bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Droplet Digital PCR Assay to Detect SARS-CoV-2 RNA
Authors: Romeo Martin J. , DiPaola Christian P. , Mentus Cassidy , Timmers Cynthia D. 
Published: May 2020

AbstractWe describe a quantitative droplet digital PCR (ddPCR) assay for detection of SARS-CoV-2 viral ribonucleic acid (RNA) in total RNA extracted from human sputum. This method was validated using the guidance of the United States Food and Drug Administration’s Accelerated Emergency Use Authorization (EUA) Template for SARS-CoV-2 that Causes Coronavirus Disease (COVID-19) Molecular Testing of Respiratory Speciment in CLIA Certified High-Complexity Laboratories. Though our laboratory is not CLIA certified, this method met all criteria specified by the guidance document with a Limit of Detection (LOD) of 0.25 copies/μL in the final ddPCR (at least 19/20 replicates reactive), which we consider to be a Lower Limit of Quantification (LLOQ); inclusivity of all known annotated SARS-CoV-2 genomes; no cross-reactivity with other respiratory pathogens; and reactivity of all contrived positives at or above the LOD.
Understanding the nature of face processing in early autism: A prospective study
Authors: Tye Charlotte , Bussu Giorgia , Gliga Teodora , Elsabbagh Mayada , Pasco Greg , Johnsen Kristinn , Charman Tony , Jones Emily J.H. , Buitelaar Jan , Johnson Mark H. ,   the BASIS team
Published: May 2020

AbstractDimensional approaches to psychopathology interrogate the core neurocognitive domains interacting at the individual level to shape diagnostic symptoms. Embedding this approach in prospective longitudinal studies could transform our understanding of the mechanisms underlying neurodevelopmental disorders. Such designs require us to move beyond traditional group comparisons and determine which domain-specific atypicalities apply at the level of the individual, and whether they vary across distinct phenotypic subgroups. As a proof of principle, this study examines how the domain of face processing contributes to a clinical diagnosis of Autism Spectrum Disorder (ASD). We used an event-related potentials (ERPs) task in a cohort of 8-month-old infants with (n=148) and without (n=68) an older sibling with ASD, and combined traditional case-control comparisons with machine-learning techniques like supervised classification for prediction of clinical outcome at 36 months and Bayesian hierarchical clustering for stratification into subgroups. Our findings converge to indicate that a broad profile of alterations in the time-course of neural processing of faces is an early predictor of later ASD diagnosis. Furthermore, we identified two brain response-defined subgroups in ASD that showed distinct alterations in different aspects of face processing compared to siblings without ASD diagnosis, suggesting that individual differences between infants contribute to the diffuse pattern of alterations predictive of ASD in the first year of life. This study shows that moving from group-level comparisons to pattern recognition and stratification can help to understand and reduce heterogeneity in clinical cohorts, and improve our understanding of the mechanisms that lead to later neurodevelopmental outcomes.General Scientific SummaryThis study suggests that neural processing of faces is diffusely atypical in Autism Spectrum Disorder, and that it represents a strong candidate predictor of outcome at an individual level in the first year of life.
Efficacy and safety of turmeric extracts in knee osteoarthritis: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Wang Zhiqiang , Singh Ambrish , Antony Benny 
Published: May 2020

AbstractTurmeric extracts have been used as a remedy for treating arthritis in traditional medicine. Recent years have witnessed the rise of different extracts from turmeric and randomised clinical trials (RCTs) evaluating the efficacy and safety of these extracts for the treatment of knee osteoarthritis (OA). This planned systematic review and meta-analysis aims to assess the efficacy and safety of turmeric extracts for the treatment of knee OA. Biomedical databases such as PubMed, Scopus, and Embase will be searched for RCTs reporting safety and efficacy of turmeric extracts for the treatment of knee OA. Cochrane risk of bias tool will be used to assess the methodological quality of the included studies, and a meta-analysis will be performed to pool the effect estimates.
Associations with covid-19 hospitalisation amongst 406,793 adults: the UK Biobank prospective cohort study
Authors: Khawaja Anthony P , Warwick Alasdair N , Hysi Pirro G , Kastner Alan , Dick Andrew , Khaw Peng T , Tufail Adnan , Foster Paul J , Khaw Kay-Tee 
Published: May 2020

ABSTRACTOBJECTIVESTo identify the sociodemographic, lifestyle, comorbidity and antihypertensive medication associations with the development of hospitalisation with covid-19 in an English population.DESIGNProspective cohort studySETTINGThe population-based UK Biobank study was linked to English covid-19 test results.PARTICIPANTSIndividuals resident in England and alive in 2020.MAIN OUTCOME MEASURESCases (n=605) were defined by a positive covid-19 test result conducted between 16th March and 16th April 2020, during a restricted testing policy for hospitalised individuals with severe disease.RESULTSA total of 406,793 participants were included. Mean age on 1st January 2020 was 68 years (range 48 to 85 years). 55% were women. In multivariable models, major independent risk factors for hospitalisation with covid-19 were male sex (odds ratio 1.52; 95% confidence interval 1.28 to 1.81; P<0.001), South Asian ethnicity (2.02; 1.28 to 3.17; P=0.002) or black ethnicity (3.09; 2.18 to 4.38; P<0.001) compared to white ethnicity, greater residential deprivation (1.92 for most deprived quartile compared to least deprived quartile; 1.50 to 2.47; P<0.001), higher BMI (2.04 for BMI >35 compared to <25 Kg/m2; 1.50 to 2.77; P<0.001), former smoking (1.39 compared to never smoked; 1.16 to 1.66; P<0.001), and comorbidities hypertension (1.28; 1.06 to 1.53; P=0.009) and chronic obstructive pulmonary disease (1.81; 1.34 to 2.44; P<0.001). Increased risk was observed with increasing number of antihypertensive medications used rather than any individual class.CONCLUSIONUnderstanding why these factors confer increased risk of severe covid-19 in the population may help elucidate the underlying mechanisms as well as inform strategy and policy to prevent this disease and its consequences. We found no evidence of increased risk with specific classes of antihypertensive medication.
A study on the relationship between BCG vaccination and Covid-19 prevalence: Do other confounders warrant investigation?
Authors: Mariita Richard M. , Musila Jonathan M. 
Published: May 2020

AbstractThe Covid-19 pandemic, which originated from Wuhan, Hubei province, China, and quickly spread to the rest of the globe is caused by SARS-CoV-2, a single-stranded RNA virus. Preliminary data suggest a relationship between the BCG vaccine and the prevalence of Covid-19. The BCG vaccine is used in the prevention of tuberculosis, a disease that is most prevalent in developing countries. To determine the potential protective role of BCG vaccination, this study investigated the occurrence of Covid-19 and the relationship between the spread of Covid-19 in countries that offer BCG vaccination and those that do not. The study also performed a phylogenetic analysis of the strains involved in the Covid-19 outbreak from the representative countries. To achieve the objectives, the study utilized publicly available data on population size, vaccination coverage, and Covid-19 cases. Phylogenetic analysis was used to determine if some SARS-CoV-2 strains were more prevalent than others. The study revealed a significant negative trend between countries that offer the BCG vaccine to the general population and the reported cases of Covid-19. The study proposes future molecular and immunological analyses to determine the potential role of BCG vaccination in protection against Covid-19. This will determine if BCG has antiviral properties, with the possibility of recommending it for widespread use if supported by scientific data.
The first 6 weeks – setting up a UK urgent dental care centre during the COVID-19 pandemic
Authors: Carter Emily , Currie Charlotte C , Asuni Abisola , Goldsmith Rachel , Toon Grace , Horridge Catherine , Simpson Sarah , Donnell Christopher , Greenwood Mark , Walton Graham , Cole Ben , Durham Justin , Holliday Richard 
Published: May 2020

AbstractIntroductionThe COVID-19 pandemic has posed many challenges, including provision of urgent dental care. This paper presents a prospective service evaluation during establishment of urgent dental care in the North-East of England over a six-week period.AimTo monitor patient volumes, demographics and outcomes at the North-East urgent dental care service and confirm appropriate care pathways.Main Outcome MethodsData were collected on key characteristics of patients accessing urgent care from 23rd March to 3rd May 2020. Analysis was with descriptive statistics.ResultsThere were 1746 patient triages, (1595 telephone and 151 face-to-face) resulting in 1322 clinical consultations. The most common diagnoses were: symptomatic irreversible pulpitis or apical periodontitis. 65% of clinical consultations resulted in extractions, 0.5% an aerosol generating procedure. Patients travelled 25km on average to access care, however this reduced as more urgent care centres were established. The majority of patients were asymptomatic of COVID-19 and to our knowledge no staff acquired infection due to occupational exposure.ConclusionThe urgent dental care centre effectively managed urgent and emergency dental care, with appropriate patient pathways established over the 6-week period. Dental preparedness for future pandemic crisis could be improved and informed by this data.Three In Brief PointsA summary is given of how urgent dental care was established in the North East of England during the COVID-19 pandemic which may help with future preparedness for pandemics.Aerosol generating procedures were almost always avoided in the delivery of urgent dental careA telephone triage system was effectively used to determine who needed clinical care, and to separate symptomatic, asymptomatic and shielding patients, with very few failures in triage noted.
How robust are the results of one of the first positive trials exploring hydroxychloroquine for treatment of COVID-19?
Authors: Chow Ronald , Elsayed Sameer , Lock Michael 
Published: May 2020

AbstractAn outbreak of a novel human coronavirus infection emerged in Wuhan, China in December 2019. Two months later, the World Health Organization (WHO) announced SARS-CoV-2 as the name for the new virus and COVID-19 for the associated illness. On March 12, 2020, the WHO officially declared COVID-19 as a pandemic. The scientific community has raced to find effective therapeutic agents against the virus. Gautret et al 2020 is among one of the first purportedly positive trials of hydroxychloroquine for the treatment of COVID-19. However, it is imperative that a thorough analysis and understanding of trial data be undertaken prior to making claims about safety and efficacy. Our group assessed the statistical robustness of the trial using the Fragility Index (FI). The FI provides a numerical quantification of a clinical trial’s conclusions. The index is based on iterative statistical calculations to determine the minimum number of events within a trial that would theoretically need to change from positive to negative in order for the trial’s endpoint to convert from significant to non-significant; the higher the index, the more statistically robust the study results. For the Gautret et al trial, one endpoint had an FI of 1, two had indices of 2, and another had an index of 4. The primary endpoint of viral clearance on day 6 had an FI of 4. This indicates that if 4 events were to change from positive to negative, the conclusion of the trial would become mathematically non-significant. This index is comparable to many other published trials of established agents; the median FI across the reported literature appears to be 2. In conclusion, the trial results reported by Gautret et al are statistically robust, assuming that data quality is not compromised; however, the study was an open-label trial with non-homogenous groups, with analysis conducted per-protocol. Additionally, SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) testing was not conducted in a systematic way amongst the two groups. Further analyses of this trial and future trials of antiviral agents with potential activity against SARS-CoV-2 should be performed with complementary epidemiologic and statistical techniques to determine whether the trial’s results are clinically important and/or should be explored in depth. Given the statistically robust results reported by Gautret et al, despite the study’s inherent methodological and analytical flaws, hydroxychloroquine should be studied as a potential agent against COVID-19 in larger clinical trials.
Quantitative analysis of the iris surface smoothness by spectral domain optical coherence tomography in Fuchs uveitis
Authors: Zarei Mohammad , Pour Elias Khalili , Ebrahimiadib Nazanin , Riazi-Esfahani Hamid 
Published: May 2020

AbstractPurposeTo demonstrate the value of “smoothness index” as a novel tool for quantitative analysis of iris surface findings in unilateral Fuchs’ uveitis (FU).MethodsIn this observational study, both phakic eyes from patients with the diagnosis of unilateral FU were enrolled. All eyes underwent a complete ophthalmic examination and anterior segment optical coherence tomography(AS-OCT). The images were extracted and exported to the ImageJ software for calculating the “smoothness index (SI)”. The SI was defined as ratio of length of the straight line connecting the most peripheral and the most central points of anterior iris surface to actual length of this boundary.ResultsForty eyes from 20 patients with unilateral FU were enrolled. Mean age of patients was 40±10 years. Mean overall SI was 0.876± 0.030 in eyes with FU that was significantly more than fellow control eyes (0.841± 0.041). (p=0.005) The mean temporal and nasal SI were 0.878± 0.035 and 0.874± 0.033 in eyes with FU, compared to 0.843± 0.041 and 0.838± 0.047 in control fellow eyes, respectively. (p = 0.008 and p = 0.009, respectively)ConclusionIris “smoothness index” is a novel index to quantitatively document diffuse smoothness of iris anterior surface in eyes with FU. This index may facilitate diagnosis of subtle iris atrophic changes in these eyes, especially when heterochromia is absent.
Born to be young: prenatal thyroid hormones increase early-life telomere length
Authors: Stier Antoine , Hsu Bin-Yan , Marciau Coline , Doligez Blandine , Gustafsson Lars , Bize Pierre , Ruuskanen Suvi 
Published: May 2020

AbstractPrenatal environmental conditions can have lifelong consequences on health and aging. The underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we manipulated embryo exposure to maternal THs through egg injection and investigated the consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus confirming that these two molecular markers are hallmarks of aging in our wild bird model. The experimental elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal THs had no effect on mtDNA copy number but significantly increased telomere length both soon after birth and at the end of the growth period (equivalent to offsettingca.4 years of post-growth telomere shortening). These findings suggest that prenatal THs have a key role in setting the ‘biological’ age at birth, and thus might influence longevity.
Treatments administered to the first 9,152 reported cases of COVID19: a systematic review
Authors: Fajgenbaum David C. , Khor Johnson S. , Gorzewski Alek , Tamakloe Mark-Avery , Powers Victoria , Kakkis Joseph J. , Repasky Mileva , Taylor Anne , Beschloss Alexander , Hernandez-Miyares Laura , Go Beatrice , Nimgaonkar Vivek , McCarthy Madison S. , Kim Casey J. , Wing Anna , Mayer Michael A. , Pai Ruth-Anne Langan , Frankl Sarah , Fisher Megan , Germi James , Keyser Cornelia A. , Angelides Philip , Amurthur Ashwin , Jiang Joanna , Rasheed Rozena , Rodriguez-Lopez Eric , Napier Erin , Martins Bruna , Bambury Stephen , Gunderson Karen , Goodyear Nick , Mackay Duncan , Pierson Sheila K. 
Published: May 2020

AbstractThe emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID19 patients and assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between 12/1/2019–3/27/2020. Data were analyzed descriptively. Of the 2,706 articles identified, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalized and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically-meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There was insufficient data to compare across treatments. A large number of treatments have been administered to the first 9,152 reported cases of COVID19. These data serve as the basis for an open-source registry of all reported treatments given to COVID19 patients. Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.
What factors increase the risk of complications in SARS-CoV-2 positive patients? A cohort study in a nationwide Israeli health organization
Authors: Yanover Chen , Mizrahi Barak , Kalkstein Nir , Marcus Karni , Akiva Pinchas , Barer Yael , Shalev Varda , Chodick Gabriel 
Published: May 2020

AbstractReliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. To date, the most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we analyze the complete medical records of all SARS-CoV-2 infected individuals (N=4,353) in a large Israeli health organization (representing a population of 2.3 million people), of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals ≥ 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.
The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak
Authors: Emery Jon C , Russell Timothy W , Liu Yang , Hellewell Joel , Pearson Carl AB ,   CMMID 2019-nCoV working group, Knight Gwenan M , Eggo Rosalind M , Kucharski Adam J , Funk Sebastian , Flasche Stefan , Houben Rein M G J 
Published: May 2020

AbstractBackgroundSome key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship.MethodsWe used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals.FindingsOn the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15.InterpretationAsymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.FundingERC Starting Grant (#757699), Wellcome trust (208812/Z/17/Z), HDR UK (MR/S003975/1)