bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical Model to Study Early COVID-19 Transmission Dynamics in Sri Lanka
Authors: Perera Sanjeewa Nishantha , Ganegoda Naleen C , Siriwardhana Dhammika Deepani , Weerasinghe Manuj C 
Published: May 2020

AbstractBackgroundWorld Health Organization declared COVID-19 as a pandemic on 11th March. Sri Lanka is currently experiencing a cluster epidemic with a specific group of overseas returnees and their contacts. The objective of this study was to develop a mathematical model to predict the epidemic in Sri Lanka incorporating measures taken for social distancing and prevention of social gatherings.MethodsA hybrid model incorporating both exponential and polynomial features was developed and parameters were estimated. The developed model was validated using the datasets of three reference countries. Finally, the model was applied to the Sri Lankan data to simulate the epidemic behaviour. Additional features were incorporated to the model to examine the effects of current control measures.FindingsSri Lanka will have a peak of 177 COVID-19 active cases at the end of second incubation period from the index case of our projection, if the same trend continues. At 10% risk, we project a peak of 263 COVID-19 active cases at the end of third incubation period, and a peak of 353 at the end of fourth incubation period. Should the risk level reach 20%, the peak will be above 1000 active cases after 90 days. Simulations incorporating control measures predict that, deviation from the control measures currently in place could trigger exponential behaviour of the epidemic.InterpretationThe hybrid model combining exponential and polynomial functions showed promising results to predict COVID-19 epidemic. Projections indicate that any early relaxation of control measures is not advisable. This methodological approach can be replicated in other settings at the initial stages of the epidemic.
Comparison of the Clinical Implications among Two Different Nutritional Indices in Hospitalized Patients with COVID-19
Authors: Du Xuebei , Liu Yuwei , Chen Jing , Peng Li , Jin Yalei , Cheng Zhenshun , Wang Harry H.X. , Luo Mingqi , Chen Ling , Zhao Yan 
Published: May 2020

SummaryBackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID-19.MethodsIn this retrospective single-center study, we finally included 245 consecutive patients who confirmed COVID-19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death.Results212 of them were discharged and 33 of them died. In-hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe-CONUT group than in the moderate-, mild-, and normal-CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124–10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI (0.581–0.896), P=0.003) were independent predictors of all-cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in-hospital death(odds ratio 24.225, 95% CI(2.147–273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI (0.644–0.862); respectively). The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI (0.686–0.809); respectively). We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID-19patients.ConclusionThe CONUT score and PNI could be a reliable prognostic marker of all-cause deathin patients with COVID-19.
COVID-19 and Inflammatory Bowel Diseases: risk assessment, shared molecular pathways and therapeutic challenges
Authors: Popa Iolanda Valentina , Diculescu Mircea , Mihai Cătălina , Cijevschi-Prelipcean Cristina , Burlacu Alexandru 
Published: May 2020

AbstractBackgroundThe novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with serious threats to public health. In this paper, we aimed to review the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. Also, we focused on several molecular insights that could explain why IBD patients appear to not have higher risks of infection and worse outcome in COVID-19 than the general population, in attempt to provide scientific support for safer decisions in IBD patient care.MethodsPubMed electronic database was interogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV and inflammatory bowel diseases. In addition, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19).DiscussionsFew molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L alternate receptor and phosphorylated α subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny including “cytokine storm” prevention and treatment, immunomodulation, interferon signaling blocking, viral endocytosis inhibition.ConclusionsUsing current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility and treatment management of SARS-CoV-2 infection in IBD must be further explored.
Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes
Authors: Crisan-Dabija Radu , Grigorescu Cristina , Pavel Cristina-Alice , Artene Bogdan , Popa Iolanda Valentina , Cernomaz Andrei , Burlacu Alexandru 
Published: May 2020

AbstractBackgroundThe threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies.Methods and ResultsPubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID19? How does one diagnosis affect the other?DiscussionsFew essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection.ConclusionsBecause viral respiratory infections and TB impede the host’s immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.
A comparison of health care worker-collected foam and polyester nasal swabs in convalescent COVID-19 patients
Authors: Hart Brian , Tu Yuan-Po , Jennings Rachel , Verma Prateek , Padgett Leah R , Rains Douglas , Vojta Deneen , Berke Ethan M 
Published: May 2020

ABSTRACTBackgroundThe exponential growth of COVID-19 cases and testing has created supply shortages at various points in the testing workflow. As of April 15, 2020 FDA recommendations only allowed for the use of nasopharyngeal, flocked mid turbinate, or foam nasal swabs, all of which are in very low supply. Polyester swabs are more readily available and mass producible. We compare the performance of polyester and foam swabs stored in different transport media.MethodsBoth polyester and foam nasal swabs were collected from convalescent COVID-19 patients at a single visit. Using the foam nasal swabs as the comparator, sensitivity of the polyester swabs in each media were calculated, three by three tables were constructed to measure concordance, and cycle threshold (Ct) values were compared.Findings126 visits had polyester and foam swabs stored in viral transport media (VTM), 51 had polyester and foam swabs stored in saline, and 63 had a foam swab in VTM and a polyester swab stored in a dry tube. Using nasal foam swabs as a comparator, polyester nasal swabs had a sensitivity of 86·5% when both samples were stored in VTM, 86·7% when both samples were stored in saline, and 72·4% when the polyester swab was stored dry and the foam swab was stored in VTM. Polyester and foam Ct values from the same visit were correlated, but polyester swabs showed decreased performance for cases with a viral load near the detection threshold and higher Ct values on average.InterpretationPolyester nasal swabs showed a reduction in performance from foam nasal swabs, but may still provide a viable sample collection method given the current supply shortages and public health emergency.FundingLaboratory testing was conducted with financial support from Thermo Fisher Scientific.
Unannotated small RNA clusters in circulating extracellular vesicles detect early stage liver cancer
Authors: von Felden Johann , Garcia-Lezana Teresa , Dogra Navneet , Kozlova Edgar , Ahsen Mehmet Eren , Craig Amanda J. , Gifford Stacey , Wunsch Benjamin , Smith Joshua T. , Kim Sungcheol , Diaz Jennifer E. L. , Chen Xintong , Labgaa Ismail , Haber Philipp K. , Olsen Reena , Han Dan , Restrepo Paula , D’Avola Delia , Hernandez-Meza Gabriela , Allette Kimaada , Sebra Robert , Saberi Behnam , Tabrizian Parissa , Asgharpour Amon , Dieterich Douglas , Llovet Josep M , Cordon-Cardo Carlos , Tewari Ash , Schwartz Myron , Stolovitzky Gustavo , Losic Bojan , Villanueva Augusto 
Published: May 2020

ABSTRACTBackgroundHepatocellular carcinoma (HCC) is among the deadliest malignancies and surveillance tools for early detection are suboptimal. Extracellular vesicles (EVs) have gained increasing scientific interest due to their involvement in tumor initiation and metastasis, however, most extracellular RNA (exRNA) biomarker studies are limited to annotated genomic regions.MethodsEVs were isolated with ultracentrifugation and nanoDLD and quality assessed by electron microscopy, immunoblotting, nanoparticle tracking, and deconvolution analysis. We performed genome-wide small exRNA sequencing, including unannotated transcripts. We identified small RNA clusters (smRCs) and delineated their key genomic features across biospecimens (blood, urine, tissue) and EV isolation techniques. A 3-smRC signature for early HCC detection was trained and validated in two independent cohorts.ResultsEV-derived smRCs were dominated by uncharacterized, unannotated small RNA and uniformly tiled across the genome with a consensus sequence of 20bp. A 3-smRC signature was significantly overexpressed in circulating EVs of HCC patients compared to controls at risk or patients with non-HCC malignancies (p<0.01, n=157). An independent validation in a phase 2 biomarker study revealed 86% sensitivity and 91% specificity for the detection of early HCC from controls at risk (i.e. cirrhosis or chronic liver disease, n=209) (positive predictive value (PPV): 89%, area under the ROC curve [AUC]: 0.87). The 3-smRC signature was independent of alpha-fetoprotein (p<0.0001) and a composite model yielded an increased AUC of 0.93 (sensitivity: 85%, specificity: 94%, PPV: 95%).ConclusionAn exRNA-based 3-smRC signature from plasma detects early stage HCC, which directly leads to the prospect of a minimally-invasive, blood-only, operator-independent surveillance biomarker.One sentence summaryWe employ a novel, data-driven approach to identify and characterize small RNA clusters from unannotated loci in extracellular vesicle-derived RNA across different cancer types, isolation techniques, and biofluids, facilitating discovery of a robust biomarker for detection of early stage liver cancer.
Lab-Based and Self-Reported Indices of Fitness Show Lowered Fitness and Insight into Fitness in Individuals at Clinical High Risk for Psychosis
Authors: Damme Katherine S. F. , Sloan Richard P. , Bartels Matthew N. , Ozsan Alara , Ospina Luz H. , Kimhy David , Mittal Vijay A. 
Published: May 2020

AbstractIntroductionExercise is a promising intervention for clinical high-risk for psychosis (CHR) populations, who have attenuated positive symptoms, but evidence suggests that these youth may require tailored exercise interventions. Presently, the scope of the problem is unknown, as these youth may not be reliable reporters on fitness. This issue is compounded by the fact that there have been no investigations that utilized a formal fitness assessment in this critical population. The present study aims to determine the level of fitness in CHR youth with lab-based measures, test how effectively self-report measures characterize objective fitness indices, and explore clinical factors that may be interrupting reliable self-report-an important tool if these interventions are to be taken to scale.MethodsForty CHR individuals completed an exercise survey and lab-based indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed lab indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness.ResultsCHR youth showed greater BMI and lower VO2max compared to healthy volunteers. In the CHR group, abstract self-report items (perceived fitness) did not reflect lab indices of fitness, whereas specific exercise behaviors (intensity of exercise) showed stronger correlations with laboratory-based fitness measurements. Exploratory analyses suggested that positive symptoms involving grandiosity, and negative symptoms such as avolition, correlated with discrepancy between self-perception and laboratory findings of fitness.DiscussionResults suggest that CHR individuals are less objectively fit than matched controls, and that it will be important to consider unique population characteristics when weighing self-report data.
tRNA Biogenesis and Specific Aminoacyl-tRNA Synthetases Regulate Senescence Stability Under the Control of mTOR
Authors: Guillon Jordan , Toutain Bertrand , Petit Coralie , Coquelet Hugo , Henry Cécile , Boissard Alice , Guette Catherine , Coqueret Olivier 
Published: May 2020

ABSTRACTOncogenes or chemotherapy treatments trigger the induction of suppressive pathways such as apoptosis or senescence. Senescence was initially defined as a definitive arrest of cell proliferation but recent results have shown that this mechanism is also associated with cancer progression and chemotherapy resistance. Senescence is therefore much more heterogeneous than initially thought. How this response varies is not really understood, it has been proposed that its outcome relies on the secretome of senescent cells and on the maintenance of their epigenetic marks.Using experimental models of senescence escape, we now described that the stability of this suppression relies on specific tRNAs and aminoacyl-tRNA synthetases. Following chemotherapy treatment, the DNA binding of the type III RNA polymerase was reduced to prevent tRNA transcription and induce a complete cell cycle arrest. By contrast, during senescence escape, specific tRNAs such as tRNA-Leu-CAA and tRNA-Tyr-GTA were up-regulated. Reducing tRNA transcription appears necessary to control the strength of senescence since RNA pol III inhibition through BRF1 depletion maintained senescence and blocked cell persistence. mTOR inhibition also prevented CIS escape in association with a reduction of tRNA-Leu-CAA and tRNA-Tyr-GTA expression. Further confirming the role of the tRNA-Leu-CAA and tRNA-Tyr-GTA, their corresponding tRNA ligases, YARS and LARS, were necessary for senescence escape. This effect was specific since the CARS ligase had no effect on persistence. YARS and LARS inactivation reduced cell emergence and proteomic analysis indicated that this effect was associated with the down-regulation of E2F1 target genes.Overall, these findings highlight a new regulation of tRNA biology during senescence and suggest that specific tRNAs and ligases contribute to the strength and heterogeneity of this suppression.
Short-term responses to ocean acidification: effects on relative abundance of eukaryotic plankton from the tropical Timor Sea
Authors: Rahlff Janina , Khodami Sahar , Voskuhl Lisa , Humphreys Matthew P. , Stolle Christian , Arbizu Pedro Martinez , Wurl Oliver , Ribas-Ribas Mariana 
Published: May 2020

ABSTRACTAnthropogenic carbon dioxide (CO2) emissions drive climate change and pose one of the major challenges of our century. The effects of increased CO2in the form of ocean acidification (OA) on the communities of marine planktonic eukaryotes in tropical regions such as the Timor Sea are barely understood. Here, we show the effects of high CO2(pCO2=1823±161 μatm, pHT=7.46±0.05) versusin situCO2(pCO2=504±42 μatm, pHT=7.95±0.04) seawater on the community composition of marine planktonic eukaryotes immediately and after 48 hours of treatment exposure in a shipboard microcosm experiment. Illumina sequencing of the V9 hypervariable region of 18S rRNA (gene) was used to study the eukaryotic community composition. Down-regulation of extracellular carbonic anhydrase occurred faster in the high CO2treatment. Increased CO2significantly suppressed the relative abundances of different eukaryotic operational taxonomic units (OTUs), including important primary producers. These effects were consistent between abundant (DNA-based) and active (cDNA-based) taxa after 48 hours, e.g., for the diatomsTrieres chinensisandStephanopyxis turris. Effects were also very species-specific among different diatoms. Planktonic eukaryotes showed adaptation to the CO2treatment over time, but many OTUs were adversely affected by decreasing pH. OA effects might fundamentally impact the base of marine biodiversity, suggesting profound outcomes for food web functioning in the future ocean.
Poly(2-oxazoline) nanoparticle delivery enhances the therapeutic potential of vismodegib for medulloblastoma by improving CNS pharmacokinetics and reducing systemic toxicity
Authors: Hwang Duhyeong , Dismuke Taylor , Tikunov Andrey , Rosen Elias P. , Kagel John R. , Ramsey Jacob D. , Lim Chaemin , Zamboni William , Kabanov Alexander V. , Gershon Timothy R. , Sokolsky-Papkov Marina 
Published: May 2020

AbstractWe report a novel, nanoparticle formulation of the SHH pathway inhibitor vismodegib that improves efficacy for medulloblastoma treatment while reducing toxicity. Systemic therapies for brain tumors are complicated by restricted blood-brain barrier (BBB) permeability and dose-limiting extraneural toxicity, therefore improved delivery approached are needed. Here we show how a nanoparticle delivery system addresses these obstacles, bringing new efficacy to previously ineffective therapy. Vismodegib has been a promising agent for patients with SHH- subgroup medulloblastoma and is FDA-approved for basal cell carcinoma. However, vismodegib has limited benefit for patients with SHH-driven medulloblastoma, due to off-target toxicities and the development of resistance during therapy. We encapsulated vismodegib in polyoxazoline block copolymer micelles (POx-vismo). We then evaluated POx-vismo using transgenic mice engineered to develop endogenous medulloblastomas, testing the novel agent in a preclinical model with native vasculature and tumor microenvironment. POx-vismo showed improved CNS pharmacokinetics and reduced systemic and bone toxicity. Mechanistic studies show that POx nanoparticles did not enter the CNS, but rather acted within the vascular compartment to improve drug delivery by decreasing drug binding to serum proteins and reducing the volume of distribution. POx-vismo demonstrated improved efficacy, extending the survival of medulloblastoma-bearing mice. Our results show the potential for a simple, non-targeted nanoparticle formulation to improve systemic brain tumor therapy, and specifically to enhance vismodegib therapy for SHH-driven cancers.
SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms
Authors: Resende Paola Cristina , Motta Fernando Couto , Roy Sunando , Appolinario Luciana , Fabri Allison , Xavier Joilson , Harris Kathryn , Matos Aline Rocha , Caetano Braulia , Orgeswalska Maria , Miranda Milene , Garcia Cristiana , Abreu André , Williams Rachel , Breuer Judith , Siqueira Marilda M 
Published: May 2020

SummaryGenomic surveillance has become a useful tool for better understanding virus pathogenicity, origin and spread. Obtaining accurately assembled, complete viral genomes directly from clinical samples is still a challenging. Here, we describe three protocols using a unique primer set designed to recover long reads of SARS-CoV-2 directly from total RNA extracted from clinical samples. This protocol is useful, accessible and adaptable to laboratories with varying resources and access to distinct sequencing methods: Nanopore, Illumina and/or Sanger.