bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pervasive Discrimination and Allostatic Load in African American and White Adults
Authors: Van Dyke Miriam E. , Baumhofer Nicole Kau’i , Slopen Natalie , Mujahid Mahasin S. , Clark Cheryl R. , Williams David R. , Lewis Tené T. 
Published: February 2020

ABSTRACT

Objective
This study aimed to examine associations among race, the accumulation of multiple forms of discriminatory experiences (i.e., “pervasive discrimination”), and allostatic load (AL) in African Americans and whites in midlife.

Methods
Using data collected in 2004 to 2006 from 226 African American and 978 white adults (57% female; mean [SD] age = 54.7 [0.11] years) in the Midlife in the United States II Biomarker Project, a pervasive discrimination score was created by combining three discrimination scales, and an AL score was created based on 24 biomarkers representing seven physiological systems. Linear regression models were conducted to examine the association between pervasive discrimination and AL, adjusting for demographics and medical, behavioral, and personality covariates. A race by pervasive discrimination interaction was also examined to determine whether associations varied by race.

Results
African Americans had higher pervasive discrimination and AL scores than did whites. In models adjusted for demographics, socioeconomic status, medications, health behaviors, neuroticism, and negative affect, a pervasive discrimination score of 2 versus 0 was associated with a greater AL score (b = 0.30, SE = 0.07, p < .001). Although associations seemed to be stronger among African Americans as compared with whites, associations did not statistically differ by race.

Conclusions
More pervasive discrimination was related to greater multisystemic physiological dysregulation in a cohort of African American and white adults. Measuring discrimination by combining multiple forms of discriminatory experiences may be important for studying the health effects of discrimination.
Emotional Pathways to the Biological Embodiment of Racial Discrimination Experiences
Authors: Hittner Emily F. , Adam Emma K. 
Published: February 2020

ABSTRACT

Objective
Racial discrimination experiences are common among youth with an ethnic minority background, and such experiences affect health. Stress-sensitive systems like the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as one mechanism. HPA-axis activity, measured through daily patterns of salivary cortisol, is altered among individuals who experience discrimination. We know little about the day-to-day processes by which discrimination experiences become embodied in stress biology. The HPA axis is responsive to negative social-evaluative (NSE) emotion. The present study investigated whether NSE emotions are a pathway by which discrimination dysregulates HPA-axis functioning as measured by cortisol levels.

Methods
Perceived discrimination, diurnal cortisol, and changes in NSE emotion were assessed in a sample of 102 young adults. Emotions and cortisol were measured across the day for seven consecutive days in naturalistic settings. Multilevel modeling and regression analyses were used to examine average and day-to-day associations between discrimination, NSE emotion, and cortisol. Mediation and specificity analyses were conducted.

Results
Discrimination was associated with NSE emotion (β = 0.34, p = .001). Day-to-day changes (β = 0.10, p = .002) and average levels (β = 0.03, p = .013) of NSE emotion were associated with dysregulated cortisol. NSE emotion mediated the association between discrimination and diurnal cortisol slopes (β = 0.10 [95% confidence interval = 0.01–0.21]). Findings were robust for covariates including stressful life events, more pronounced for NSE emotion compared with negative affect at the day level, similar for NSE emotion and general negative affect at the person level, and specific to cortisol slopes.

Conclusions
Findings suggest that daily NSE and average negative emotions are important pathways by which racial discrimination gets under the skin, or is embodied, in stress biology.
Quality and Safety in Healthcare, Part LXVI
Authors: Harolds Jay A. 
Published: February 2020

Abstract
Problems in the learning environment are the main contributing factors to medical student burnout. These issues include stresses from mistreatment, poor support, cynical supervisors, pressure to get good grades and learn a huge amount of information quickly, fatigue, lack of control, and so on. Personal risk factors include having been seriously ill recently, having a low grit score, being in debt, and having a job.
Neuro-Ophthalmic Injuries With Systemic Neurologic Injury or Traumatic Brain Injury in Operation Iraqi Freedom and Operation Enduring Freedom
Authors: Jaksha Alexandria F. , Justin Grant A. , Brooks Daniel I. , Elward Cameron J. , Ryan Denise S. , Weichel Eric D. , Colyer Marcus H. 
Published: February 2020

Background:To analyze the final visual acuity (VA) of neuro-ophthalmologic injuries (NOI) in combat ocular trauma and to study the association of NOI with systemic neurologic injury (SNI) and traumatic brain injury (TBI).Methods:The Walter Reed Ocular Trauma Database was reviewed. Inclusion criteria were any US service member and Department of Defense civilians who suffered NOI, SNI, or TBI in Operation Iraqi Freedom or Operation Enduring Freedom. The primary outcome measure was the rate of poor final VA in patients with an NOI with secondary outcome measures the rate of SNI and TBI. in patients with NOI.Results:One hundred seventy-eight (20.00%) of 890 eyes had an NOI. Optic nerve injury was observed in 79 (44.38%) eyes, other cranial nerve injury in 68 (38.20%), Horner syndrome in 4 (2.25%), diplopia in 45 (25.28%), and ptosis in 13 (7.30%). In patients with NOI, 76 (42.69%) eyes had a final VA less than 20/200. In injured eyes (n = 359) of patients (n = 251) with TBI, 154 eyes (34.26%) had a final VA less than 20/200. In multivariate analysis, optic nerve injury (P< 0.001), unlike TBI (P= 0.47), was associated with final VA less than 20/200. SNI (n = 229) had a statistically significant association (odds ratio 29.8, 95% confidence interval 19.2–47.8,P< 0.001) with NOI. Optic nerve injury and cranial nerve injury were associated with TBI and SNI (all,P< 0.001).Conclusion:Optic nerve injury and cranial nerve injury are associated with TBI and SNI. Optic nerve injury, but not TBI or cranial nerve injury, is associated with a poor final VA.
Bacterial immune evasion proteins: The therapeutic potential of CHIPS
Authors: Tromp Angelino T. , Zhao Yuxi , Jongerius Ilse , Heezius Erik C.J.M , Abrial Pauline , Ruyken Maartje , van Strijp Jos A. G. , de Haas Carla.J.C. , Spaan András N. , van Kessel Kok P.M. , Henry Thomas , Haas Pieter-Jan A. 
Published: February 2020

AbstractBacterial pathogens have evolved to secrete strong anti-inflammatory proteins that target the immune system. It was long speculated whether these virulence factors could serve as therapeutics in diseases in which abnormal immune activation plays a role. We adopted the secreted Chemotaxis Inhibitory Protein of Staphylococcus aureus (CHIPS) as a model virulence factor-based therapeutic agent for diseases in which C5aR1 stimulation plays an important role. We show that administration of CHIPS in human C5aR1 knock-in mice successfully dampens C5a mediated neutrophil migration during immune complex-initiated inflammation. Subsequent CHIPS toxicology studies in animal models were promising. However, during a small phase-I trial, healthy human volunteers showed adverse effects directly after CHIPS administration. Subjects showed clinical signs of anaphylaxis with mild leukocytopenia and increased C-reactive protein concentrations, suggesting an inflammatory response, which are believed to be related to the presence of relatively high circulating anti-CHIPS antibodies. Even though our data in mice shows CHIPS as a potential anti-inflammatory agent, safety issues in human subjects temper the use of CHIPS in its current form as a therapeutic candidate. The use of staphylococcal proteins, or other bacterial proteins, as therapeutics or immune-modulators in humans is severely hampered by pre-existing circulating antibodies.
Foxm1 regulates neuronal progenitor fate during spinal cord regeneration
Authors: Pelzer Diane , Phipps Lauren S. , Thuret Raphael , Baker Syed Murtuza , Dorey Karel 
Published: February 2020

SummaryMammals have limited tissue regeneration capabilities, particularly in the case of the central nervous system. Spinal cord injuries are often irreversible and lead to the loss of motor and sensory function below the site of the damage [1]. In contrast, amphibians such asXenopustadpoles can regenerate a fully functional tail, including their spinal cord, following amputation [2,3]. A hallmark of spinal cord regeneration is the re-activation of Sox2/3+ progenitor cells to promote regrowth of the spinal cord and the generation of new neurons [4,5]. In axolotls, this increase in proliferation is tightly regulated as progenitors switch from a neurogenic to a proliferative division via the planar polarity pathway (PCP) [6–8]. How the balance between self-renewal and differentiation is controlled during regeneration is not well understood. Here, we took an unbiased approach to identify regulators of the cell cycle expressed specifically inX.tropicalisspinal cord after tail amputation by RNAseq. This led to the identification of Foxm1 as a potential key transcription factor for spinal cord regeneration.Foxm1-/-X.tropicalistadpoles develop normally but cannot regenerate their spinal cords. Using single cell RNAseq and immunolabelling, we show thatfoxm1+ cells in the regenerating spinal cord undergo a transient but dramatic change in the relative length of the different phases of the cell cycle, suggesting a change in their ability to differentiate. Indeed, we show that Foxm1 does not regulate the rate of progenitor proliferation but is required for neuronal differentiation leading to successful spinal cord regeneration.
Recreation of an antigen-driven germinal center in vitro by providing B cells with phagocytic antigen
Authors: Martínez-Riaño Ana , Delgado Pilar , Mendoza Pilar , Oeste Clara L. , Abia David , Rodríguez-Bovolenta Elena , Turner Martin , Alarcón Balbino 
Published: February 2020

SUMMARYSuccessful vaccines rely on activating a functional humoral response that results from generating class-switched high affinity immunoglobulins (Igs) with a superior capacity to neutralize infection. Key to this process is the germinal center (GC) reaction, in which B cells are selected in their search for antigen and T cell help. A major hurdle to understanding the mechanisms of B cell:T cell cooperation has been the lack of anin vitrosystem to recreate GCs in an antigen-specific manner. Here we report the generation of functional antigen-specific high affinity Igs of different isotypes in simple 2-cell type cultures of naïve B and T cells. It is crucial for this process for B cells to take up antigen by a phagocytic mechanism, which results in stronger and more sustained BCR signals compared to stimulation with a soluble antigen. We also show the applicability of the system to generate antibodies of potential clinical interest.
Continuum theory of active phase separation in cellular aggregates
Authors: Kuan Hui-Shun , Pönisch Wolfram , Jülicher Frank , Zaburdaev Vasily 
Published: February 2020

AbstractDense cellular aggregates are common in many biological settings, ranging from bacterial biofilms to organoids, cell spheroids and tumors. Motivated byNeisseria gonorrhoeaebiofilms as a model system, we present a hydrodynamic theory to study dense, active, viscoelastic cellular aggregates. The dynamics of these aggregates, driven by forces generated by individual cells, is intrinsically out-of-equilibrium. Starting from the force balance at the level of individual cells, we arrive at the dynamic equations for the macroscopic cell number density via a systematic coarse-graining procedure taking into account a nematic tensor of intracellular force dipoles. We describe the basic process of aggregate formation as an active phase separation phenomenon. Our theory furthermore captures how two cellular aggregates coalesce. Merging of aggregates is a complex process exhibiting several time scales and heterogeneous cell behaviors as observed in experiments. In our theory, it emerges as a coalescence of active viscoelastic droplets where the key timescales are linked to the turnover of the active force generation. Our theory provides a general framework to study the rheology and dynamics of dense cellular aggregates out of thermal equilibrium.
Drug GRADE: an integrated analysis of population growth and cell death reveals drug-specific and cancer subtype-specific response profiles
Authors: Schwartz Hannah R. , Richards Ryan , Fontana Rachel E. , Joyce Anna J. , Honeywell Megan E. , Lee Michael J. 
Published: February 2020

ABSTRACTIn the pre-clinical evaluation of anti-cancer drugs, two different measurement approaches are used: relative viability, which scores an amalgam of growth arrest and cell death, and fractional viability, which more specifically scores the degree of cell killing. In this study, we directly quantify relationships between drug-induced growth inhibition and drug-induced cell death by counting live and dead cells over time using quantitative microscopy. We find that most drugs affect both growth and death, but with different proportions and with different relative timing. These features lead to a non-uniform and unpredictable relationship between the canonical relative and fractional drug response measurements. To unify these disparate measurements, we create a new data visualization and data analysis platform, called drug GRADE, which characterizes the degree to which cell death contributes to an observed reduction in population size for any given drug. Our new method reveals both drug- and genotype-specific drug responses, which are not captured using traditional pharmaco-metrics. Taken together, this study highlights the extremely idiosyncratic nature of drug-induced growth and cell death and provides a new analysis tool for quantitatively evaluating these behaviors.
Myocardial damage induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart
Authors: Forte Elvira , Panahi Mona , Ng Fu Siong , Boyle Joseph J. , Branca Jane , Bedard Olivia , Hasham Muneer G. , Benson Lindsay , Harding Sian E. , Rosenthal Nadia , Sattler Susanne 
Published: February 2020

AbstractHeart failure is the common final pathway of a range of conditions resulting in myocardial damage and a major cause of morbidity and mortality worldwide. Strategies to improve tissue repair and prevent heart failure thus remain an urgent clinical need. Recent studies have documented activation of the adaptive immune system in response to myocardial damage and have implicated anti-heart autoimmunity in the development of heart failure. In an attempt to target anti-heart autoimmune responses as new therapeutic avenue, the number of experimental studies usingin vivomodels of myocardial damage to study the ensuing immune response has surged.The beta-adrenergic agonist isoproterenol-hydrochloride has been used for its cardiac effects in a variety of different dosing and administration regimes. Most prominently, low doses (<10mg/kg sc) over an extended time period induce cardiac hypertrophy and fibrosis. In addition, single injections of high doses (>100mg/kg) induce cardiomyocyte necrosis and have been used to mimic acute myocardial necrotic lesions as seen in myocardial infarction (MI). However, despite significant resource and animal welfare advantages, concerns about off-target effects and clinical relevance have so far limited uptake in the cardiovascular research community.To assess suitability of the isoproterenol model for the analysis of chronic post-MI immunological readouts, we treated C57BL/6J mice with a single intra-peritoneal bolus injection of 160mg/kg isoproterenol. Our results confirm the presence of necrotic lesions in the myocardium with significant resemblance of the histopathology of Type 2 MI. Kidneys develop mild fibrosis secondary to early cardiac damage, while other organs remain unaffected. Most importantly, we showed that isoproterenol treatment causes myocardial inflammation and fibrosis, activation of T cells in the heart-draining mediastinal lymph nodes, deposition of mature antibodies in the myocardium and the presence of auto-antibodies against the heart in the serum 12 weeks after the initial injury.In summary, this simple and cost-effective experimental model with significant animal welfare benefits induces myocardial damage reminiscent of human Type 2 MI, which is followed by a persistent adaptive immune response against the heart. This makes it a suitable and high-throughput model to study pathological mechanisms of anti-heart autoimmunity as well as to test potential immunomodulatory therapeutic approaches.
Widefield light sheet microscopy using an Airy beam combined with deep-learning super-resolution
Authors: Corsetti Stella , Wijesinghe Philip , Poulton Persephone B. , Sakata Shuzo , Vyas Khushi , Herrington C. Simon , Nylk Jonathan , Gasparoli Federico , Dholakia Kishan 
Published: February 2020

AbstractImaging across length scales and in depth has been an important pursuit of widefield optical imaging. This promises to reveal fine cellular detail within a widefield snapshot of a tissue sample. Current advances often sacrifice resolution through selective sub-sampling to provide a wide field of view in a reasonable time scale. We demonstrate a new avenue for recovering high-resolution images from sub-sampled data in light-sheet microscopy using deep-learning super-resolution. We combine this with the use of a widefield Airy beam to achieve high-resolution imaging over extended fields of view and depths. We characterise our method on fluorescent beads as test targets. We then demonstrate improvements in imaging amyloid plaques in a cleared brain from a mouse model of Alzheimer’s disease, and in excised healthy and cancerous colon and breast tissues. This development can be widely applied in all forms of light sheet microscopy to provide a two-fold increase in the dynamic range of the imaged length scale. It has the potential to provide further insight into neuroscience, developmental biology and histopathology.
Sequence-based Prediction of Metamorphic Behavior in Proteins
Authors: Chen N. , Das M. , LiWang A. , Wang L.-P. 
Published: February 2020

AbstractAn increasing number of proteins have been demonstrated in recent years to adopt multiple three-dimensional folds with different functions. These metamorphic proteins are characterized by having two or more folds with significant differences in their secondary structure, where each fold is stabilized by a distinct local environment. So far, about 90 metamorphic proteins have been identified in the Protein Databank (PDB), but we and others hypothesize that a far greater number of metamorphic proteins remain undiscovered. In this work, we introduce a computational model to predict metamorphic behavior in proteins using only knowledge of the sequence. In this model, secondary structure prediction programs are used to calculatediversity indices, which are measures of uncertainty in predicted secondary structure at each position in the sequence; these are then used to assign protein sequences as likely to be metamorphic vs. monomorphic (i.e. having just one-fold). We constructed a reference dataset to train our classification method, which includes a novel compilation of 140 likely-monomorphic proteins, and a set of 201 metamorphic proteins taken from the literature. Our model is able to classify proteins as metamorphic vs. monomorphic with a Matthews correlation coefficient of ∼0.4 and true positive / true negative rates of ∼65% / 80%, suggesting that it is possible to predict metamorphic behavior in proteins using only sequence information.Statement of SignificanceThis paper introduces the diversity index as a descriptor to distinguish metamorphic proteins, which possess multiple stable folds, from monomorphic proteins that possess only one fold. The diversity index is designed to measure uncertainty in computationally predicted secondary structure, which we hypothesize is elevated for metamorphic proteins. We tested our hypothesis by training a binary classifier using the diversity index and an annotated dataset of metamorphic and monomorphic proteins, and found an optimal Matthews correlation coefficient of 0.4, supporting the hypothesis and demonstrating for the first time that it is possible to predict metamorphic behavior in proteins using only sequence information. The sequence-based classifier has broader applicability compared to methods that rely on making comparison to experimentally measured structures.
SkewIT: Skew Index Test for detecting mis-assembled bacterial genomes
Authors: Lu Jennifer , Salzberg Steven L 
Published: February 2020

AbstractGC skew is a phenomenon observed in many bacterial genomes, wherein the two replication strands of the same chromosome contain different proportions of guanine and cytosine nucleotides. Here we demonstrate that this phenomenon, which was first discovered in the mid-1990s, can be used today as an analysis tool for the 15,000+ complete bacterial genomes in NCBI’s Refseq library. In order to analyze all 15,000+ genomes, we introduce a new method, SkewIT (Skew Index Test), which calculates a single metric representing the degree of GC skew for a genome. Using this metric, we demonstrate how GC skew patterns are conserved within certain bacterial phyla, e.g. Firmicutes, but show different patterns in other phylogenetic groups such as Actinobacteria. We also discovered that outlier values of SkewIT highlight potential bacterial mis-assemblies. Using our newly defined metric, we identify multiple mis-assembled chromosomal sequences in NCBI’s Refseq library of complete bacterial genomes.Software AvailabilitySkewIT scripts for analysis of bacterial genomes are provided in the following repository: https://github.com/jenniferlu717/SkewIT.
Instrumented immobilizing boot quantifies reduced Achilles tendon loading during gait
Authors: Hullfish Todd J , O’Connor Kathryn M. , Baxter Josh R. 
Published: February 2020

ABSTRACTAchilles tendon ruptures are common injuries that lead to functional deficits in two-thirds of patients. Progressively loading the healing tendon has been associated with superior outcomes, but the loading profiles that patients experience throughout rehabilitation have not yet been established. In this study, we developed and calibrated an instrumented immobilizing boot paradigm that is aimed at longitudinally quantifying patient loading biomechanics to develop personalized rehabilitation protocols. We used a 3-part instrumented insole to quantify the ankle loads generated by the Achilles tendon and secured a load cell in-line with the posterior strut of the immobilizing boot to quantify boot loading. We then collected gait data from five healthy young adults to demonstrate the validity of this instrumented immobilizing boot paradigm to assess Achilles tendon loading during ambulation. We developed a simple calibration procedure to improve the measurement fidelity of the instrumented insole needed to quantify Achilles tendon loading while ambulating with an immobilizing boot. By assessing Achilles tendon loading with the ankle constrained to 0 degrees and 30 degrees plantar flexion, we confirmed that walking with the foot supported in plantar flexion decreased Achilles tendon loading by 60% (P< 0.001). This instrumented immobilizing boot paradigm leverages commercially available sensors and logs data using a small microcontroller secured to the boot and a handheld device, making our paradigm capable of continuously monitoring biomechanical loading outside of the lab or clinic.