bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining county-level counterfactuals for evaluation of population health interventions: A novel application ofK-means cluster analysis
Authors: Strutz Kelly L. , Luo Zhehui , Raffo Jennifer E. , Meghea Cristian I. , Meulen Peggy Vander , Roman Lee Anne 
Published: May 2020

AbstractObjectivesEvaluating population health initiatives at the community level necessitates valid counterfactual communities, which includes having similar complexity with respect to population composition, healthcare access, and health determinants. Estimating appropriate county counterfactuals is challenging in states with large inter-county variation. We present and discuss an application ofK-means cluster analysis for determining county-level counterfactuals in an evaluation of a county perinatal system of care for Medicaid-insured pregnant women.Materials and MethodsCounties were described using indicators from the American Community Survey, Area Health Resources Files, University of Wisconsin Population Health Institute County Health Rankings, and vital records for Michigan Medicaid-insured births for the year intervention began (or the closest available year). We ran analyses of 1,000 iterations with random starting cluster values for each of a range of number of clusters from 3 to 10 and used standard variability and reliability measures to identify the optimal number of clusters.ResultsOne county was grouped with the intervention county in all solutions for all iterations and thus considered most valid for 1:1 population county comparisons. Two additional counties were frequently grouped with the intervention county. However, no county was ideal for all subpopulation analyses.Practice ImplicationsAlthough the K-means method was successful at identifying a comparison county, concerning intervention-comparison differences remained. This limitation of the method may be specific to this county and the constraints of a within-state study. This method could potentially be more useful when applied to other counties in and outside of Michigan.
Beyond predicting the number of infections: predicting who is likely to be COVID negative or positive
Authors: Zhang Stephen X. , Sun Shuhua , Jahanshahi Asghar Afshar , Wang Yifei , Madavani Abbas Nazarian , Dinani Maryam Mokhtari 
Published: May 2020

ABSTRACTThis study provides the first attempt to identify people at greater risk of COVID-19 infection, enabling more targeted infectious disease prevention and control, which are especially important in the ongoing shortage of COVID-19 testing.We conducted a primary survey of 521 adults on April 1-10, 2020 in Iran, where the official infection rate was 0·08%. In our sample, 3% reported being COVID-19 positive and 15% were unsure of their status. This relatively high positive rate enabled us to conduct the analysis at the 5% significance level.At the time of the survey, 44% of the adults worked from home; 26% still went to work in their workplaces; 27% had stopped working due to the COVID-19 pandemic; and 3% were unemployed. Adults who exercised more were more likely to be COVID-19 negative. Each additional hour of exercise per day predicted a 78% increase in the likelihood of being COVID-19 negative. Adults with chronic medical illnesses were 48% more likely to be COVID-19 negative. In terms of work situation, those who worked from home were the most likely to be COVID-19 negative, and those who had stopped working were the most likely to be COVID-19 positive. Individuals in larger organizations were less likely to be COVID-19 positive.Given the testing shortage in many countries, we identify a novel approach to predict the likelihood of COVID-19 infection by a set of personal and work situation characteristics, in order to help to identify individuals with more or less risk of contracting the virus. We hope this research opens a new research avenue to identify the individual risk factors of COVID-19 infection to enable more targeted infectious disease prevention, communication, testing, and control to complement the effort to expand testing capacity.
Evaluation of effects of public health interventions on COVID-19 transmission for Pakistan: A mathematical simulation study
Authors: Bhutta Zulfiqar A , Harari Ofir , Park Jay JH , Zannat Noor-E , Zoratti Michael , Churches Tim , Thorlund Kristian , Mills Edward J 
Published: May 2020

AbstractBackgroundIn an effort to contain the COVID-19 epidemic, many governments across the world have enforced lockdown or social distancing measures. Several outbreak models have been developed to investigate the effects of different public health strategies for COVID-19, but they have not been developed for Pakistan and other South East Asian countries, where a large proportion of global population resides.MethodsWe developed a stochastic individual contact model by extending the widely-used Susceptible-Infectious-Recovered (SIR) compartment model with additional compartments to model both anticipated mitigating effects of public health intervention strategies for Pakistan. We estimated the projected spread, number of hospitalizations, and case fatalities under no intervention and four increasingly stringent public health strategies of social distancing and self-isolation at the national and provincial levels of Pakistan.ResultsOur analysis shows that without any public health interventions the expected number of cumulative case fatalities is 671,596 in Pakistan with the virus is expected to peak in terms of the number of required ICU-hospitalizations at 198,593 persons by the end of the June 2020. The estimated total numbers of cumulative case fatalities are lower for other public health strategies with strict social distancing showing the lowest number of deaths at 1,588 (Self-isolation: n=341,359; Flexible social distancing strategy: n=3,995; and Exit strategy: n=28,214). The lowest number of required ICU-hospitalization is also estimated for strict social distancing strategy (n=266 persons at the end of May 2020). Generally, the simulated effects of the different public health strategies at the provincial-level were similar to the national-level with strict social distancing showing the fewest number of case fatalities and ICU-hospitalizations.ConclusionOur results indicate that case fatalities and ICU-hospitalizations for Pakistan will be high without any public health interventions. While strict social distancing can potentially prevent a large number of deaths and ICU-hospitalizations, the government faces an important dilemma of potentially severe economic downfall. Consideration of a temporary strict social distancing strategy with gradual return of the lower-risk Pakistani population, as simulated in our exit strategy scenario, may an effective compromise between public health and economy of Pakistani population.
AutoAudio: Deep Learning for Automatic Audiogram Interpretation
Authors: Crowson Matthew G. , Lee Jong Wook , Hamour Amr , Mahmood Rafid , Babier Aaron , Lin Vincent , Tucci Debara L. , Chan Timothy C.Y. 
Published: May 2020

AbstractObjectivesHearing loss is the leading human sensory system loss, and one of the leading causes for years lived with disability with significant effects on quality of life, social isolation, and overall health. Coupled with a forecast of increased hearing loss burden worldwide, national and international health organizations have urgently recommended that access to hearing evaluation be expanded to meet demand.MethodsThe objective of this study was to develop ‘AutoAudio’ – a novel deep learning proof-of-concept model that accurately and quickly interprets diagnostic audiograms. Adult audiogram reports representing normal, conductive, mixed and sensorineural morphologies were used to train different neural network architectures. Image augmentation techniques were used to increase the training image set size. Classification accuracy on a separate test set was used to assess model performance.ResultsThe architecture with the highest out-of-training set accuracy was ResNet-101 at 97.5%. Neural network training time varied between 2 to 7 hours depending on the depth of the neural network architecture. Each neural network architecture produced misclassifications that arose from failures of the model to correctly label the audiogram with the appropriate hearing loss type. The most commonly misclassified hearing loss type were mixed losses.ConclusionRe-engineering the process of hearing testing with a machine learning innovation may help enhance access to the growing worldwide population that is expected to require audiologist services. Our results suggest that deep learning may be a transformative technology that enables automatic and accurate audiogram interpretation.
Neutrophil extracellular traps and thrombosis in COVID-19
Authors: Zuo Yu , Zuo Melanie , Yalavarthi Srilakshmi , Gockman Kelsey , Madison Jacqueline A. , Shi Hui , Knight Jason S. , Kanthi Yogendra 
Published: May 2020

ABSTRACTHere, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.
Risk Factors of the Severity of COVID-19: a Meta-Analysis
Authors: Rahman Abdur , Sathi Nusrat Jahan 
Published: May 2020

ABSTRACTBACKGROUNDAlthough the infection rate of COVID-19 is very high, all the patients getting infected don’t always die or go through brutal states. This indicates there may be some factors that possibly boost the severity of COVID-19.OBJECTIVEWe intend to identify some probable risk factors that are responsible for the severity of COVID-19 using a meta-analysis.METHODSThe literature exploration lasted up to 18 April 2020 and through PubMed, Google Scholar, EMBASE, and Cochrane Library we have identified 10 pertinent publications. To paraphrase the outcomes of autonomous researches, we have performed a random-effect meta-analysis.RESULTSA total of 2272 patients’ information was extracted from the selected literature. We have found sex (male) (Risk ratio [RR] =1.29 [1.07; 1.54]), hypertension (RR=1.79 [1.57; 2.04]), diabetes (RR=1.57 [1.25; 1.98]), fatigue or myalgia (RR=1.17 [1.02; 1.35]), and smoking history (RR=1.71 [1.25; 2.35]) are potential risk factors for the severity of COVID-19. We found fever (RR=1.21 [0.66; 2.22]), cough (1.13 [0.98; 1.30]), and diarrhea (RR=1.14 [0.93; 1.40]) as insignificant risk factors for COVID-19 severity.CONCLUSIONThe findings of this research may be beneficial to identify patients with higher risks to provide additional medical attention from the very beginning of the treatment.
A molecular atlas of proximal airway identifies subsets of known airway cell types revealing details of the unique molecular pathogenesis of Cystic Fibrosis
Authors: Carraro Gianni , Langerman Justin , Sabri Shan , Lorenzana Zareeb , Purkayastha Arunima , Konda Bindu , Aros Cody J. , Calvert Ben A. , Szymaniak Aleks , Wilson Emily , Mulligan Michael , Bhatt Priyanka , Vijayaraj Preethi , Yao Changfu , Shia David W. , Israely Edo , Rickabaugh Tammy M. , Mense Martin , Randell Scott H. , Vladar Eszter K. , Ryan Amy L. , Plath Kathrin , Mahoney John , Stripp Barry R. , Gomperts Brigitte N. 
Published: May 2020

Introduction/AbstractCystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts in excess of 70,000 people globally. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most significant determinant of morbidity and mortality. In this study we report results from a multi-institute consortium in which single cell transcriptomics were applied to define disease-related changes to the proximal airway of CF donors (n=19) undergoing transplantation for end-stage lung disease compared to the proximal airway of previously healthy lung donors (n=19). We found that all major airway epithelial cell types were conserved between control and CF donors. Disease-dependent differences were observed, including an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subtypes coupled with an unexpected decrease in cycling basal cells. This study developed a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.
Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Authors: Jamal Alainna J. , Mozafarihashjin Mohammad , Coomes Eric , Powis Jeff , Liu Angel Xin , Paterson Aimee , Anceva-Sami Sofia , Barati Shiva , Crowl Gloria , Faheem Amna , Farooqi Lubna , Khan Saman , Prost Karren , Poutanen Susan , Yip Lily , Zhong Zoe , McGeer Allison J. , Mubareka Samira ,   for the Toronto Invasive Bacterial Diseases Network COVID-19 Investigators
Published: May 2020

AbstractWe enrolled 53 consecutive in-patients with COVID-19 at six hospitals in Toronto, Canada, and tested one nasopharyngeal swab/saliva sample pair from each patient for SARS-CoV-2. Overall, sensitivity was 89% for nasopharyngeal swabs and 77% for saliva (p=NS); difference in sensitivity was greatest for sample pairs collected later in illness.
Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19
Authors: Patterson Bruce K. , Seethamraju Harish , Dhody Kush , Corley Michael J. , Kazempour Kazem , Lalezari Jay , Pang Alina P.S. , Sugai Christopher , Francisco Edgar B. , Pise Amruta , Rodrigues Hallison , Ryou Mathew , Wu Helen L. , Webb Gabriela M. , Park Byung S. , Kelly Scott , Pourhassan Nader , Lelic Alena , Kdouh Lama , Herrera Monica , Hall Eric , Aklin Enver , Ndhlovu Lishomwa C. , Sacha Jonah B. 
Published: May 2020

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date1. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation2. Emerging results indicate a dysregulated immune response characterized by runaway inflammation, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-193,4. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation in severe disease caused by SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Following compassionate care treatment with the CCR5 blocking antibody leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.
Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission
Authors: Laha Sayantan , Chakraborty Joyeeta , Das Shantanab , Manna Soumen Kanti , Biswas Sampa , Chatterjee Raghunath 
Published: May 2020

ABSTRACTThe recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.
HIV Protease Inhibitor Nelfinavir Targets Human DDI2 and Potentiates Proteasome Inhibitor-based Chemotherapy
Authors: Gu Yuan , Wang Xin , Wang Yu , Li Jie , Yu Fa-Xing 
Published: May 2020

AbstractProteasome inhibitors (PIs) are currently used in the clinic to treat cancers such as multiple myeloma (MM). However, cancer cells often rapidly develop drug resistance towards PIs due to a compensatory mechanism mediated by nuclear factor erythroid 2 like 1 (NFE2L1) and aspartic protease DNA damage inducible 1 homolog 2 (DDI2). Following DDI2-mediated cleavage, NFE2L1 is able to induce transcription of virtually all proteasome subunit genes. Under normal condition, cleaved NFE2L1 is constantly degraded by proteasome, whereas in the presence of PIs, it accumulates and induces proteasome synthesis which in turn promotes the development of drug resistance towards PIs. Here, we report that Nelfinavir (NFV), an HIV protease inhibitor, can inhibit DDI2 activity directly. Inhibition of DDI2 by NFV effectively blocks NFE2L1 proteolysis and potentiates cytotoxicity of PIs in cancer cells. Recent clinical evidence indicated that NFV can effectively delay the refractory period of MM patients treated with PI-based therapy. Our finding hence provides a specific molecular mechanism for combinatorial therapy using NFV and PIs for treating MM and probably additional cancers.Abstract Figure
Rapid T cell receptor interaction grouping with ting
Authors: Mölder Felix , Stervbo Ulrik , Loyal Lucie , Bacher Petra , Babel Nina , Rahmann Sven 
Published: May 2020

AbstractMotivationClustering of antigen-specific T cell receptor repertoire (TCRR) sequences is challenging. The recently published tool GLIPH aims to solve this problem. However, clustering large repertoires takes several days to weeks, making its use impractical in larger studies. In addition, the methodology used in GLIPH suffers from several shortcomings, including non-determinism, potential loss of significant antigen-specific sequences or inclusion of too many unspecific sequences.ResultsWe present an algorithm for clustering TCRR sequences that scales efficiently to large repertoires. We clustered 26 real datasets with up to 62 000 unique CDR3βsequences using both GLIPH and an implementation of our method called ting. While GLIPH required multiple weeks, ting only needed about one hour for the same task. In addition, we found that in naïve repertoires, where no or very few antigen-specific CDR3 sequences or clusters should exist, our method indeed selects fewer sequences.AvailabilityOur method has been implemented in Python as a tool called ting, using numpy and NetworkX. It is available on GitHub (https://github.com/FelixMoelder/ting) and on PyPI under the MIT license.Contactfelix.moelder@uni-due.deorsven.rahmann@uni-due.de
Mechanistic insights into RNA binding and RNA-regulated RIG-I ubiquitination by TRIM25
Authors: Haubrich Kevin , Augsten Sandra , Álvarez Lucía , Huppertz Ina , Simon Bernd , Perez Kathryn , Masiewicz Pawel , Lethier Mathilde , Rittinger Katrin , Gabel Frank , Hentze Matthias W. , Cusack Stephen , Hennig Janosch 
Published: May 2020

ABSTRACTTRIM25 is a ubiquitin E3 ligase active in innate immunity and cell fate decisions. Mounting evidence suggests that TRIM25′s E3 ligase activity is regulated by RNAs. However, while mutations affecting RNA binding have been described, neither the precise RNA binding site has been identified nor which domains are involved. Here, we present biophysical evidence for the presence of RNA binding sites on both TRIM25 PRY/SPRY and coiled-coil domains, and map the binding site on the PRY/SPRY with residue resolution. Cooperative RNA-binding of both domains enhances their otherwise transient interaction in solution and increases the E3 ligase activity of TRIM25. We also show that TRIM25 not only binds RNA in mammalian cells but that interfering with RNA binding has an effect on cellular RIG-I ubiquitination.
A gradient of Wnt activity positions the neurosensory domains of the inner ear
Authors: Żak Magdalena , Plagnol Vincent , Daudet Nicolas 
Published: May 2020

AbstractThe auditory and vestibular organs of the inner ear and the neurons that innervate them originate from Sox2-positive and Notch-active neurosensory domains specified at early stages of otic development. Sox2 is initially present throughout the otic placode and otocyst, then it becomes progressively restricted to a ventro-medial domain. Using gain and loss-of-function approaches in the chicken otocyst, we show that these early changes in Sox2 expression are regulated in a dose-dependent manner by Wnt/beta-catenin signalling. Both high and very low levels of Wnt activity repress Sox2 and neurosensory competence. However, intermediate levels allow the maintenance of Sox2 expression and sensory organ formation. We propose that a dorso-ventral (high-to-low) gradient and wave of Wnt activity initiated at the dorsal rim of the otic placode progressively restricts Sox2 and Notch activity to the ventral half of the otocyst, thereby positioning the neurosensory competent domains in the inner ear.