bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection
Authors: Lala Anuradha , Johnson Kipp W , Januzzi James , Russak Adam J , Paranjpe Ishan , Zhao Shan , Somani Sulaiman , Vaid Akhil , Chaudhry Fayzan , Freitas Jessica K De , Richter Felix , Fayad Zahi A , Pinney Sean P. , Levin Matthew , Charney Alexander , Bagiella Emilia , Narula Jagat , Glicksberg Benjamin S , Nadkarni Girish , Mancini Donna M. , Fuster Valentin 
Published: April 2020

STRUCTURED ABSTRACTBackgroundThe degree of myocardial injury, reflected by troponin elevation, and associated outcomes among hospitalized patients with Coronavirus Disease (COVID-19) in the US are unknown.ObjectivesTo describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.MethodsPatients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value <0.03ng/mL) measured within 24 hours of admission were included (n=2,736). Demographics, medical history, admission labs, and outcomes were captured from the hospitals’ EHR.ResultsThe median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. Even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were associated with death (adjusted HR: 1.77, 95% CI 1.39-2.26; P<0.001) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were associated with more pronounced risk (adjusted HR 3.23, 95% CI 2.59-4.02).ConclusionsMyocardial injury is prevalent among patients hospitalized with COVID-19, and is associated with higher risk of mortality. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation likely reflects non-ischemic or secondary myocardial injury.Unstructured AbstractMyocardial injury reflected as elevated troponin in Coronavirus Disease (COVID-19) is not well characterized among patients in the United States. We describe the prevalence and impact of myocardial injury among hospitalized patients with confirmed COVID-19 and troponin-I measurements within 24 hours of admission (N=2,736). Elevated troponin concentrations (normal <0.03ng/mL) were commonly observed in patients hospitalized with COVID-19, most often present at low levels, and associated with increased risk of death. Patients with cardiovascular disease (CVD) or risk factors for CVD were more likely to have myocardial injury. Troponin elevation likely reflects non-ischemic or secondary myocardial injury.
COVID-19 pandemic scenario in India compared to China and rest of the world: a data driven and model analysis
Authors: Mandal Manisha , Mandal Shyamapada 
Published: April 2020

AbstractThe COVID-19 is a rapidly spreading respiratory illness caused with the infection of SARS-CoV-2. The COVID-19 data from India was compared with China and rest of the world. The average values of daily growth rate (DGR), case recovery rate (CRR), case fatality rate (CFR), serial interval (SI) of COVID-19 in India was 17%, 8.25%, and 1.87%, and 5.76 days respectively, as of April 9, 2020. The data driven estimates of basic reproduction number (R0), average reproduction number (R) and effective reproduction number (Re) were 1.03, 1.73, and 1.35, respectively. The results of exponential and SIR model showed higher estimates of R0, R and Re. The data driven as well as estimated COVID-19 cases reflect the growing nature of the epidemic in India and world excluding China, whereas the same in China reveal the involved population became infected with the disease and moved into the recovered stage. The epidemic size of India was estimated to be ∼30,284 (as of April 15, 2020 with 12,370 infectious cases) with an estimated end of the epidemic on June 9, 2020. The Re values in India before and after lockdown were 1.62 and 1.37 respectively, with SI 5.52 days and 5.98 days, respectively, as of April 17, 2020, reflecting the effectiveness of lockdown strategies. Beyond April 17, 2020, our estimate of 24,431 COVID-19 infected cases with lockdown is 78% lower compared to the 112,042 case estimates in absence of lockdown, on April 27, 2020. To early end of the COVID-19 epidemic, strong social distancing is important.
The Association of Lymphocyte count and levels of CRP, D-Dimer, and LDH with severe coronavirus disease 2019 (COVID-19): A Meta-Analysis
Authors: Ali Almigdad H. M. , Mohamed Sagad Omer Obeid , Elkhidir Ibrahim H. E. , Elbathani Mohamed Elata Hassan , Ibrahim Abazr A. H. , Elhassan Almutasim B. E. , Salman Mohammed Suliman Tawer , Elhassan Mazin A.M. , Elnil Mahmoud , Abuzied Abdelhamid Ibrahim Hassan 
Published: April 2020

AbstractThe rapid progression of Coronavirus disease 2019 (COVID-19) and its increasing burden on health systems necessitate the identification of parameters of severe infection to help in monitoring, prognoses and development of treatment algorithms. This review aims to investigate the association of lymphocyte count, CRP, LDH, and D-Dimer with the severe form of COVID-19. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, WHO-Virtual Health Library (VHL), and ScienceDirect were used for the systematic search. Random effects model was used to estimate the pooled standardized mean differences (SMD) with the corresponding 95% confidence interval (CI), using OpenMeta Analyst software. A total of 11 studies, with 2437 COVID-19 patients, which fulfilled the eligibility criteria were included in the meta-analysis. The analysis revealed that lymphocyte count was significantly lower in patients with the severe form of COVID-19 (SMD = - 1.025, P value <.001). Also, the analysis of SMD showed that patients with severe COVID-19 have a significantly higher serum levels of CRP (SMD = 3.363, P value <.001), D-Dimer (SMD = 1.073, P value <.001), and LDH (SMD = 3.345, P value <.001). Low lymphocyte count and high levels of CRP, LDH, and D-Dimer are associated with severe COVID-19. These laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of COVID-19.
African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer
Authors: Karunamuni Roshan , Huynh-Le Minh-Phuong , Fan Chun , Thompson Wesley , Eeles Rosalind , Kote-Jarai Zsofia , Muir Kenneth ,   UKGPCS collaborators, Lophatananon Artitaya , Tangen Catherine , Goodman Phyllis , Thompson Ian , Blot William , Zheng Wei , Kibel Adam , Drake Bettina , Cussenot Olivier , Cancel-Tassin Geraldine , Menegaux Florence , Truong Therese , Park Jong , Lin Hui-Yi , Bensen Jeannette , Fontham Elizabeth , Mohler James , Taylor Jack , Multigner Luc , Blanchet Pascal , Brureau Laurent , Romana Marc , Leach Robin , John Esther , Fowke Jay , Bush William , Aldrich Melinda , Crawford Dana , Srivastava Shiv , Cullen Jennifer , Petrovics Gyorgy , Parent Marie-Elise , Hu Jennifer , Sanderson Maureen , Mills Ian , Andreassen Ole , Dale Anders , Seibert Tyler M ,   The PRACTICAL Consortium
Published: April 2020

AbstractIntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46), showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify SNPs that might improve performance in this population.Material and MethodsAnonymized genotypic data were obtained from the PRACTICAL consortium for 6,253 men with African genetic ancestry. Ten iterations of a ten-fold cross-validation search were conducted, to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African were compared using the same cross-validated approach.ResultsThree SNPs (rs76229939, rs74421890, and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47 to 4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65 to 0.53).ConclusionsWe identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans and Asians. A strategy of building on established statistical models might benefit ancestral groups generally under-represented in genome-wide association studies.
Evolution of reproductive traits have no apparent life-history associated cost in populations ofDrosophila melanogasterselected for cold shock resistance
Authors: Singh Karan , Prasad Nagaraj Guru 
Published: April 2020

AbstractIn insect species likeDrosophila melanogaster, the ability to evolve greater resistance or evolution of certain traits under specific environmental conditions leads to energy trade-offs with other important life-history traits. A number of studies from multiple fields have documented the life-history associated cost. However, no known studies have assessed the life-history associated cost with evolved reproductive traits and increase egg viability in cold shock selected population. To explore this, we used replicate populations ofD. melanogasterthat have evolved reproductive traits and egg viability in response to increased resistance to non lethal cold shock. To assess life-history cost; we measured longevity, life time fecundity, Larvae to adults development time, and larvae to adults survival. We found that there were no significant differences in longevity, life time fecundity, larvae to adults survival, and male body weight between the selected and control populations. However, selected populations have significantly longer pre adults developmental time compared to their control population. Females from the selected populations were bigger in size compared to the control populations. These findings suggest that there is no life-history cost associated with the evolution of greater resistance in the aspect of faster recovery of egg viability and reproductive traits post cold-shock. It quite possible the cost of the evolution of reproductive traits and egg viability in response to cold shock resistant is paid in terms of reduced resistance to other stresses
Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection
Authors: McBurney-Lin Jim , Sun Yina , Tortorelli Lucas S. , Nguyen Quynh Anh , Haga-Yamanaka Sachiko , Yang Hongdian 
Published: April 2020

AbstractThe brain neuromodulatory systems heavily influence behavioral and cognitive processes. Previous work has shown that norepinephrine (NE), a classic neuromodulator mainly derived from the locus coeruleus (LC), enhances neuronal responses to sensory stimuli. However, the role of the LC-NE system in modulating perceptual task performance is not well understood. In addition, systemic perturbation of NE signaling has often been proposed to specifically target the LC in functional studies, yet the assumption that localized (specific) and systemic (nonspecific) perturbations of LC-NE have the same behavioral impact remains largely untested. In this study, we trained mice to perform a head-fixed, quantitative tactile detection task, and administered an α2 adrenergic receptor agonist or antagonist to pharmacologically down- or up-regulate LC-NE activity, respectively. We addressed the outstanding question of how bidirectional perturbations of LC-NE activity affect tactile detection, and tested whether localized and systemic drug treatments exert the same behavioral effects. We found that both localized and systemic suppression of LC-NE impaired tactile detection by reducing motivation. Surprisingly, while locally activating LC-NE enabled mice to perform in a near-optimal regime, systemic activation impaired behavior by promoting impulsivity. Our results demonstrate that localized silencing and activation of LC-NE differentially affect tactile detection, and that localized and systemic NE activation induce distinct behavioral changes.
Unifying the mechanism of mitotic exit control in a spatio-temporal logical model
Authors: Howell R. S. M. , Klemm C. , Thorpe P. H. , Csikász-Nagy A. 
Published: April 2020

1AbstractThe transition from mitosis into the first gap phase of the cell cycle in budding yeast is controlled by the Mitotic Exit Network (MEN). The network interprets spatio-temporal cues about the progression of mitosis and ensures that release of Cdc14 phosphatase occurs only after completion of key mitotic events. The MEN has been studied intensively however a unified understanding of how localization and protein activity function together as a system is lacking. In this paper we present a compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity. Through optimization of the model, we reveal insights into role of Cdc5 in Cdc15 localization and the importance of Lte1 regulation in control of Bfa1. We show that our model is capable of correctly predicting the phenotype of∼80% of mutants we tested, including mutants representing mislocalizing proteins. We use a continuous time implementation of the model to demonstrate the role of Cdc14 Early Anaphase Release (FEAR) to ensure robust timing of anaphase and verify our findings in living cells. We show that our model can represent measured cell-cell variation in Spindle Position Checkpoint (SPoC) mutants. Finally, we use the model to predict the impact of forced localization of MEN proteins and validate these predictions experimentally. This model represents a unified view of the mechanism of mitotic exit control.
Combining eye tracking with EEG: Effects of filter settings on EEG for trials containing task relevant eye-movements
Authors: Kulke Louisa , Kulke Vincent 
Published: April 2020

Co-registration of electroencephalography (EEG) and eye movements is becoming increasingly popular, as technology advances. This new method has several advantages, including the possibility of testing non-verbal populations and infants. However, eye movements can create artefacts in EEG data. Previous methods to remove eye-movement artefacts, have used high-pass filters before data processing. However, the role of filter settings for eye-artefact exclusion has not directly been investigated. The current study examined the effect of filter settings on EEG recorded in a dataset containing task-relevant eye movements. Part 1 models the effects of filters on eye-movement artifacts and part 2 demonstrates this effect on an EEG dataset containing task-relevant eye-movements. It shows that high-pass filters can lead to significant distortions and create artificial responses that are unrelated to the target. In conclusion, high-pass filter settings of 0.1 or lower can be recommended for EEG studies involving task-relevant eye movements.HighlightsCo-registration of EEG and eye-tracking is gaining popularityHowever, eye movements can create artifacts in the EEG signalThe current paper models the effect of high pass filters on eye-movement artifactsHigh pass filters can induce large distortions in EEG data containing regular eye-movementsThe distortion is affected by fixation duration and filter frequency
Lipid specificity of the immune effector perforin
Authors: Hodel Adrian W. , Rudd-Schmidt Jesse A. , Trapani Joseph A. , Voskoboinik Ilia , Hoogenboom Bart W. 
Published: April 2020

AbstractPerforin is a pore forming protein used by cytotoxic T lymphocytes to remove cancerous or virus-infected cells during immune response. During the response, the lymphocyte membrane becomes refractory to perforin function by accumulating densely ordered lipid rafts and externalizing negatively charged lipid species. The dense membrane packing lowers the capacity of perforin to bind, and negatively charged lipids scavenge any residual protein before pore formation. Using atomic force microscopy on model membrane systems, we here provide insight into the molecular basis of perforin lipid specificity.
Fused in sarcoma regulates DNA replication timing and progression
Authors: Jia Weiyan , Scalf Mark A. , Tonzi Peter , Millikin Robert J. , Kim Sang Hwa , Guns William M. , Liu Lu , Mastrocola Adam S. , Smith Lloyd M. , Huang Tony T. , Tibbetts Randal S. 
Published: April 2020

AbstractFused in sarcoma (FUS) encodes a low complexity RNA-binding protein with diverse roles in transcriptional activation and RNA processing. While oncogenic fusions of FUS and transcription factor DNA-binding domains are associated with soft tissue sarcomas, dominant mutations in FUS cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). FUS has also been implicated in DNA double-strand break repair (DSBR) and genome maintenance. However, the underlying mechanisms are unknown. Here we employed quantitative proteomics, transcriptomics, and DNA copy number analysis (Sort-Seq), in conjunction withFUS-/-cells to ascertain roles of FUS in genome protection.FUS-/-cells exhibited alterations in the recruitment and retention of DSBR factors BRCA1 and 53BP1 but were not overtly sensitive to genotoxins. By contrast, FUS-deficient cells had reduced proliferative potential that correlated with reduced replication fork speed, diminished loading of pre-replication complexes, and attenuated expression of S-phase associated genes. FUS interacted with lagging strand DNA synthesis factors and other replisome components, but did not translocate with active replication forks. Using a Sort-Seq workflow, we show that FUS contributes to genome-wide control of DNA replication timing and is essential for the early replication of transcriptionally active DNA. These findings illuminate new roles for FUS in DNA replication initiation and timing that may contribute to genome instability and functional defects in cells harboring disease-associated FUS fusions.
Sequence-dependent correlated segments in the intrinsically disordered region of ChiZ
Authors: Hicks Alan , Escobar Cristian A. , Cross Timothy A. , Zhou Huan-Xiang 
Published: April 2020

AbstractIntrinsically disordered proteins (IDPs) account for a significant fraction of any proteome and are central to numerous cellular functions. Yet how sequences of IDPs code for their conformational dynamics is poorly understood. Here we combined NMR spectroscopy, small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulations to characterize the conformations and dynamics of ChiZ1-64. This IDP is the N-terminal fragment (residues 1-64) of the transmembrane protein ChiZ, a component of the cell division machinery inMycobacterium tuberculosis. Its N-half contains most of the prolines and all of the anionic residues while the C-half most of the glycines and cationic residues. MD simulations, first validated by SAXS and secondary chemical shift data, found scant α-helices or β-strands but considerable propensity for polyproline II (PPII) torsion angles. Importantly, several blocks of residues (e.g., 11-29) emerge as “correlated segments”, identified by frequent formation of PPII stretches, salt bridges, cation-π interactions, and sidechain-backbone hydrogen bonds. NMR relaxation experiments showed non-uniform transverse relaxation rates (R2s) and nuclear Overhauser enhancements (NOEs) along the sequence (e.g., highR2s and NOEs for residues 11-14 and 23-28). MD simulations further revealed that the extent of segmental correlation is sequence-dependent: segments where internal interactions are more prevalent manifest elevated “collective” motions on the 5-10 ns timescale and suppressed local motions on the sub-ns timescale. Amide proton exchange rates provides corroboration, with residues in the most correlated segment exhibiting the highest protection factors. We propose correlated segment as a defining feature for the conformation and dynamics of IDPs.
Tumor secreted extracellular vesicles regulate T-cell costimulation and can be manipulated to induce tumor specific T-cell responses
Authors: Zhao Xianda , Yuan Ce , Wangmo Dechen , Subramanian Subbaya 
Published: April 2020

SUMMARYTumor intrinsic factors negatively regulate tumor immune cell infiltration and function. Deciphering the underlying mechanisms is critical to improving immunotherapy in cancers. Our analyses of human colorectal cancer (CRC) immune profiles and tumor-immune cell interactions revealed that tumor cell secreted extracellular vesicles (TEVs) induced immunosuppression in CRC. Specifically, TEVs containing microRNA miR-424 suppressed the CD28-CD80/86 costimulatory pathway in tumor infiltrating T cells and dendritic cells. Modified TEVs with miR-424 knocked down enhanced T-cell mediated antitumor immune response in CRC tumor models and increased the response to immune checkpoint blockade therapies (ICBT). Intravenous injections of modified TEVs induced tumor antigen specific immune responses. Moreover, injections of modified TEVs boosted the ICBT efficacy in CRC models that mimic treatment refractory late-stage disease. Collectively, we demonstrate a critical role for TEVs in antitumor immune regulation and immunotherapy response, which could be developed as a novel treatment for ICBT resistant human CRC.
Side-Impact Collision: Mechanics of Obstacle Negotiation in Sidewinding Snakes
Authors: Astley Henry C. , Rieser Jennifer M. , Kaba Abdul , Paez Veronica M. , Tomkinson Ian , Mendelson Joseph R. , Goldman Daniel I. 
Published: April 2020

AbstractSnakes excel at moving through cluttered environments, and heterogeneities can be used as propulsive contacts for snakes performing lateral undulation. However, sidewinding, often associated with sandy deserts, cuts a broad path through the environment that may increase the vulnerability to obstacles. Our prior work demonstrated that sidewinding can be represented as a pair of orthogonal body waves (vertical and horizontal) that can be independently modulated to achieve high maneuverability and incline ascent, suggesting that sidewinders may also use template modulations to negotiate obstacles. To test this hypothesis, we recorded overhead video of four sidewinder rattlesnakes(Crotalus cerastes)crossing a line of vertical pegs placed in the substrate. Snakes used three methods to traverse the obstacles: a Propagate Through behavior in which the lifted moving portion of the snake was deformed around the peg and dragged through as the snake continued sidewinding (115/160 runs), Reversal turns that reorient the snake entirely (35/160), or switching to Concertina locomotion (10/160). The Propagate-Through response was only used if the anterior-most region of static contact would propagate along a path anterior to the peg, or if a new region of static contact could be formed near the head to satisfy this condition; otherwise, snakes could only use Reversal Turns or switch to Concertina locomotion. Reversal Turns allowed the snake to re-orient and either escape without further peg contact or resorting to Propagate Through. We developed an algorithm to reproduce the Propagate Through behavior in a robotic model using a modulation of the two-wave template. This range of behavioral strategies provides sidewinders with a versatile range of options for effectively negotiating obstacles in their natural habitat, as well as provide insights into the design and control of robotic systems dealing with heterogeneous habitats.