bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Clinical trial for Evaluation of BCG as potential therapy for COVID-19
Authors: Padmanabhan Usha , Mukherjee Sanjay , Borse Rohidas , Joshi Sameer , Deshmukh Rajesh 
Published: November 2020

AbstractBacillus Calmette−Guérin (BCG) is widely used in national vaccination programs worldwide. It is accepted that BCG alleviates both pathogen and allergy induced respiratory diseases that could also include Covid-19. To investigate this possibility, we randomly assigned 60 Covid-19 patients, after admission to the hospital with pneumonia and requirement for oxygen therapy in a 1:1 ratio to receive either a single adult dose of intradermal BCG or normal saline with concomitant standard of care (SoC) medications. Primary endpoints were favorable prognosis of Covid-19 as deduced from resolution of pneumonia, viremia and secondary outcome were enumeration of ICU admissions, duration thereof and mortalities.ResultsBoth primary and secondary endpoints were significantly improved in the BCG+SoC group. This could be seen from reduction in oxygen requirement due to Covid-19 associated pneumonia decreasing from day 3-4, improved radiological resolution from day 7-15. There were a total of 6 (10%) adverse events in the study of which 2 deaths and 4 ICU admissions were in SoC group (1 ICU admission culminated in death of the subject) and in contrast only 1 ICU admission in the BCG+SoC group. While there was an increase in Covid-19 specific IgG levels in the BCG+SoC group, there was no evidence of BCG induced cytokine storm in this group. Four patients showed localized inflammatory response at the injection site in the BCG+SoC group.ConclusionsBCG+SoC administration resulted in a significantly higher percentage of patients with favorable outcomes than did SoC. A third of the patients were naïve for childhood BCG vaccination. This mimicked elderly patients in countries with no universal vaccination policy for BCG. No BCG related adversity was seen in this group. The study shows that BCG is a safe, cost-effective treatment that can be introduced as a standard of care in patients with moderate Covid-19 that can reduce requirement of oxygen supplemented beds and disease burden in low resource countries, with additional long-term benefits of reducing risk for tuberculosis.
A Time-dependent mathematical model for COVID-19 transmission dynamics and analysis of critical and hospitalized cases with bed requirements
Authors: Singh Avaneesh , Bajpai Manish Kumar , Gupta Shyam Lal 
Published: November 2020

AbstractA time-dependent SEAIHCRD model is the extension of the SEIR model, which includes some new compartment that is asymptomatic infectious people, hospitalized people, critical people, and dead compartments. In this article, we analyzed six countries, namely the United States, Brazil, India, South Africa, Russia, and Mexico. A time-dependent SEAIHCRD model calculates the magnitude of peaks for exposed people, asymptomatic infectious people, symptomatic infectious people, hospitalized people, the number of people admitted to ICUs, and the number of COVID-19 deaths over time. It also computes the spread scenario and endpoints of disease. The proposed model also involves asymptomatic infectious individuals. To estimate the various parameters, we first collect the data and fit that using the Lavenberg-Marquardt model for death cases. Then we calculate infection rate, recovery rate, case fatality rate, and the basic reproduction number over time. We calculate two types of case fatality rates: one is the daily case fatality rate, and the other is the total case fatality rate. The proposed model includes the social distance parameter, various age classes, hospital beds for severe cases, and ICU beds or ventilators for critical cases. This model will be useful to determine various essential parameters such as daily hospitalization rate, daily death rates, including the requirement of normal and ICU beds during peak days of infection.
Diagnostic concordance between physiotherapist and emergency physicians for patients with a musculoskeletal disorder in the emergency department
Authors: Gagnon Rose , Perreault Kadija , Brun Gabrielle , Matifat Eveline , Desmeules François , Berthelot Simon , Hébert Luc J. 
Published: November 2020

ABSTRACTQuestionWhat is the level of diagnostic concordance between physicians and physiotherapists for patients consulting in an emergency department (ED) with musculoskeletal disorders (MSKDs)?DesignSecondary analysis of data obtained through a pragmatic randomized controlled trial, physiotherapist (PT) and emergency physicians (EPs) unblinded, per-protocol analysis.Participants78 participants aged 18 to 80 years presenting with a minor MSKD were recruited and data from the 40 participants randomized in the intervention group were used (mean age 36.6 yrs (SD: 17.3, IQR: 22.0; 46.8); women: 55%).Outcome measuresDiagnostic concordance was established using the International Classification of Diseases 11 (ICD-11) and examined between EP and PT using raw agreement and Gwet’s first-order agreement coefficient (AC1).ResultsForty participants were recruited and 36 were assessed by the PT and EP (36.8 ± 18.2 years old; 55.6% women). Overall raw agreement was 86.1% and an almost perfect diagnostic concordance was observed between PT and EP (Gwet’s AC1: 0.84, 95% CI: 0.69 – 0.98). The most common reason for disagreement was suspected bone fracture or contusion in comparison with ligament or meniscus disorder.ConclusionResults from this study indicate that overall diagnostic concordance between PT and EP in the ED for patients consulting with MSKDs is almost perfect. These results tend to support the safety of such models of care. However, more studies are needed to confirm these results as the EP wasn’t always independent and the classification used was imprecise.Registration#NCT04009369
A catalog of associations between rare coding variants and COVID-19 outcomes
Authors: Kosmicki J. A. , Horowitz J. E. , Banerjee N. , Lanche R. , Marcketta A. , Maxwell E. , Bai X. , Sun D. , Backman J. D. , Sharma D. , Kang H. M. , O’Dushlaine C. , Yadav A. , Mansfield A. J. , Li A. H. , Watanabe K. , Gurski L. , McCarthy S. E. , Locke A. E. , Khalid S. , O’Keeffe S. , Mbatchou J. , Chazara O. , Huang Y. , Kvikstad E. , O’Neill A. , Nioi P. , Parker M. M. , Petrovski S. , Runz H. , Szustakowski J. D. , Wang Q. , Wong E. , Cordova-Palomera A. , Smith E. N. , Szalma S. , Zheng X. , Esmaeeli S. , Davis J. W. , Lai Y-P. , Chen X. , Justice A. E. , Leader J. B. , Mirshahi T. , Carey D. J. , Verma A. , Sirugo G. , Ritchie M. D. , Rader D. J. , Povysil G. , Goldstein D. B. , Kiryluk K. , Pairo-Castineira E. , Rawlik K. , Pasko D. , Walker S. , Meynert A. , Kousathanas A. , Moutsianas L. , Tenesa A. , Caulfield M. , Scott R. , Wilson J. F. , Baillie J. K. , Butler-Laporte G. , Nakanishi T. , Lathrop M. , Richards J.B. ,   Regeneron Genetics Center,   UKB Exome Sequencing Consortium, Jones M. , Balasubramanian S. , Salerno W. , Shuldiner A. R. , Marchini J. , Overton J. D. , Habegger L. , Cantor M. N. , Reid J. G. , Baras A. , Abecasis G. R. , Ferreira M. A. 
Published: November 2020

ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable athttps://rgc-covid19.regeneron.com.
Occupational risk of COVID-19 in the 1stvs 2ndwave of infection
Authors: Magnusson Karin , Nygård Karin , Methi Fredrik , Vold Line , Telle Kjetil 
Published: November 2020

AimTo study whether employees in occupations that typically imply close contact with other people are tested more and at higher risk of confirmed SARS-CoV-2 infection (COVID-19) and related hospitalization, in the 1stand 2ndwave of infection in Norway.MethodsIn all 3 559 694 residents of Norway on January 1st2020 aged 20-70 (with mean [SD] age 44.1 [14.3] years and 51% men), we studied COVID-19 testing patterns sorted by occupation (using Standard Classification of Occupations [ISCO-08]). We also studied whether selected occupations had a higher risk of 1) confirmed COVID-19 and 2) hospitalization with COVID-19, compared to everyone else aged 20-70 years using logistic regression adjusted for age, sex, testing behavior, and own and maternal country of birth.ResultsOccupations with high frequency of testing (e.g. health personnel and teachers) had a low frequency of positive tests. Nurses, physicians, dentists, physiotherapists, bus/tram and taxi drivers had 1.1-4 times the odds of COVID-19 during the 1stwave, whereas bartenders, waiters, transport conductors and travel stewards had 1.1-3 times the odds of COVID-19 during the 2ndwave (when compared to everyone else). Teachers had moderately increased odds of COVID-19. Occupation may be of limited relevance for hospitalization with the disease.ConclusionStudying the entire Norwegian population using international standardized codes of occupations, our findings may be of relevance to national and regional authorities in handling the pandemic. Also, our findings provide a knowledge foundation for the more targeted future studies of lockdown, testing strategies and disease control measures.
Using RT-PCR Testing to Assess the Effectiveness of Outbreak Control Efforts in São Paulo State, the Pandemic’s Epicenter in Brazil, according to Socioeconomic Vulnerabilities
Authors: Sousa Tatiane C M , Moreira Natália P , Krieger Jose E. , Rosa Isabel S C , Zamudio Marcela M. , Veras Maria Amélia S M , Kemp Brigina , Barberia Lorena G. 
Published: November 2020

AbstractBackgroundThe testing of infected persons with SARS-CoV-2 is one of the cornerstones of an effective strategy deployed for pandemic control. The public health diagnostic effort is particularly important in regions with a critical transmission scenario and in vulnerable populations in these districts, such as São Paulo state, the Brazilian epicenter of the COVID-19 pandemic.MethodsWe developed an RT-PCR testing intensity effort index (RT-PCR TIEI) composed of seven indicators to assess the survelliance efforts in the São Paulo State. We used dynamic time-series cross-sectional models to analyze the association between the RT-PCR TIEI, the population living under high socioeconomic vulnerability levels, dependent on public health service (SUS), per capita income, and population density.ResultsOn average, the RT-PCR TIEI score was 21.07. In the long-run, the RT-PCR TIEI is negatively associated with socioeconomic vulnerability (p-value=0.000, 95% CI −0.887, - 0.811), with a higher proportion of the population dependent on SUS (p-value= 0.000, 95% CI −0.871, −0.805), per capita income (p-value= 0.000, 95% CI −0.849,-0.792) and with population density (p-value=0.000, 95% CI −0.853; −0.801).ConclusionTesting efforts declined as the pandemic advanced, and the the lowest RT-PCR TIEI values were found in the most socioeconomic vulnerable RHDs. Local public laboratory presence was a predictor of a higher score. Thus, the low testing RT-PCR efforts and local laboratory inequalities affected surveillance capability, especially for socioeconomic vulnerable populations.
Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus
Authors: Gupta Sarthak , Nakabo Shuichiro , Chu Jun , Hasni Sarfaraz , Kaplan Mariana J. 
Published: November 2020

AbstractObjectivesAnti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients.MethodsPatients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry.ResultsTen SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation.None of the other SLE samples blocked IFNα signaling.ConclusionsWe noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.Key MessagesWhat is already known about this subject?-Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE) and have recently been associated with severe COVID-19 in the general population.What does this study add?-SLE subjects with COVID-19 had an increased prevalence of pre-existing anti-IFNα autoantibodies compared to the reported prevalence in lupus patients and the general population with severe COVID-19.-Plasma from 50% of subjects with these autoantibodies were able to block in vitro activity of IFNα.-SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19 manifestations.How might this impact on clinical practice or future developments?-Anti-IFNα autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients.
Border Restriction as a Public Health Measure to Limit Outbreak of Coronavirus Disease 2019 (COVID-19)
Authors: Wang Chun Kwok , Chun Ka Wong , Ting Fung Ma , Ka Wai Ho , Wai Tong Louis Fan , King Pui Florence Chan , Shung Kay Samuel Chan , Chi Chun Terence Tam , Pak Leung Ho 
Published: November 2020

AbstractBackgroundCoronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.MethodA novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration was applied to investigate the effect of border restriction between Hong Kong and mainland China on the epidemiological characteristics of COVID-19 in Hong Kong. Isolation facilities occupancy was also studied.ResultsAt R0 of 2·2, the cumulative COVID-19 cases in Hong Kong can be reduced by 13·99% (from 29,163 to 25,084) with complete border closure. At an in-patient mortality of 1·4%, the number of deaths can be reduced from 408 to 351 (57 lives saved). However, border closure alone was insufficient to prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1·6 was necessary.ConclusionAs a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality.Article summaryStrengths and limitations of this studyA novel metapopulation SEIR model with inspected migration was developed to investigate the epidemiological characteristics of COVID-19 in Hong Kong, Guangdong and the rest of China (excluding Hubei) in the presence or absence of border restriction.The presented model is also suitable for further analysis of other emerging infectious diseases.Border restriction is an effective public health measure in reducing cumulative cases and mortality for COVID-19.Interaction was assumed to be well-mixed within patch. The spatial effect in disease transmission within each patch is ignored, which can have a non-trivial effect on the dynamic of infectious disease.The proposed model is deterministic in nature which ignores the randomness in migration and in the interactions among people; a stochastic model would be more realistic especially early in the disease.
A minimal model for household-based testing and tracing in epidemics
Authors: Huber Greg , Kamb Mason , Kawagoe Kyle , Li Lucy M. , McGeever Aaron , Miller Jonathan , Veytsman Boris , Zigmond Dan 
Published: November 2020

AbstractIn a previous work [1], we discussed virus transmission dynamics modified by a uniform clustering of contacts in the population: close contacts within households and more distant contacts between households. In this paper, we discuss testing and tracing in such a stratified population. We propose a minimal tracing strategy consisting of random testing of the entire population plus full testing of the households of those persons found positive. We provide estimates of testing frequency for this strategy to work.
Avoiding versus contracting COVID-19: On the effectiveness of social distancing at the level of the individual
Authors: Fazio Russell H. , Ruisch Benjamin C. , Moore Courtney A. , Granados Samayoa Javier A. , Boggs Shelby T. , Ladanyi Jesse T. 
Published: November 2020

AbstractPast research has established the value of social distancing as a means of deterring the spread of COVID-19 largely by examining aggregate level data. Locales in which efforts were undertaken to encourage distancing experienced reductions in their rate of transmission. However, these aggregate results tell us little about the effectiveness of social distancing at the level of the individual, which is the question addressed by the current research. Four months after participating in a study assessing their social distancing behavior, 2,120 participants indicated whether they had contracted COVID-19. Importantly, the assessment of social distancing involved not only a self-report measure of how strictly participants had followed social distancing recommendations, but also a series of virtual behavior measures of social distancing. These simulations presented participants with graphical depictions mirroring specific real-world scenarios, asking them to position themselves in relation to others in the scene. Individuals’ social distancing behavior, particularly as assessed by the virtual behavior measure, predicted whether they contracted COVID-19 during the intervening four months. This was true when considering only participants who reported having tested positively for the virus and when considering additional participants who, although untested, believed that they had contracted the virus. The findings offer a unique form of additional evidence as to why individuals should practice social distancing. What the individual does matters, not only for the health of the collective, but also for the specific individual.
AI-Powered Effective Lens Position Prediction Improves the Accuracy of Existing Lens Formulas
Authors: Li Tingyang , Stein Joshua D. , Nallasamy Nambi 
Published: November 2020

ABSTRACTAimsTo assess whether incorporating a machine learning (ML) method for accurate prediction of postoperative anterior chamber depth (ACD) improves the refraction prediction performance of existing intraocular lens (IOL) calculation formulas.MethodsA dataset of 4806 cataract patients were gathered at the Kellogg Eye Center, University of Michigan, and split into a training set (80% of patients, 5761 eyes) and a testing set (20% of patients, 961 eyes). A previously developed ML-based method was used to predict the postoperative ACD based on preoperative biometry. This ML-based postoperative ACD was integrated into new effective lens position (ELP) predictions using regression models to rescale the ML output for each of four existing formulas (Haigis, Hoffer Q, Holladay, and SRK/T). The performance of the formulas with ML-modified ELP was compared using a testing dataset. Performance was measured by the mean absolute error (MAE) in refraction prediction.ResultsWhen the ELP was replaced with a linear combination of the original ELP and the ML-predicted ELP, the MAEs ± SD (in Diopters) in the testing set were: 0.356 ± 0.329 for Haigis, 0.352 ± 0.319 for Hoffer Q, 0.371 ± 0.336 for Holladay, and 0.361 ± 0.331 for SRK/T which were significantly lower than those of the original formulas: 0.373 ± 0.328 for Haigis, 0.408 ± 0.337 for Hoffer Q, 0.384 ± 0.341 for Holladay, and 0.394 ± 0.351 for SRK/T.ConclusionUsing a more accurately predicted postoperative ACD significantly improves the prediction accuracy of four existing IOL power formulas.
Is degree of sociality associated with reproductive senescence? A comparative analysis across birds and mammals
Authors: Vágási Csongor I. , Vincze Orsolya , Lemaître Jean-François , Pap Péter L. , Ronget Victor , Gaillard Jean-Michel 
Published: November 2020

Our understanding on how widespread reproductive senescence is in the w ild and how the onset and rate of reproductive senescence vary among species in relation to life histories and lifestyles is currently limited. More specifically, whether the species-specific degree of sociality is linked to the occurrence, onset and rate of reproductive senescence remains unknown. Here, we investigate these questions using phylogenetic comparative analyses across 36 bird and 101 mammal species encompassing a wide array of life histories, lifestyles and social traits. We found that female reproductive senescence (1) is widespread and occurs with similar frequency (about two thirds) in birds and mammals; (2) occurs later in life and is slower in birds than in similar-sized mammals; (3) occurs later in life and is lower with an increasingly slower pace of life in both vertebrate classes; and (4) is only weakly associated, if any, with the degree of sociality in both classes after accounting for the effect of body size and pace of life. However, when removing the effect of species differences in pace of life, a higher degree of sociality was associated with later and weaker reproductive senescence in females, which suggests that degree of sociality is either indirectly related to reproductive senescence via the pace of life or simply a direct outcome of the pace of life.Subject Areasecology, evolution