bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markedly heterogeneous COVID-19 testing plans among US colleges and universities
Authors: Booeshaghi A. Sina , Tan Fayth , Renton Benjamin , Berger Zackary , Pachter Lior 
Published: August 2020

AbstractAs the COVID-19 pandemic worsens in the United States [1], colleges that have invited students back for the fall are finalizing mitigation plans to lessen the spread of SARS-CoV-2. Even though students have largely been away from campuses over the summer, several outbreaks associated with colleges have already occurred [2], foreshadowing the scale of infection that could result from hundreds of thousands of students returning to college towns and cities. While many institutions have released return-to-campus plans designed to reduce viral spread and to rapidly identify outbreaks should they occur, in many cases communications by college administrators have been opaque. To contribute to an evaluation of university preparedness for the COVID-19 pandemic, we assessed a crucial element: COVID-19 on-campus testing. We examined testing plans at more than 500 colleges and universities throughout the US, and collated statistics, as well as narratives from publicly facing websites. We discovered a highly variable and muddled state of COVID-19 testing plans among US institutions of higher education that has been shaped by discrepancies between scientific studies and federal guidelines. We highlight cases of divergence between university testing plans and public health best practices, as well as potential bioethical issues.
The clinical spectrum of COVID-19: A population-based cohort study in Iceland
Authors: Eythorsson Elias , Helgason Dadi , Ingvarsson Ragnar Freyr , Bjornsson Helgi K , Olafsdottir Lovisa Bjork , Bjarnadottir Valgerdur , Runolfsdottir Hrafnhildur Linnet , Bjarnadottir Solveig , Agustsson Arnar Snaer , Oskarsdottir Kristin , Thorvaldsson Hrafn Hliddal , Kristjansdottir Gudrun , Armannsdottir Brynja , Bjarnason Agnar , Johannsson Birgir , Gudlaugsson Olafur , Gottfredsson Magnus , Sigurdsson Martin I , Indridason Olafur S , Palsson Runolfur 
Published: August 2020

AbstractBackgroundPrevious studies on the epidemiology and clinical characteristics of COVID-19 have generally been limited to hospitalized patients. The aim of this study was to describe the complete clinical spectrum of COVID-19, based on a nationwide cohort with extensive diagnostic testing and a rigorous contact tracing approach.MethodsA population-based cohort study examining symptom progression using prospectively recorded data on all individuals with a positive test (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who were enrolled in a telehealth monitoring service provided to all identified cases in Iceland. Symptoms were systematically monitored from diagnosis to recovery.ResultsFrom January 31 to April 30, 2020, a total of 45,105 individuals (12% of the Icelandic population) were tested for SARS-CoV-2, of whom 1797 were positive, yielding a population incidence of 5 per 1000 individuals. The most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 5.3% of cases reported no symptoms and 3.1% remained asymptomatic during follow-up. In addition, 216 patients (13.8%) and 349 patients (22.3%) did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. The majority (67.5%) of patients had mild symptoms throughout the course of the disease.ConclusionIn the setting of broad access to diagnostic testing, the majority of SARSCoV-2-positive patients were found to have mild symptoms. Fever and dyspnea were less common than previously reported. A substantial proportion of patients did not meet recommended case definitions at the time of diagnosis.Key pointsQuestionWhat is the frequency and progression of various symptoms experienced by patients with COVID-19?FindingsIn this population-based cohort study that included all SARS-CoV-2-positive patients in Iceland, most patients (67.5%) had mild symptoms throughout their disease course. At the time of diagnosis, 5.3% were asymptomatic, of whom roughly half developed symptoms during follow-up. Common presenting symptoms included myalgia (55%), headache (51%), and non-productive cough (49%). At diagnosis, 13.8% and 22.3% did not meet the Centers for Disease Control and Prevention and World Health Organization case definitions for suspected COVID-19, respectively.MeaningIn the setting of broad access to diagnostic testing, the majority of SARSCoV-2-positive patients were found to have mild symptoms and almost one-fifth did not meet published clinical criteria for RT-PCR testing.
Alcohol boosts pheromone production in male flies and makes them sexier
Authors: Keesey Ian W. , Doll Georg , Chakraborty Sudeshna Das , Baschwitz Amelie , Lemoine Marion , Kaltenpoth Martin , Svatoš Aleš , Sachse Silke , Knaden Markus , Hansson Bill S. 
Published: August 2020

The attraction ofDrosophila melanogastertowards byproducts of alcoholic fermentation, especially ethanol, has been extensively studied1–4. However, the adaptive value of this behavior has not been elucidated. Previous studies have suggested anthropomorphic interpretations ofD. melanogasterbehavior towards alcohols5,6. Here, we instead assert that there exists a simple yet vital biological rationale for alcohol contact and consumption by these insects. We show that exposure to alcohols, especially methanol, results in an immediate amplification of fatty acid ester pheromone levels, which in turn elevates the probability that a male will successfully compete for a female during courtship. We proceed to identify three types of olfactory sensory neurons that detect ethanol and methanol. Moreover, we trace the ensuing neural circuits and reveal their role in controlling both attraction and aversion, where valence is balanced around mating status. Based on our results, we deduce that male flies associate with sources of alcohol as a biological imperative related to reproduction, and we provide an assessment of how and whyD. melanogasteris associated with alcohol using a sound ecological and natural history approach to this previously enigmatic biological phenomenon.One sentence summaryFlies gain pheromone and courtship advantages with alcohol, but methanol is toxic, thus flies must balance risk versus reward.
Characterisation of 22446 patients attending UK emergency departments with suspected COVID-19 infection: Observational cohort study
Authors:   The PRIEST Research Group (details in Appendix 1), Goodacre Steve , Thomas Ben , Lee Ellen , Sutton Laura , Loban Amanda , Waterhouse Simon , Simmonds Richard , Biggs Katie , Marincowitz Carl , Schutter Jose , Connelly Sarah , Sheldon Elena , Hall Jamie , Young Emma , Bentley Andrew , Challen Kirsty , Fitzimmons Chris , Harris Tim , Lecky Fiona , Lee Andrew , Maconochie Ian , Walter Darren 
Published: August 2020

ABSTRACTBackgroundHospital emergency departments play a crucial role in the Initial management of suspected COVID-19 infection. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results.MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22446 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days.ResultsAdults were acutely unwell (median NEWS2 score 4) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.9%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Adult men and women presented in similar numbers (10210 versus 10506), but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.7% v 13.3%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to be admitted (60.8%, 57.3%, 69.6%) or die (11.9%, 11.2%, 16.8%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with confirmed COVID-19 had similar age and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.7% v 15.9%).ConclusionsImportant differences exist between patient groups presenting to the emergency department with suspected COVID-19. People with confirmed COVID-19 have a poor prognosis, compared with similar emergency admissions without confirmed COVID-19.RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533
Contextualising Single-Arm Ophthalmology Trials With Real-World Data: An Emulated Target Trial Comparing The Efficacy of Interventions For Neovascular Age-Related Macular Degeneration
Authors: Thomas Darren S. , Lee Aaron Y. , Müller Philipp L. , Schwartz Roy , Olvera-Barrios Abraham , Warwick Alasdair N. , Patel Praveen J. , Heeren Tjebo F.C. , Egan Catherine , Taylor Paul , Tufail Adnan 
Published: August 2020

ABSTRACTMethods of causal inference have shown promise in replicating randomised trials using real-world data recorded by Electronic Health Records (EHRs). We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week-54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n 65) was taken from the ABC randomised controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from EHRs and synthetic control arms were created by emulating randomisation conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ −15 Early Treatment Diabetic Retinopathy Letters (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ −15 ETDRS letters by week 54. Our findings suggest off-label bevacizumab to be neither non-inferior nor superior to licensed aflibercept. While being no substitute for randomised controlled trials, emulated target trials could aid the interpretation of single-armed trials.
Mass molecular testing for COVID19 using NGS-based technology and a highly scalable workflow
Authors: de Mello Malta Fernanda , Amgarten Deyvid , Val Felipe Camilo , Santana Rubia Anita Ferraz , Cervato Murilo Castro , de Azevedo Bruna Mascaro Cordeiro , de Souza Basqueira Marcela , Alves Camila Oliveira dos Santos , Nobrega Maria Soares , Pinho João Renato Rebello 
Published: August 2020

ABSTRACTSince first reported case of the new coronavirus infection in Wuhan, China, researchers and governments have witnessed an unseen rise in the number of cases. Thanks to the rapid work of Chinese scientists, the pathogen now called SARS-CoV-2 has been identified and its whole genome has been deposited in public databases by early January 2020. The availability of the genome has allowed researchers to develop Reverse Transcription - Polymerase Chain Reaction (RT-PCR) assays, which are now the gold-standard for molecular diagnosis of the respiratory syndrome COVID19. Because of the rising number of cases and rapid spreading, the world has been facing a shortage of RT-PCR supplies, especially the ones involved in RNA extraction. This has been a major bottleneck to increase testing capacity in many countries that do not significantly manufacture these supplies (Brazil included). Additionally, RT-PCR scalability is highly dependent on equipment that usually perform testing of 96 samples at a time. In this work, we describe a cost-effective molecular NGS-based test for diagnosis of COVID19, which uses a single-step RNA extraction and presents high scalability and accuracy when compared to the gold-standard RT-PCR. A single run of the NGS-based test using the Illumina NextSeq 550 mid-end sequencing equipment is able to multiplex 1,536 patient’s samples, providing individual semi-qualitative results (detected, not detected). Detected results are provided with fragments per million (FPM) values, which was demonstrated to correlate with RT-PCR Cycle Threshold (CT) values. Besides, usage of the high-end Illumina Novaseq platform may yield diagnostic for up to 6,144 samples in a single run. Performance results when compared with RT-PCR show general accuracy of 96% (or 98% when only samples with CT values for gene N lower than 30 are considered). We have also developed an online platform, called VarsVID®, a Varstation® feature, to help test executors to easily scale testing numbers. Sample registering, wet-lab worksheets, sample sheet for sequencing and results’ display are all features provided by VarsVID® on Varstation®. Altogether, these results will contribute to control COVID19 pandemics.
Application of a generalized SEIR model for covid-19 in Algeria
Authors: Lounis Mohamed , Azevedo Juarez dos Santos 
Published: August 2020

AbstractThe novel coronavirus diseases 2019 (COVID-19) in Wuhan is continuing to impress the world by its fast spread and the number of affected persons attracting an unprecedented attention. In this article, we used the classical SEIR model and a generalized SEIR model called SEIRDP model inspired in a model previously used during the outbreak in China to predict the evolution of COVID-19 in Algeria for a future period of 100 days using official reported data from early April to early August, 2020. Initial evaluation showed that thetwo models had a net correspondence with the reported data during this period for cumulative infected cases but the number of cumulative deaths was underestimated with the classical SEIR model. Model prediction with the SEIRDP concluded that the number of cumulative infected cases will increase in the next days reaching a number of about 60 k in middle November with a median of about 300 daily cases. Also, the number of estimated deaths will be around 2k. These results suggest that the COVID-19 is ongoing to infect more persons which may push national authorities to carefully act in the probable leaving of containment.
Effective reproduction number for COVID-19 in Aotearoa New Zealand
Authors: Binny Rachelle N. , Lustig Audrey , Brower Ann , Hendy Shaun C. , James Alex , Parry Matthew , Plank Michael J. , Steyn Nicholas 
Published: August 2020

AbstractThe effective reproduction number, Reff, is the average number of secondary cases infected by a primary case, a key measure of the transmission potential for a disease. Compared to many countries, New Zealand has had relatively few COVID-19 cases, many of which were caused by infections acquired overseas. This makes it difficult to use standard methods to estimate Reff. In this work, we use a stochastic model to simulate COVID-19 spread in New Zealand and report the values of Reff from simulations that gave best fit to case data. We estimate that New Zealand had an effective reproduction number Reff = 1.8 for COVID-19 transmission prior to moving into Alert Level 4 on March 25 2020 and that after moving into Alert level 4 this was reduced to Reff = 0.35. Our estimate Reff = 1.8 for reproduction number before Alert Level 4, is relatively low compared to other countries. This could be due, in part, to measures put in place in early-to mid-March, including: the cancellation of mass gatherings, the isolation of international arrivals, and employees being encouraged to work from home.
Hypersensitivity reactions to IL-1 and IL-6 inhibitors are linked to common HLA-DRB1*15 alleles
Authors: Hollenbach Jill , Ombrello Michael J. , Tremoulet Adriana , Duque Jaime S. Rosa , Chua Gilbert T. , Montero-Martin Gonzalo , Burns Jane C. , Shimizu Chisato , Deutsch Gail , Monos Dimitri , Mallajosyula Vamsee , Xu Jianpeng , Ghosh Debopam , Tan Serena , Remmers Elaine , Canna Scott , Szymanski Ann Marie , Rubin Danielle , Fernandez-Vina Marcelo A. , Saper Vivian E. , Mellins Elizabeth D. ,   Drug Hypersensitivity in sJIA Consortium investigators
Published: August 2020

ABSTRACTIn Saper et al (2019), we described systemic JIA patients who developed a high-fatality diffuse lung disease (DLD) while on IL-1 or IL-6 inhibitors. We observed severe delayed drug hypersensitivity reactions (DHR) in a significant subset. Because alleles of the human leukocyte antigen (HLA) loci can mediate DHR, we investigated HLA genotype association with these DHR. We typed subjects treated with these inhibitors: 34 sJIA/DHR/DLD, 11 sJIA/DHR without DLD, 18 drug-tolerant sJIA, and 19 Kawasaki disease (KD) patients in an anti-IL-1(anakinra) trial. We also accessed genotypes from a large sJIA case/control cohort.We first compared White subjects with sJIA/DHR to 550 ancestry-matched sJIA subjects. We found striking enrichments of HLA-DRB1*15:01, HLA-DQA1*01:02, and DQB1*06:02, alleles in near-complete linkage (White individuals). HLA-DRB 1*15:01 (as haplotype proxy) was increased in White sJIA subjects with DHR/DLD versus sJIA drug-tolerant controls and was observed upon inclusion of sJIA+DHR-only and KD+DHR White subjects. In our entire cohort regardless of ancestry, 75% carried HLA-DRB 1*15:01 or the structurally related DRB1*15:03 and DRB1*15:06, which were absent among drug-tolerant subjects (p=5 x 10-13; Odds Ratio lower bound=20.11).Patients who harbor HLA-DRB1*15 alleles are at high risk of developing DHR to anti-IL-1/IL-6. Our data also suggest DHR maybe a trigger/enhancer of DLD in sJIA patients and support performing prospective HLA screening in sJIA, its adult-onset counterpart, and other inflammatory conditions where these drugs are used, such as KD.
A system-level gene regulatory network model forPlasmodium falciparum
Authors: Neal ML , Wei L , Peterson E , Arrieta-Ortiz ML , Danziger SA , Baliga NS , Kaushansky A , Aitchison JD 
Published: August 2020

AbstractMany of the gene regulatory processes ofPlasmodium falciparum, the deadliest malaria parasite, remain poorly understood. To develop a comprehensive guide for exploring this organism’s gene regulatory network, we generated a system-level model ofPlasmodium falciparumgene regulation using a well-validated, machine-learning approach for predicting interactions between transcription regulators and their targets. The resulting network accurately predicts expression levels of transcriptionally coherent gene regulatory programs in independent transcriptomic data sets from parasites collected by different research groups in diverse laboratory and field settings. Thus, our results indicate that our gene regulatory model has predictive power and utility as a hypothesis-generating tool for illuminating clinically relevant gene regulatory mechanisms withinPlasmodium falciparum. Using the set of regulatory programs we identified, we also investigated correlates of artemisinin resistance based on gene expression coherence. We report that resistance is associated with incoherent expression across many regulatory programs, including those controlling genes associated with erythrocyte-host engagement. These results suggest that parasite populations with reduced artemisinin sensitivity are more transcriptionally heterogenous. This pattern is consistent with a model where the parasite utilizes bet-hedging strategies to diversify the population, rendering a subpopulation more able to navigate drug treatment.
Decision Support Systems based on Scientific Evidence: Bibliometric Networks of InvasiveLantana camara
Authors: Mishra Preet , Prasad Abhishek , Babu Suresh , Yadav Gitanjali 
Published: August 2020

ABSTRACTExtraction and analysis of useful knowledge from the vast amount of relevant published literature can add valuable insights to any research theme or area of interest. We introduce a simplified bibliometric data analysis protocol for gaining substantial insights into research thematics, which can also serve as a handy practical skill for researchers, while working from home. In this paper, we provide ways of developing a holistic research strategy using bibliometric-data driven approaches that integrate network analysis and information management, without the need of full paper access. This protocol is a comprehensive multi-modular pathway for analysis of metadata obtained from major scientific publishing houses by use of a Decision Support System (DSS). A simple case study on the invasive speciesLantana camarahas been presented as a proof-of-concept to show how one can implement this DSS based protocol. Some perspectives are also provided on how the outcomes can be used directly or scaled up for long term research interventions. We hope that this work will simplify exploratory literature review, and enable rational design of research objectives for scholars, as well as development of comprehensive grant proposals that address gaps in research.
TRPV2 interaction with small molecules and lipids revealed by cryo-EM
Authors: Protopopova Anna D. , Pumroy Ruth A. , de la Roche Jeanne , Haug Ferdinand M. , Sousa Bárbara B. , Gallo Pamela N. , Bernardes Gonçalo J.L. , Leffler Andreas , Moiseenkova-Bell Vera Y. 
Published: August 2020

AbstractTransient receptor potential vanilloid 2 (TRPV2) plays a critical role in a variety of physiological and pathophysiological processes, putting TRPV2 on the list of important drug targets. Yet, specific TRPV2 agonists and antagonists are currently unavailable. Their development requires a precise knowledge of how the currently known non-specific small molecules interact with TRPV2 at the molecular level. Here we present TRPV2 structures in ligand-bound states resolved by cryo-electron microscopy in the presence of 2-aminoethoxydiphenyl borate (2-ABP), 2-APB with doxorubicin (DOXO), and ruthenium red (RR). We identified a novel 2-APB drug binding site between the S5 helix and S4-S5 linker on two adjacent TRPV2 monomers and determined the mechanism of TRPV2 pore block by RR. We also showed that a large organic molecule like DOXO can enter the TRPV2 pore in the presence of 2-APB. Additionally, we discovered a structural lipid bound in a unique position in the “vanilloid pocket”, which is absent in the 2-APB-bound state of the channel, allowing us to propose a model for TRPV2 channel gating. Together, this work provides a further understanding of TRPV2 function and a structural framework for the development of TRPV2-specific modulators.