ORFs) encoded on opposite strands. Phylogenetic analysis supports selection to maintain this unusual genome organization, but functional investigations are lacking. Here, we establish the mosquito-infecting Culex narnavirus 1 (CxNV1) as...

Effect of six- versus eight-month regimen on treatment success and smear conversion among retreatment patients

Jonathan Izudi, Lila Sheira, Francis Bajunirwe, Sandra McCoy & Adithya Cattamanchi
Background: In 2017, the regimen for patients with retreatment tuberculosis (TB) changed from an eight-month treatment regimen that consisted of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, and Streptomycin (2RHZES/1RHZE/5RHE) to a six-month treatment regimen (2RHZE/4RH). Currently, there is uncertainty regarding the effect of the six-month treatment regimen on treatment outcomes across TB Control Programs. We evaluated the effect of the six-month treatment regimen on treatment success rate (TSR) and sputum smear conversion (SSC) among patients with retreatment...

PhIP-Seq/VirScan Coronavirus phage display assay in maternal-infant dyads

Mary Prahl
We investigated antibody linear epitope binding and transplacental transfer using the PhIP-seq/VirScan SARS-CoV-2 Spike protein phage display array in mother-infant dyads at the time of birth. SARS-CoV-2 antibody linear epitope binding after vaccination during pregnancy showed high levels of binding in carboxy terminal of N-terminal, S1/S2 cleavage site, and S2 — with multiple immunodominant regions found in the majority of mothers and infants.

Data from: Characteristics and outcomes of women utilizing emergency medical services for third-trimester pregnancy-related complaints in India: a prospective observational study

Matthew C. Strehlow, Jennifer A. Newberry, Corey B. Bills, Hyeyoun Min, Ann E. Evensen, Lawrence Leeman, Elizabeth A. Pirrotta, G. V. Ramana Rao & S. V. Mahadevan
Objectives: Characterize the demographics, management, and outcomes of obstetric patients transported by emergency medical services (EMS). Design: Prospective observational study. Setting: Five Indian states utilizing a centralized EMS agency that transported 3.1 million pregnant women in 2014. Participants: This study enrolled a convenience sample of 1684 women in third trimester of pregnancy calling with a “pregnancy-related” complaint for free-of-charge ambulance transport. Calls were deemed “pregnancy-related” if categorized by EMS dispatchers as “pregnancy”, “childbirth”, “miscarriage”, or...

Data from: Accuracy of popular media reporting on tobacco cessation therapy in substance abuse and mental health populations

David Krauth & Dorothy Apollonio
Background: Tobacco cessation therapy is not consistently provided for alcohol, drug abuse and mental health (ADM) populations, despite the enormous health consequences of tobacco addiction in these groups and research supporting the effectiveness of treatment. Policymakers, however, tend to rely on popular media reports rather than the scientific literature in regulating treatment. Our goal was to determine whether popular reporting accurately reflects findings from the scientific literature on tobacco cessation treatment for ADM populations in...

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