bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center
Authors: Santarpia Joshua L. , Rivera Danielle N. , Herrera Vicki , Morwitzer M. Jane , Creager Hannah , Santarpia George W. , Crown Kevin K. , Brett-Major David M. , Schnaubelt Elizabeth , Broadhurst M. Jana , Lawler James V. , Reid St. Patrick , Lowe John J. 
Published: March 2020

AbstractLack of evidence on SARS-CoV-2 transmission dynamics has led to shifting isolation guidelines between airborne and droplet isolation precautions. During the initial isolation of 13 individuals confirmed positive with COVID-19 infection, air and surface samples were collected in eleven isolation rooms to examine viral shedding from isolated individuals. While all individuals were confirmed positive for SARS-CoV-2, symptoms and viral shedding to the environment varied considerably. Many commonly used items, toilet facilities, and air samples had evidence of viral contamination, indicating that SARS-CoV-2 is shed to the environment as expired particles, during toileting, and through contact with fomites. Disease spread through both direct (droplet and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) are indicated, supporting the use of airborne isolation precautions.One Sentence SummarySARS-CoV-2 is shed during respiration, toileting, and fomite contact, indicating that infection may occur in both direct and indirect contact.
m6A RNA methylation regulates the fate of endogenous retroviruses
Authors: Chelmicki Tomasz , Roger Emeline , Teissandier Aurélie , Rucli Sofia , Dossin François , Dura Mathilde , Fouassier Camille , Lameiras Sonia , Bourc’his Deborah 
Published: March 2020

AbstractEndogenous retroviruses (ERVs) are abundant and heterogenous groups of integrated retroviral sequences that impact genome regulation and cell physiology throughout their RNA-centered life cycle1. Failure to repress ERVs is associated with cancer, infertility, senescence and neurodegenerative diseases2–4. Here, using an unbiased genome-scale CRISPR knockout screen in mouse embryonic stem cells, we identify m6A RNA methylation as a novel means of ERV restriction. Methylation of ERV mRNAs is catalyzed by the complex of methyltransferase-like METTL3/METTL145proteins whose depletion, along with their accessory subunits, WTAP and ZC3H13, led to increased mRNA abundance of Intracisternal A-particles (IAPs) and related ERVK elements specifically, by targeting their 5’UTR region. Using controlled auxin-dependent degradation of the METTL3/METTL14 enzymatic complex, we showed that IAP mRNA and protein abundance is dynamically and inversely correlated with m6A catalysis. By monitoring mRNA degradation rates upon METTL3/14 double degron, we further proved that m6A methylation destabilizes IAP transcripts. Finally, similarly to m6A writers, triple knockout of the m6A readers YTHDF1, DF2 and DF36increased IAP mRNA abundance. This study sheds light onto a novel function of RNA methylation in protecting cellular integrity by clearing reactive ERV-derived RNA species, which may be especially important when transcriptional silencing is less stringent.
Ghosts of a structured past: Impacts of ancestral patterns of isolation-by-distance on divergence-time estimation
Authors: Hancock Zachary B. , Blackmon Heath 
Published: March 2020

AbstractIsolation by distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to the potential for allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the product of the population size and the deme number. Next, we simulate whole genomes to obtain SNPs, and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. We conclude that studies estimating divergence times be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.
Piezo2, a pressure sensitive channel is expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses
Authors: Wang Jigong , Hamill Owen P. 
Published: March 2020

ABSTRACTPiezo2 expression in the normal, young adult mouse brain was examined using an anti-PIEZO2 Ab generated against a C-terminal fragment of the human PIEZO2 protein. As a positive control for Ab staining of mouse neurons, the Ab was shown to stain the majority (~90%) of mouse dorsal root ganglia (DRG) neurons, consistent with recent in situ hybridization and transcriptomic studies that also indicatePiezo2gene expression in ~90% mouse DRG neurons. As a negative control and stringent test for specificity, the Ab failed to stain DRG satellite glial cells, which do not expressPiezo2but rather its paralog,Piezo1. In slices of brains isolated from the same mice as the DRG, the Ab displayed high selectivity in staining only specific neuron types, including some pyramidal neurons in the neocortex and hippocampus, Purkinje cells in the cerebellar cortex, and most notably mitral cells within the olfactory bulb. Given the demonstrated role ofPiezo2channels in peripheral neurons as a low-threshold pressure sensor (i.e., ≤ 5 mm Hg) critical for gentle touch, proprioception, and the regulation of breathing and blood pressure, its expression in select brain neurons has interesting implications. In particular, we propose that the pressure sensitive channel may provide specific brain neurons with an intrinsic resonance that acts to synchronize their firing with the normal pulsatile changes in intracranial pressure (ICP) associated with breathing and cardiac cycles. This novel mechanism could serve to increase the robustness of the respiration entrained oscillations that have been recorded in both rodent and human brains across widely distributed neuronal networks. The idea of a “global rhythm” within the brain has been mainly related to the effect of nasal airflow activating mechanosensitive neurons within the olfactory epithelium, which in turn synchronize, through direct synaptic connections, mitral neurons within the olfactory bulb and then through their projections, the activity of neural networks in other brain regions, including the hippocampus and neocortex. Our proposed, non-synaptic, intrinsic resonance mechanism for tracking pulsatile ICP changes would have the advantage that spatially separated brain networks could be globally synchronized effectively at the speed of sound.
Photoperiod-dependent developmental reprogramming of the transcriptional response to seawater entry in Atlantic salmon (Salmo salar)
Authors: Iversen Marianne , Mulugeta Teshome , West Alexander , Jørgensen Even , Martin Samuel A. M. , Sandve Simen Rød , Hazlerigg David 
Published: March 2020

AbstractThe developmental transition of juvenile salmon from a freshwater resident morph (parr) to a seawater (SW) migratory morph (smolt) requires a range of physiological adaptations, including the capacity to hypo-osmoregulate. This process, known as smolting, involves both photoperiod-dependent preparative changes before SW is encountered, and activational changes stimulated by exposure to SW. To explore the relationship between these two aspects we undertook experiments in which physiological and transcriptomic responses to SW-challenge were assessed in fish that had experienced different histories of photoperiodic exposure. Compared to fish held on constant light (LL), exposure to short photoperiod (SP) dramatically impaired hypo-osmoregulation in SW, and was associated with extensive glucocorticoid-related changes in gill gene expression. Additionally, a major effect of photoperiodic history was observed in the transcriptional response of LL-acclimated fish to SW, with the response profiles of fish held on LL throughout life being quite distinctive from those of fish which had experienced an 8 week period of exposure to SP prior to return to LL (SPLL). These differences in profile likely reflect a diminishing role for NFAT-mediated responses in SPLL fish, as pathways linked to acute changes in cellular tonicity or intracellular calcium levels decline in importance with preparation for SW.
Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study
Authors: Zhang Yan , Cui Yanhui , Shen Minxue , Zhang Jianchu , Liu Ben , Dai Minhui , Chen Linli , Han Duoduo , Fan Yifei , Zeng Yanjun , Li Wen , Lin Fengyu , Li Sha , Chen Xiang , Pan Pinhua 
Published: March 2020

ABSTRACTBackgroundThe 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet.MethodsIn this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020.ResultsOf the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders.ConclusionsDiabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.
Early chest computed tomography to diagnose COVID-19 from suspected patients: A multicenter retrospective study
Authors: Miao Congliang , Jin Mengdi , Miao Li , Yang Xinying , Huang Peng , Xiong Huanwen , Huang Peijie , Zhao Qi , Du Jiang , Hong Jiang 
Published: March 2020

AbstractObjectiveThe purpose of this study is to distinguish the imaging features of COVID-19 with other chest infectious diseases and evaluate diagnostic value of chest CT for suspected patients.MethodsAdult suspected patients aged>18 years within 14 days who underwent chest CT scan and reverse-transcription polymerase-chain-reaction (RT-PCR) tests were enrolled. The enrolled patients were confirmed and grouped according to results of RT-PCR tests. The data of basic demographics, single chest CT features, and combined chest CT features were analyzed for confirmed and non-confirmed groups.ResultsA total of 130 patients were enrolled with 54 cases positive and 76 cases negative. The typical CT imaging features of positive group were ground glass opacity (GGO), crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally, close to the lower lungs or the pleura. When features combined, GGO with bilateral pulmonary distribution and GGO with pleural distribution were more common, of which were 31 cases (57.4%) and 30 cases (55.6%) respectively. The combinations were almost presented statistically significant (P<0.05) except for the combination of GGO with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations is around 90%.ConclusionsThe combinations of GGO could be useful in the identification and differential diagnosis of COVID-19, which alerts clinicians to isolate patients for treatment promptly and repeat RT-PCR tests until incubation ends.
Modes of contact and risk of transmission in COVID-19 among close contacts
Authors: Luo Lei , Liu Dan , Liao Xin-long , Wu Xian-bo , Jing Qin-long , Zheng Jia-zhen , Liu Fang-hua , Yang Shi-gui , Bi Bi , Li Zhi-hao , Liu Jian-ping , Song Wei-qi , Zhu Wei , Wang Zheng-he , Zhang Xi-ru , Chen Pei-liang , Liu Hua-min , Cheng Xin , Cai Miao-chun , Huang Qing-mei , Yang Pei , Yang Xing-fen , Han Zhi-gang , Tang Jin-ling , Ma Yu , Mao Chen 
Published: March 2020

AbstractBackgroundRapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated.MethodsWe included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts.ResultsAmong 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases.ConclusionsIn conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.
Global computational alignment of tumor and cell line transcriptional profiles
Authors: Warren Allison , Jones Andrew , Shibue Tsukasa , Hahn William C. , Boehm Jesse S. , Vazquez Francisca , Tsherniak Aviad , McFarland James M. 
Published: March 2020

AbstractCell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Identifying cell line models that best represent the features of particular tumor samples, as well as tumor types that lackin vitromodel representation, remain important challenges. Gene expression has been shown to provide rich information that can be used to identify tumor subtypes, as well as predict the genetic dependencies and chemical vulnerabilities of cell lines. However, direct comparisons of tumor and cell line transcriptional profiles are complicated by systematic differences, such as the presence of immune and stromal cells in tumor samples and differences in the cancer-type composition of cell line and tumor expression datasets. To address these challenges, we developed an unsupervised alignment method (Celligner) and applied it to integrate several large-scale cell line and tumor RNA-Seq datasets. While our method aligns the majority of cell lines with tumor samples of the same cancer type, it also reveals large differences in tumor/cell line similarity across disease types. Furthermore, Celligner identifies a distinct group of several hundred cell lines from diverse lineages that present a more mesenchymal and undifferentiated transcriptional state and which exhibit distinct chemical and genetic dependencies. This method could thus be used to guide the selection of cell lines that more closely resemble patient tumors and improve the clinical translation of insights gained from cell line models.
An artificial intelligence-based first-line defence against COVID-19: digitally screening citizens for risks via a chatbot
Authors: Martin Alistair , Nateqi Jama , Gruarin Stefanie , Munsch Nicolas , Abdarahmane Isselmou , Knapp Bernhard 
Published: March 2020

ABSTRACTTo combat the pandemic of the coronavirus disease (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma’s accuracy far exceeds that of simple “yes-no” questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online athttps://www.symptoma.com.
Effects of Controlled Dual Growth Factor Delivery on Bone Regeneration Following Composite Bone-Muscle Injury
Authors: Subbiah Ramesh , Cheng Albert , Ruehle Marissa A. , Hettiaratchi Marian H. , Bertassoni Luiz E. , Guldberg Robert E. 
Published: March 2020

AbstractThe objective of this study was to investigate the controlled release of two growth factors (BMP-2 and VEGF) as a treatment strategy for clinically challenging composite injuries, consisting of a segmental bone defect and volumetric muscle loss. This is the first investigation of dual growth factor delivery in a composite injury model using an injectable smart delivery system consisting of heparin microparticles and alginate gel. The loading efficiency of growth factors into these biomaterials was found to be >90%, revealing a strong affinity of VEGF and BMP-2 to heparin and alginate. The system could achieve simultaneous or sequential release of VEGF and BMP-2 by varying the loading strategy. Single growth factor delivery (VEGF or BMP-2 alone) significantly enhanced vascular growthin vitro. However, no synergistic effect was observed for dual growth factor (BMP-2 + VEGF) delivery. Effective bone healing was achieved in all treatment groups (BMP-2, simultaneous or sequential delivery of BMP-2 and VEGF) in the composite injury model. The mechanics of the regenerated bone reached a maximum strength of ∼52% of intact bone with sequential delivery of VEGF and BMP-2. Overall, simultaneous or sequential co-delivery of low-dose BMP-2 and VEGF failed to fully restore the mechanics of bone in this injury model. Given the severity of the composite injury, VEGF alone may not be sufficient to establish mature and stable blood vessels when compared with previous studies co-delivering BMP-2+VEGF enhanced bone tissue regeneration. Hence, future studies are warranted to develop an alternative treatment strategy focusing on better control over growth factor dose, spatiotemporal delivery, and additional growth factors to regenerate fully functional bone tissue.HighlightsWe developed a smart growth factor delivery system using heparin microparticles and alginate that facilitates tunable delivery of VEGF and BMP-2 in a simultaneous or sequential manner by merely varying the loading strategy.In vitro, both VEGF and BMP-2 alone promoted vascular growth; however, VEGF was significantly more potent, and there was no detectable benefit of co-delivery.In vivo, both BMP-2 alone and co-delivery of VEGF and BMP-2 promoted bone formation in the challenging bone/muscle polytrauma model; however, none of the treatment groups restored biomechanical properties to that of uninjured bone.
Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China
Authors: Hu Ling , Chen Shaoqiu , Fu Yuanyuan , Gao Zitong , Long Hui , Ren Hong-wei , Zuo Yi , Li Huan , Wang Jie , Xu Qing-bang , Yu Wen-xiong , Liu Jia , Shao Chen , Hao Jun-jie , Wang Chuan-zhen , Ma Yao , Wang Zhanwei , Yanagihara Richard , Wang Jian-ming , Deng Youping 
Published: March 2020

ABSTRACTBackgroundWith evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. As such, data are urgently needed about risk factors associated with clinical outcomes.MethodsA retrospective chart review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on their initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression.ResultsCurrent standard treatments did not show significant improvement on patient outcomes in the study. By univariate logistic regression model, 27 risk factors were significantly associated with clinical outcomes. Further, multivariate regression indicated that age over 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 × 109/L) and neutrophilia (>75 × 109/L) predicted unfavorable clinical outcomes. By contrast, the use of hypnotics was significantly associated with favorable outcomes. Survival analysis also confirmed that patients receiving hypnotics had significantly better survival.ConclusionsTo our knowledge, this is the first indication that hypnotics could be an effective ancillary treatment for COVID-19. We also found that novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.(Funded by the Natural Science Foundation of Hubei Province ZRMS2019000029 and the Top Youth Talent Program in Hubei Province.)