bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission dynamics of coronavirus disease 2019 outside of Daegu-Gyeongsangbuk provincial region in South Korea
Authors: Ryu Sukhyun , Ali Sheikh Taslim , Jang Cheolsun , Kim Baekjin , Cowling Benjamin J. 
Published: May 2020

AbstractWe analyzed transmission of coronavirus disease 2019 in South Korea. We estimated that non-pharamaceutical measures reduced the immediate transmissibility by maximum of 34% for coronavirus disease 2019. Continuous efforts are needed for monitoring the transmissibility to optimize epidemic control.
Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative
Authors: Zhou Yunying , Pei Fengyan , Wang Li , Zhao Huailong , Li Huanjie , Ji Mingyu , Yang Weihua , Wang Qingxi , Zhao Qianqian , Wang Yunshan 
Published: May 2020

ABSTRACTAn ongoing outbreak of pneumonia associated with SARS-CoV-2 has now been confirmed globally. In absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine is critical. Early detection and differential diagnosis of respiratory infections increases the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis with high sensitivity. However, the highest specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, a large amount of recent evidence indicates that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with “re-examination positive” may be due to low viral load, and the ability of rapid mutation of coronavirus also increases the rate of false negative results. We aimed to evaluate the sensitivity of different nucleic acid detection kits so as to make recommendations for the selection of validation kit, and amplify the suspicious result to be reportable positive by means of simple continuous amplification, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.
Pre-Existing Traits Associated with Covid-19 Illness Severity
Authors: Ebinger Joseph E. , Achamallah Natalie , Ji Hongwei , Claggett Brian L. , Sun Nancy , Botting Patrick , Nguyen Trevor-Trung , Luong Eric , Kim Elizabeth H. , Park Eunice , Liu Yunxian , Rosenberry Ryan , Matusov Yuri , Zhao Steven , Pedraza Isabel , Zaman Tanzira , Thompson Michael , Raedschelders Koen , Berg Anders H. , Grein Jonathan D. , Noble Paul W. , Chugh Sumeet S. , Merz C. Noel Bairey , Marbán Eduardo , Van Eyk Jennifer E. , Solomon Scott D. , Albert Christine M. , Chen Peter , Cheng Susan 
Published: May 2020

AbstractBackgroundCertain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.MethodsWe studied N=442 patients who presented with laboratory confirmed Covid-19 illness to our U.S. metropolitan healthcare system. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.ResultsOf all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P=0.001), African American (OR 2.1, P=0.011), obese (OR 2.0, P=0.021), with diabetes mellitus (OR 1.8, P=0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P=0.003) irrespective of age, race, or morbidity profile.ConclusionsIn our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.
Simple ventilators for emergency use based on Bag-Valve pressing systems: Lessons learned and future steps
Authors: Castro-Camus E. , Ornik J. , Mach C. , Hernandez-Cardoso G. G. , Savalia B. , Taiber J. , Ruiz-Marquez A. , Kesper K. , Konde S. , Sommer C. , Wiener J. , Geisel D. , Hüppe F. , Kräling G. , Nguyen J. , Wiesmann T. , Beutel B. , Koch M. 
Published: May 2020

ABSTRACTAs part of a plethora of global efforts to minimize the negative effects of the SARS-CoV2 (COVID-19) pandemic, we developed two different mechanisms that, after further development, could potentially be of use in the future in order to increase the capacity of ventilators with low-cost devices based on single-use-bag-valve mask systems. We describe the concept behind the devices and report a characterization of them. Finally, we make a description of the solved and unsolved challenges and propose a series of measures in order to better cope with future contingencies.
Forecasting Novel Corona Positive Cases in India using Truncated Information: A Mathematical Approach
Authors: Singh Brijesh P. 
Published: May 2020

AbstractNovel corona virus is declared as pandemic and India is struggling to control this from a massive attack of death and destruction, similar to the other countries like China, Europe, and the United States of America. India reported 2545 cases novel corona confirmed cases as of April 2, 2020 and out of which 191 cases were reported recovered and 72 deaths occurred. The first case of novel corona is reported in India on January 30, 2020. The growth in the initial phase is following exponential. In this study an attempt has been made to model the spread of novel corona infection. For this purpose logistic growth model with minor modification is used and the model is applied on truncated information on novel corona confirmed cases in India. The result is very exiting that till date predicted number of confirmed corona positive cases is very close to observed on. The time of point of inflexion is found in the end of the April, 2020 means after that the increasing growth will start decline and there will be no new case in India by the end of July, 2020.
The Utility of rRT-PCR in Diagnosis and Assessment of Case-fatality rates of COVID-19 In the Iranian Population – Positive Test Results are a Marker for Illness Severity
Authors: Janbabaei Ghasem , Brandt Eric J. , Golpira Reza , Raeisi Alireza , Tabrizi Jafar Sadegh , Safikhani Hamid Reza , Talebian Mohammad Taghi , Samiee Siamak Mirab , Biglar Alireza , Malekzadeh Reza , Mani Arya 
Published: May 2020

AbstractThe utility of PCR-based testing in characterizing patients with COVID-19 and the severity of their disease remains unknown. We performed an observational study among patients presenting to hospitals in Iran who were tested for 2019-nCoV viral RNA by rRT-PCR between the fourth week of February 2020 to the fourth week of March 2020. Frequency of symptoms, comorbidities, intubation, and mortality rates were compared between COVID-19 positive vs. negative patients. 96103 patients were tested from 879 hospitals. 18754 (19.5%) tested positive for COVID-19. Positive testing was more frequent in those 50 years or older. The prevalence of cough (54.5% vs. 49.7%), fever (49.5% vs. 44.7%), and respiratory distress (43.0% vs. 39.0%) but not hypoxia (46.9% vs. 56.7%) was higher in COVID-19 positive vs. negative patients (p<0.001 for all). More patients had cardiovascular diseases (10.6% vs. 9.5%, p<0.001) and type 2 diabetes mellitus (10.8% vs. 8.7%, p<0.001) among COVID-19 positive vs. negative patients. There were fewer patients with cancer (1.1%, vs. 1.4%, p<0.001), asthma (1.9% vs. 2.5%, p<0.001), or pregnant (0.4% vs. 0.6%, =0.001) in COVID-19 positive vs. negative groups. COVID-19 positive vs. negative patients required more intubation (7.7% vs. 5.2%, p<0.001) and had higher mortality (14.6% vs. 6.3%, p<0.001). Odds ratios for death of positive vs negative patients range from 2.01 to 3.10 across all age groups. In conclusion, COVID-19 test-positive vs. test-negative patients had more severe symptoms and comorbidities, required higher intubation, and had higher mortality. rRT-PCR positive result provided diagnosis and a marker of disease severity in Iranians.
Chloroquine Administration in Breastfeeding Mothers Associates with Increased HIV-1 Plasma Viral Loads
Authors: Paxton William A , Naarding Marloes A , Wit Ferdinand WNM , Veldhuijzen Nienke J , Chersich Matthew F , Kankindi Brigitte , Douma Rene A , Tuyizere Samuel , Jurriaans Suzanne , Sparidans Rolf W , Beijnen Jos H , Pollakis Georgios , Boelaert Johan R , Lange Joep MA , Vyankandondera Joseph , Luchters Stanley 
Published: May 2020

AbstractChloroquine (CQ) and Hydroxychloroquine (HCQ) have been proposed to be effective at treating COVID-19 patients. We, and others, have previously reported on the capacity of CQ to reduce HIV-1 replication in vitro. We tested CQ administration in post-partum mothers on influencing HIV-1 viral loads in human milk as a means of lowering mother to child transmission. A Phase I/II, randomized, placebo-controlled study to evaluate chloroquine administration to reduce HIV-1 RNA levels in human milk: the CHARGE study. Thirty HIV-1 positive pregnant Rwandese women (CQ n = 20; placebo n = 10) were enrolled in a 16-week study, with the treatment group receiving a 200 mg oral dose of CQ daily. Base-line plasma viral load (pVL) measurements and CD4 counts were determined prior to delivery, and pVL, breast milk VL (bmVL) and CQ levels measured during treatment. For women receiving treatment, CQ concentration was higher in breast milk compared to plasma (over 2.5-fold), with a positive correlation between the levels in the two compartments (P < 0.003). A link between high CQ concentrations in plasma and high CD4 counts (P < 0.001) was observed. Surprisingly, we found a significant increase in pVL after CQ treatment in over half of the mothers (n=11; P < 0.001) and with no alteration to bmVL measurements. No specific amino acid alterations in the gp120 envelope sequences could be associated with CQ administration. CQ usage is associated with a significant increase to pVL in early breastfeeding mothers from Rwanda which cautions against the use of CQ in such individuals. Our results highlight a discrepancy between CQ effects on modulating HIV-1 replication in vitro versus in vivo and indicate caution when prescribing CQ to postpartum HIV-1 untreated mothers. This discrepancy should be taken into consideration when testing CQ or HCQ treatment in COVID-19 clinical trials, especially relating to the post-partum setting.
Modeling COVID-19 on a network: super-spreaders, testing and containment
Authors: Reich Ofir , Shalev Guy , Kalvari Tom 
Published: May 2020

AbstractTo model COVID-19 spread, we use an SEIR agent-based model on a graph, which takes into account several important real-life attributes of COVID-19: super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to achieve suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals, equivalent in many models to R0, is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, our model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution. We provide mathematical arguments to argue that certain results of our simulations hold in more general settings.
A non-parametric mathematical model to investigate the dynamic of a pandemic
Authors: Sosa Robert , Sosa Wilfredo 
Published: May 2020

AbstractPopulations are diverse in size, capacity response, and measures to contain a pandemic such covid19. Then, it rises serious and critical questions to whether general measures can be taken worldwide. Also, it is unclear if conventional parametric methods are suitable to study pandemics since their dynamic is modulated by biological, economical, environmental, social, and cultural factors. In this manuscript, we apply a recently developed non-parametric mathematical method that comes from regional economy, to investigate the dynamic of a pandemic. We apply this novel methodology to study the ongoing covid19 pandemic in all USA states and in the country itself. The generality of our methodology makes it suitable to investigate also the worldwide dynamics of diseases such HIV or tuberculosis.
Prediction of the Epidemic Peak of Covid19 in Egypt, 2020
Authors: El Desouky Eman D. 
Published: May 2020

AbstractObjectivesSince December 2019 a pandemic of new novel coronavirus has started from Wuhan, China, in Egypt, the first case reported on February 14, 2020. In this study we aimed to predict the time of possible peak and simulate the changes could be happen by the social behavior of Egyptians during Ramadan (the holy month).MethodsSIR and SEIR compartmental models were used to predict the peak time. We simulated different expected scenarios based to examine their effects on the peak timing.ResultsWe found that the peak most likely to be in middle of June 2020. Simulating different transmission rate probability and R0 the earliest peak could to be in the May 20 and latest one could be in 18 July. The peak shifted much earlier to 11th April 2020 without lockdown and other mitigation strategies.ConclusionSocial behaviors of citizens during the holy month will dramatically affect the peak timing. Mitigations strategies and other lockdown measure helped to delay the expected peak.
Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer’s disease-like mutation inpsen1indicate effects on oxidative phosphorylation, mcm functions, and iron homeostasis
Authors: Dong Yang , Newman Morgan , Pederson Stephen , Hin Nhi , Lardelli Michael 
Published: May 2020

AbstractEarly-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation,psen1Q96_K97del, in zebrafish and performed a transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs. We generated clutches of wild type and heterozygouspsen1Q96_K97del7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed Goseq analysis and gene set enrichment analysis (GSEA). This predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygouspsen1Q96_K97delbrains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due toPSEN1mutation. The upregulation ofcrystallingene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Extracellular matrix (ECM) related genes were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3’ untranslated regions. These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygouspsen1Q96_K97delEOfAD-like mutant brains.
Closure motif-mediated state changes of the HORMA protein ASY1
Authors: Yang Chao , Hu Bingyan , Portheine Stephan Michael , Chuenban Pichaporn , Schnittger Arp 
Published: May 2020

AbstractMeiotic HORMA domain-containing proteins (HORMADs) are key components of the chromosome axis and play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for this step by promoting HORMAD oligomerization. In late prophase, ASY1 and its homologs are progressively removed from synapsed chromosomes promoting chromosome synapsis and recombination. The conserved AAA+ ATPase PCH2/TRIP13 has been intensively studied for its role in removing HORMADs from synapsed chromosomes. In contrast, not much is known about how HORMADs are loaded onto chromosomes. Here, we reveal that the PCH2-mediated dissociation of the HORMA domain of ASY1 from its closure motif is important for the nuclear targeting and subsequent chromosomal loading of ASY1. This indicates that the promotion of ASY1 to an ‘unlocked’ state is a prerequisite for its nuclear localization and chromosomal assembly. Likewise, we find that the closure motif is also necessary for the removal of ASY1 by PCH2 later in prophase. Our work results in a grand unified model for PCH2 and HORMADs function in meiosis.
Oncogenic GLI1 and STAT1/3 activation drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer cells
Authors: Elmer Dominik P. , Strobl Victoria , Stockmaier Georg , Dang Hieu-Hoa , Wiederstein Markus , Licha David , Strobl Anna , Sternberg Christina , Tesanovic Suzana , Grund-Groeschke Sandra , Gruber Wolfgang , Wolff Florian , Moriggl Richard , Risch Angela , Reischl Roland , Huber Christian G. , Horejs-Hoeck Jutta , Aberger Fritz 
Published: May 2020

AbstractPharmacological targeting of Hedgehog (HH)/GLI has proven effective for certain blood, brain and skin cancers including basal cell carcinoma (BCC). However, limited response rates and the development of drug resistance call for improved anti-HH therapies that take into account synergistic crosstalk mechanisms and immune evasion strategies.In previous work, we demonstrated that crosstalk of HH/GLI with pro-inflammatory Interleukin-6 (IL6) signaling drives BCC by promoting tumor cell proliferation [1]. In the present study, we screened for possible mechanisms of cancer immune evasion regulated by synergistic HH-IL6 signaling and identified the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) as a novel transcriptional target co-regulated by HH-IL6 signaling. Analysis of thecis-regulatory region of IDO1 by chromatin-immunoprecipitation revealed co-occupancy of this region by HH- IL6 induced GLI1 and STAT3 transcription factors along with active chromatin marks at the histone level. Elevated expression of IDO1 in human BCC with high-level HH and IL6 signatures supports the clinical relevance of our mechanistic data. Genetic inhibition of GLI1 expression prevented the induction of IDO1 expression in response to IL6/STAT3 and IFNγ/STAT1 signaling in human melanoma cells. Pharmacological targeting of HH signaling at the level of GLI proteins interfered with IDO1 expression and consequently prevented the production of the immunosuppressive metabolite kynurenine generated by active IDO1 from tryptophan. Further, inhibition of GLI1 enhanced the efficacy of the selective IDO1 inhibitor epacadostat. Of note, inhibition of HH/GLI signaling in melanoma cells not only reduced IDO1 expression but also interfered with the repression of T cell activation by attenuating IDO1/kynurenine-mediated immunosuppression. These data identify the immunosuppressive IDO1-kynurenine pathway as a novel pro-tumorigenic effector of oncogenic HH-IL6 and GLI-STAT cooperation. Our data suggest simultaneous pharmacological targeting of the HH/GLI, JAK/STAT and IDO1- kynurenine axis as rational combination therapy in skin cancers.
Mechanism and function of root circumnutation
Authors: Taylor Isaiah , Lehner Kevin , McCaskey Erin , Nirmal Niba , Ozkan-Aydin Yasemin , Murray-Cooper Mason , Jain Rashmi , Hawkes Elliot W. , Ronald Pamela C. , Goldman Daniel I. , Benfey Philip N. 
Published: May 2020

Abstract:Early root growth is critical for plant establishment and survival. We have identified a molecular pathway required for oscillatory root tip movement known as circumnutation. Here we report a multiscale investigation of the regulation and function of this phenomenon. We identify key cell signaling events comprising interaction of the ethylene, cytokinin, and auxin hormone signaling pathways. We identify the geneOryza sativa Histidine Kinase-1/OsHK1, as well as the auxin influx carrier geneOsAUX1, as essential regulators of this process in rice. Robophysical modelling demonstrated the benefits of tip movement for navigating past obstacles, prompting us to challenge mutant and wild-type plants with different substrates. Consistent with model behavior, root circumnutation facilitated exploration of a solid surface and promoted seedling establishment in rocky soil. Thus, the integration of robotics, physics and biology elucidated the functional importance of root circumnutation and uncovered the molecular mechanisms underlying its regulation.One sentence summaryCircumnutation facilitates root exploration.