bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Incidence of Venous Thrombosis in Patients with Moderate to Severe COVID-19
Authors: Kerbikov Oleg B. , Orekhov Pavel Yu. , Borskaya Ekaterina N. , Nosenko Natalia S. 
Published: June 2020

ABSTRACTCOVID-19 predisposes to venous thromboembolism and there are multiple data regarding high incidence of venous thrombosis in critical COVID-19 patients, however reports on this complication in less severe patients are not widely available.The aim of this study was to investigate the incidence of deep-vein thrombosis (DVT) in patients with moderate to severe COVID-19 and to assess the prevalence of DVT with lung computerized tomography (lung CT) exams, clinical information and lab data. This study examined 75 consecutive patients with moderate to severe COVID-19, with specific exclusions.METHODSAlmost all patients (pts) admitted to our hospital in the first half of May underwent comprehensive vein ultrasonography. 75 pts (aged 27-92 y, median – 63 y, 36 males and 39 females) with moderate to severe COVID-19 were included in our study.RESULTSSpontaneous echo contrast (decreased blood velocity and blood stasis) was detected in common femoral veins in 53 pts (70.7%). DVT was found in 15 pts (20%). The vast majority of those with DVT (13 pts, 86.7%) had thrombi only in calf veins and ileofemoral thrombosis was detected in 2 pts with DVT (13.3%). There was no significant observed difference between DVT and non-DVT patients with respect to age, underlying diseases, lung CT scores and SpaO2 at admission. There was also no significant observed difference between DVT and non-DVT patients with respect to both “time from symptoms onset to admission” and with respect to the majority of lab data.However, a significant difference was observed in D-dimer level (1.87 ± 1.62 vs 0.51 ± 0,4 mcg/mL p<0.0001) and C-reactive protein (116.9 ± 83,6 and 65.1 ± 64.98 mg/L, p = 0.014) for patients with DVT and patients without DVT respectably (Receiver operating characteristics (ROC) curve analysis revealed that the level of D-dimer ≥ 0.69 mcg/mL is the predictor of DVT with a sensitivity of 76.9%, a specificity of 77.6%, p < 0.001 (AUC area under curve = 0.7944). Logistic regression confirmed that D-dimer is an independent predictor of DVT and patients with D-dimer ≥ 0.69 mcg/mL have odds ratio (OR) of developing DVT = 5.1 (confidence interval [CI] 1.9 - 13.5)).CONCLUSIONPatients with moderate to severe COVID-19 show high incidence of DVT, indicating that moderate to severe COVID-19 patients may require an early administration of anticoagulation therapy as part of their treatment. Such therapy may be continued after hospital discharge. Based on these findings, these patients may also require a follow-up with vein ultrasonography after recovery to rule out DVT.
Developing an automatic pipeline for analyzing chatter about health services from social media: A case study for Medicaid
Authors: Yang Yuan-Chi , Al-Garadi Mohammed Ali , Hogg-Bremer Whitney , Zhu Jane M. , Grande David , Sarker Abeed 
Published: June 2020

AbstractObjectiveSocial media can be an effective but challenging resource for conducting close-to-real-time assessments of consumers’ perceptions about health services. Our objective was to develop and evaluate an automatic pipeline, involving natural language processing and machine learning, for automatically characterizing user-posted Twitter data about Medicaid.Material and MethodsWe collected Twitter data via the public API using Medicaid-related keywords (Corpus-1), and the website’s search option using agency-specific handles (Corpus-2). We manually labeled a sample of tweets into five pre-determined categories or other, and artificially increased the number of training posts from specific low-frequency categories. We trained and evaluated several supervised learning algorithms using manually-labeled data, and applied the best-performing classifier to collected tweets for post-classification analyses assessing the utility of our methods.ResultsWe collected 628,411 and 27,377 tweets for Corpus-1 and -2, respectively. We manually annotated 9,571 (Corpus-1: 8,180; Corpus-2: 1,391) tweets, using 7,923 (82.8%) for training and 1,648 (17.2%) for evaluation. A BERT-based (bidirectional encoder representations from transformers) classifier obtained the highest accuracies (83.9%, Corpus-1; 86.4%, Corpus-2), outperforming the second-best classifier (SVMs: 79.6%; 76.4%). Post-classification analyses revealed differing inter-corpora distributions of tweet categories, with political (63%) and consumer-feedback (43%) tweets being most frequent for Corpus-1 and -2, respectively.Discussion and ConclusionThe broad and variable content of Medicaid-related tweets necessitates automatic categorization to identify topic-relevant posts. Our proposed pipeline presents a feasible solution for automatic categorization, and can be deployed/generalized for health service programs other than Medicaid. Annotated data and methods are available for future studies (LINK_TO_BE_AVAILABLE).
Burnout among healthcare professionals during COVID-19 pandemic: a cross-sectional study
Authors: Jalili Mohammad , Niroomand Mahtab , Hadavand Fahimeh , Zeinali Kataun , Fotouhi Akbar 
Published: June 2020

AbstractBackgroundThe unpredictable nature of the new COVID-19 pandemic and the already alarming incidence of healthcare workers being affected can have a significant impact on the psychological well-being of the staff.ObjectiveTo describe the prevalence of burnout among healthcare professionals and the associated factors.DesignCross-sectional survey.SettingEight university affiliated hospitals in the capital city of Tehran, Iran.ParticipantsAll healthcare workers at the study sites who had been taking care of COVID-19 patients.MeasurementsAge, gender, marital status, having children, hospital, job category, experience, and work load, as well as the level of burnout in each subscale.Results326 persons (53.0%) experienced high levels of burnout. The average score in emotional exhaustion, depersonalization and lack of personal accomplishment was 26.6, 10.2, and 27.3, respectively. The level of burnout in the three subscales varied based on the personal as well as work related factors and gender was the only variable that was associated with high levels of all three domains.LimitationsThere was no control group and thus we cannot claim a causal relationship between COVID-19 and the observed level of burnout. Not all confounding factors might have been accounted for.ConclusionsBurnout is prevalent among healthcare workers caring for COVID-19 patients. Age, gender, job category, and site of practice contribute to the level of burnout that the staff experience.Funding sourceNone
A Logistic Model for Age-Specific COVID-19 Case-Fatality Rates
Authors: Gao Xiang , Dong Qunfeng 
Published: June 2020

ABSTRACTObjectivesTo develop a mathematical model to characterize age-specific case-fatality rates (CFR) of COVID-19.Materials and MethodBased on two large-scale Chinese and Italian CFR data, a logistic model was derived to provide quantitative insight on the dynamics between CFR and age.Results and DiscussionWe inferred that CFR increased faster in Italy than in China, as well as in females over males. In addition, while CFR increased with age, the rate of growth eventually slowed down, with a predicted theoretical upper limit for males (32%), females (21%), and the general population (23%).ConclusionOur logistic model provided quantitative insight on the dynamics of CFR.Lay SummaryRecently published studies have qualitatively shown that the COVID-19 case-fatality rates increased with age, with elder people at higher risk of fatality than younger ones. In our study, we presented a quantitative mathematical modeling approach to re-analyze those published data. Specifically, we were able to derive a logistic model to characterize age-specific CFRs. The derived mathematical model uncovered novel quantitative insights on the dynamics between CFR and age. Specifically, we inferred from the model that while CFR increased with age, the rate of growth eventually slowed down, with a predicted theoretical upper limit of 23% for the general population.
Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic
Authors: Zhang Wenjuan , Govindavari John Paul , Davis Brian , Chen Stephanie , Kim Jong Taek , Song Jianbo , Lopategui Jean , Plummer Jasmine T , Vail Eric 
Published: June 2020

AbstractGiven the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5’UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10% of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50% of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.
Population density and basic reproductive number of COVID-19 across United States counties
Authors: Sy Karla Therese L. , White Laura F. , Nichols Brooke 
Published: June 2020

AbstractThe basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0of SARS-CoV-2 across U.S. counties, and whether population density could be used as a proxy for contact rates. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0. We also assessed whether this association was differential across county-level main mode of transportation-to-work percentage. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. The effect of population density and R0was not modified by private transportation use. Differential R0by population density can assist in more accurate predictions of the rate of spread of SARS-CoV-2 in areas that do not yet have active cases.Article Summary LineU.S. counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density.
Nr2e3functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates Retinitis Pigmentosa and Enhanced S-cone Syndrome models
Authors: Aísa-Marín Izarbe , López-Iniesta M José , Milla Santiago , Lillo Jaume , Navarro Gemma , de la Villa Pedro , Marfany Gemma 
Published: June 2020

ABSTRACTMutations inNR2E3cause retinitis pigmentosa (RP) and enhanced S-cone syndrome (ESCS) in humans. This gene produces a large isoform encoded in 8 exons and a previously unreported shorter isoform of 7 exons, whose function is unknown. We generated two mouse models by targeting exon 8 ofNr2e3using CRISPR/Cas9-D10A nickase. Allele Δ27 is an in-frame deletion of 27 bp that ablates the dimerization domain, whereas allele ΔE8 (full deletion of exon 8), produces only the short isoform that lacks the dimerization and repressor domains. The Δ27 mutant shows developmental alterations and a non-progressive electrophysiological dysfunction that resembles the ESCS phenotype. The ΔE8 mutant exhibits progressive retinal degeneration, as occurs in human RP patients. Interestingly, the mutant retinas show invaginations similar to fovea-like pits. Our mutants suggest a role ofNr2e3as a cone-patterning regulator and provide valuable models for studying mechanisms ofNR2E3-associated retinal dystrophies and evaluating potential therapies.Abstract FigureHighlights-Nr2e3mouse models were generated by exon 8 deletion using CRISPR/Cas9 D10A nickase.- NewNr2e3mRNA retaining intron 7 encodes a short protein expressed in adult retina.- Deletion of 9 aa of the NR2E3 dimerization domain causes enhanced S-cone syndrome.- Deletion of exon 8 produces a phenotype similar to Retinitis Pigmentosa in mouse.
Prrx1b directs pro-regenerative fibroblasts during zebrafish heart regeneration
Authors: de Bakker Dennis E.M. , Dronkers Esther , Bouwman Mara , Vink Aryan , Goumans Marie-José , Smits Anke M. , Bakkers Jeroen 
Published: June 2020

ABSTRACTRationaleThe human heart loses millions of cardiomyocytes after an ischemic injury, but is unable to regenerate the lost tissue. Instead, the injured human heart is repaired by pro-fibrotic fibroblasts that form a large permanent scar. In contrast, the injured zebrafish heart regenerates efficiently without the formation of a permanent scar. While fibroblasts have been shown to be indispensable for zebrafish heart regeneration, very little is known about the mechanisms balancing the fibrotic and regenerative response. A better understanding of these mechanisms could lead to the discovery of novel therapeutic strategies to reduce fibrosis and promote heart regeneration.ObjectiveTo identify novel mechanisms that regulate the balance between cardiac fibrosis and scar-free regeneration.Methods and ResultsUsing a genetic approach, we first show that zebrafishprrx1bloss-of-function mutants display reduced cardiomyocyte proliferation and impaired heart regeneration. Using a lineage tracing approach, we show that Prrx1b is expressed intcf21+ epicardial-derived cells localizing around and inside the injured area. Next, we used a single cell RNA-sequencing approach on sortedtcf21+ cells isolated from injuredprrx1b-/- and wild-type hearts and identified two distinct fibroblast populations. With combined bioinformatic and histological analysis we found thatprrx1b-/- hearts contain an excess of pro-fibrotic fibroblasts that produce TGF-β ligands and collagens, while fewer pro-regenerative Nrg1-expressing fibroblasts are formed. Furthermore, by injecting recombinant NRG1 inprrx1b-/- fish we were able to rescue their cardiomyocyte proliferation defect. Finally, using cultured human fetal epicardial cells and siRNA mediated knock-down of PRRX1 we found that PRRX1 is required for NRG1 induction in human epicardial-derived cells.ConclusionsPrrx1b in the injured heart restricts fibrosis and stimulates regeneration by directing epicardial-derived cells towards a pro-regenerative Nrg1-producing fibroblast state.
Comparative genomics ofChlamydomonas
Authors: Craig Rory J. , Hasan Ahmed R. , Ness Rob W. , Keightley Peter D. 
Published: June 2020

AbstractDespite its fundamental role as a model organism in plant sciences, the green algaChlamydomonas reinhardtiientirely lacks genomic resources for any closely related species, obstructing its development as a study system in several fields. We present highly contiguous and well-annotated genome assemblies for the two closest known relatives of the species,Chlamydomonas incertaandChlamydomonas schloesseri, and a third more distantly related species,Edaphochlamys debaryana. We find the threeChlamydomonasgenomes to be highly syntenous with similar gene contents, although the 129.2 MbC. incertaand 130.2 MbC. schloesseriassemblies are more repeat-rich than the 111.1 MbC. reinhardtiigenome. We identify the major centromeric repeat inC. reinhardtiias an L1 LINE transposable element homologous to Zepp (the centromeric repeat inCoccomyxa subellipsoidea) and infer that centromere locations and structure are likely conserved inC. incertaandC. schloesseri. We report extensive rearrangements, but limited gene turnover, between the minus mating-type loci of theChlamydomonasspecies, potentially representing the early stages of mating-type haplotype reformation. We produce an 8-species whole-genome alignment of unicellular and multicellular volvocine algae and identify evolutionarily conserved elements in theC. reinhardtiigenome. We find that short introns (<~100 bp) are extensively overlapped by conserved elements, and likely represent an important functional class of regulatory sequence inC. reinhardtii. In summary, these novel resources enable comparative genomics analyses to be performed forC. reinhardtii, significantly developing the analytical toolkit for this important model system.
Heritable Genetic Background Alters Survival and Phenotype ofMll-AF9-Induced Leukemias
Authors: Young Kira , Loberg Matthew A. , Eudy Elizabeth , Schwartz Logan S. , Mujica Kristina D. , Trowbridge Jennifer J. 
Published: June 2020

AbstractThe MLL-AF9 fusion protein occurring as a result of t(9;11) translocation gives rise to pediatric and adult acute leukemias of distinct lineages, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and mixed phenotype acute leukemia (MPAL). The mechanisms underlying how this same fusion protein results in diverse leukemia phenotypes among different individuals is not well understood. Given emerging evidence from genome-wide association studies (GWAS) that genetic risk factors contribute toMLL-rearranged leukemogenesis, here we tested the impact of genetic background on survival and phenotype of a well-characterizedMll-AF9knockin mouse model. We crossed this model to five distinct inbred strains (129, A/J, C57BL/6, NOD, CAST), and tested their F1 hybrid progeny for dominant genetic effects onMll-AF9phenotypes. We discovered that genetic background altered peripheral blood composition, withMll-AF9CAST F1 demonstrating significantly increased B lymphocyte frequency while the remainder of the strains exhibited myeloid-biased hematopoiesis, similar to the parental line. Genetic background also impacted overall survival, withMll-AF9A/J F1 andMll-AF9129 F1 having significantly shorter survival, andMll-AF9CAST F1 having longer survival, compared to the parental line. Furthermore, we observed a range of hematologic malignancies, withMll-AF9A/J F1,Mll-AF9129 F1 andMll-AF9B6 F1 developing exclusively myeloid cell malignancies (myeloproliferative disorder (MPD) and AML) whereas a subset ofMll-AF9NOD F1 developed MPAL andMll-AF9CAST F1 developed ALL. This study provides a novelin vivoexperimental model to evaluate the underlying mechanisms by whichMLL-AF9results in diverse leukemia phenotypes and provides definitive experimental evidence that genetic risk factors contribute to survival and phenotype ofMLL-rearranged leukemogenesis.
Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons
Authors: Gowrishankar Swetha , Lyons Lila , Rafiq Nisha Mohd , Roczniak-Ferguson Agnes , De Camilli Pietro , Ferguson Shawn M. 
Published: June 2020

AbstractThe dependence of neurons on microtubule-based motors for the movement of lysosomes over long distances raises questions about adaptations that allow neurons to meet these demands. Recently, JIP3/MAPK8IP3, a neuronally enriched putative adaptor between lysosomes and motors, was identified as a critical regulator of axonal lysosome abundance. In this study, we establish a human induced pluripotent stem cell (iPSC)-derived neuron model for the investigation of axonal lysosome transport and maturation and show that loss of JIP3 results in the accumulation of axonal lysosomes and the Alzheimer’s disease-related amyloid precursor protein (APP)-derived Aβ42 peptide. We furthermore reveal an overlapping role of the homologous JIP4 gene in lysosome axonal transport. These results establish a cellular model for investigating the relationship between lysosome axonal transport and amyloidogenic APP processing and more broadly demonstrate the utility of human iPSC-derived neurons for the investigation of neuronal cell biology and pathology.
Redox stress reshapes carbon fluxes ofPseudomonas putidafor cytosolic glucose oxidation and NADPH generation
Authors: Nikel Pablo I. , Fuhrer Tobias , Chavarría Max , Sánchez-Pascuala Alberto , Sauer Uwe , de Lorenzo Víctor 
Published: June 2020

AbstractThe soil bacterium and metabolic engineering platformPseudomonas putidatolerates high levels of endogenous and exogenous oxidative stress, yet the ultimate reason of such property remains unknown. To shed light on this question, NADPH generation routes—the metabolic currency that fuels redox stress responses—were assessed whenP. putidaKT2440 was challenged with H2O2as proxy of oxidative conditions.13C-tracer experiments, metabolomics and flux analysis, together with inspection of physiological parameters and measurement of enzymatic activities, revealed a substantial flux reconfiguration under oxidative stress. In particular, periplasmic glucose processing was rerouted to cytoplasmic oxidation, and cyclic operation of the pentose phosphate pathway led to significant NADPH fluxes, exceeding biosynthetic demands by ~50%. This NADPH surplus, in turn, fuelled the glutathione system for H2O2reduction. These properties not only contribute to the tolerance ofP. putidato environmental stresses, but they also highlight the value of this host for harsh biotransformations.
Coronavirus genomes carry the signatures of their habitats
Authors: Wei Yulong , Silke Jordan R. , Aris Parisa , Xia Xuhua 
Published: June 2020

ABSTRACTCoronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of COVID-19. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter deaminates C into U residues leading to dysfunctional transcripts. We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas viruses that do not infect tissues with abundant AVPs do not share these sequence hallmarks. In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Furthermore, over four months of SARS-CoV-2 evolutionary history, we observed a marked increase in C to U substitutions in the 5’ UTR and ORF1ab regions. This suggests that the two regions could be under constant C to U deamination by APOBEC3. The evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.