bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective comparison of Bayesian and frequentist adaptive clinical trials : The SHADOW - SHINE project
Authors: Broglio Kristine , Meurer William J. , Durkalski Valerie , Pauls Qi , Connor Jason , Berry Donald , Lewis Roger J. , Johnston Karen C. , Barsan William G. 
Published: June 2021

AbstractImportanceBayesian adaptive trial design has the potential to create more efficient clinical trials. However, one of the barriers to the uptake of Bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared to a frequentist design.ObjectiveCompare the performance of a Bayesian and a frequentist adaptive clinical trial design.DesignProspective observational study comparing two trial designs using individual patient level data from a completed stroke trial, including the timing and order of enrollments and outcome ascertainment. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses when 90-days post-randomization was met for 500, 700, 900, and 1,100 patients. The Bayesian alternative utilized predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients, and subsequent interims after every 100 randomizations.SettingMulti-center, acute stroke study conducted within a National Institutes of Health neurological emergencies clinical trials network.ParticipantsPatient level data from 1,151 patients randomized in a clinical trial comparing intensive insulin therapy to standard in acute stroke patients with hyperglycemia.Main Outcome(s) and Measure(s)Sample size at end of study. This was defined as the sample size at which each of the studies stopped accrual of patients.ResultsAs conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the Bayesian alternative crossed the futility boundary about 3 months earlier after 800 participants were randomized.Conclusions and RelevanceBoth trial designs stopped for futility prior to reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trial’s primary question earlier. The common feature across the two designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how this was implemented between the two trials resulted in the differences in early stopping.Trial RegistrationThe SHINE trial was registered and results are reported on clinicaltrials.gov under identifier: NCT01369069
Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals
Authors: Melbourne Carl A. , Erzurumluoglu A. Mesut , Shrine Nick , Chen Jing , Tobin Martin D. , Hansell Anna , Wain Louise V. 
Published: June 2021

AbstractImpaired lung function is predictive of mortality and is a key component in the diagnosis of chronic obstructive pulmonary disease. Lung function has a strong genetic component but is also affected by environmental factors such as increased exposure to air pollution. How genetic factors and air pollution interact to affect lung function is however less understood.We conducted a genome-wide gene-air pollution interaction analysis of spirometry measures with three measures of air pollution at home address: particulate matter (PM2.5& PM10) and nitrogen dioxide (NO2), in approximately 300,000 unrelated European individuals from UK Biobank. We explored air pollution interactions with previously identified lung function signals and determined their combined interaction effect using a polygenic risk score (PRS).We identified seven genome-wide interaction signals (P< 5 × 10−8), and a further ten suggestive interaction signals (P< 5 × 10−7). We found statistical evidence of interaction with PM2.5for previous lung function signal, rs10841302, nearAEBP2, suggesting increased susceptibility of FEV1/FVC to PM2.5, as copies of the G allele increased (interaction beta: −0.073 percentage points, 95%CI: −0.105, −0.041). There was no observed interaction between air pollutants and the weighted genetic risk score.We carried out the largest genome-wide gene-air pollution interaction study of lung function and identified effects of clinically relevant size and significance. We observed up to 440ml lower lung function for certain genotypes associated with mean levels of outdoor air pollution at baseline, which is approximately equivalent to nine years of normal loss of lung function.
Comparison of antigen- and RT-PCR-based testing strategies for detection of Sars-Cov-2 in two high-exposure settings
Authors: Love Jay , Wimmer Megan T. , Toth Damon J.A. , Chandran Arthi , Makhija Dilip , Cooper Charles K. , Samore Matthew H. , Keegan Lindsay T. 
Published: June 2021

AbstractSurveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when administered to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.
SARS-CoV-2 Seroprevalence Among Firefighters in Los Angeles, California
Authors: Mulligan Karen , Berg Anders H. , Eckstein Marc , Hori Acacia , Rodriguez Anna , Toubat Omar , Sood Neeraj 
Published: June 2021

ABSTRACTObjectiveWe estimate the seroprevalence of SARS-CoV-2 antibodies among firefighters in the Los Angeles, California fire department in October 2020 and compare demographic and contextual factors for seropositivity.MethodsWe conducted a serologic survey of firefighters in Los Angeles, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for immunoglobulin G, immunoglobulin M, or both. We compared demographic and contextual factors for seropositivity.ResultsOf 713 participants, 8.9% tested positive for SARS-CoV-2 antibodies. Seropositivity was not associated with gender, age, or race/ethnicity. Furthermore, firefighters who worked in zip codes with lower income or higher share of minority population did not have higher rates of SARS-CoV-2 infection. Seropositivity was highest among firefighters who reported working in the vicinity of Los Angeles International Airport, which had a known outbreak in July 2020.ConclusionsSeroprevalence among firefighters was no higher than seroprevalence in the general population, suggesting that workplace safety protocols, such as access to PPE and testing, can mitigate increased risk of infection at work. Workplace safety protocols for firefighters also eliminated differences in disease burden by geography and race/ethnicity observed in the general population.
Lead exposure and serum metabolite profiles in pregnant women in Mexico City
Authors: Niedzwiecki Megan M. , Eggers Shoshannah , Joshi Anu , Dolios Georgia , Cantoral Alejandra , Lamadrid-Figueroa Héctor , Amarasiriwardena Chitra , Téllez-Rojo Martha M. , Wright Robert O. , Petrick Lauren 
Published: June 2021

AbstractBackgroundLead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb.MethodsWe used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted.ResultsThe median (interquartile range) blood Pb concentration was 2.9 (2.6) μg/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) μg/g and 3.6 (9.5) μg/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures.ConclusionThis study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.
Comparison of bacterial communities from the surface and adjacent bottom layers water of Billings reservoir
Authors: Marcondes Marta Angela , Nascimento Andrezza , Pessôa Rodrigo , Victor Jefferson Russo , da Silva Duarte Alberto José , Sanabani Sabri Saeed 
Published: June 2021

ABSTRACTHere, we describe the microbial diversity and physicochemical properties in freshwater samples from the surface and bottom layer of Billings reservoir in São Paulo state, Brazil. Twenty-two matched samples were characterized using the 16S rRNA gene Illumina MiSeq platform. Taxonomical composition revealed an abundance ofCyanobacteriaphyla, followed byProteobacteria, with 1903 and 2689 known bacterial genera in the surface and deep-water layers, respectively. Shannon diversity index ranging from 2.3 - 5.39 and 4.04 - 6.86 in the surface and bottom layer, respectively. Among the 120 pathogenic genera identified,Flavobacteriumwas the most predominant genus. Temperature and phosphorus concentration were the most influential factors in shaping the microbial communities of both layers. Predictive functional analysis suggests that the reservoir is enriched in motility genes involved in the flagellar assembly. The overall results present new information on the significantly altered diversity composition of the bacterial community detected in Billings freshwater reservoir.IMPORTANCEIn this study, we investigated the bacterial distribution, community composition, potential metabolic activity, potentially pathogenic bacteria, and toxin genes ofCyanobacteriain the bottom layers and surface along Billings reservoir in the southeast of Brazi. Our results provide essential information about the pattern of bacterioplankton communities’ variation inhabiting the Billings reservoir and the combination of environmental that shaped their structure. These results may help pave the way for future studies devoted to control and improve the water quality in the Billings reservoir, which is facing rapid urban development and urbanization.
Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD
Authors: Mandel-Brehm Caleigh , Benson Leslie A. , Tran Baouyen , Kung Andrew F. , Mann Sabrina A. , Vazquez Sara E. , Retallack Hanna , Sample Hannah A. , Zorn Kelsey C. , Khan Lillian M. , Kerr Lauren M. , McAlpine Patrick L. , Zhang Lichao , McCarthy Frank , Elias Joshua E. , Katwa Umakanth , Astley Christina M. , Tomko Stuart , Dalmau Josep , Seeley William W. , Pleasure Samuel J. , Wilson Michael R. , Gorman Mark P. , DeRisi Joseph L. 
Published: June 2021

AbstractROHHAD (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.
Introduction and transmission of SARS-CoV-2 B.1.1.7 in Denmark
Authors: Michaelsen Thomas Y. , Bennedbæk Marc , Christiansen Lasse E. , Jørgensen Mia S. F. , Møller Camilla H. , Sørensen Emil A. , Knutsson Simon , Brandt Jakob , Jensen Thomas B. N. , Chiche-Lapierre Clarisse , Collados Emilio F. , Sørensen Trine , Petersen Celine , Le-Quy Vang , Sereika Mantas , Hansen Frederik T. , Rasmussen Morten , Fonager Jannik , Karst Søren M. , Marvig Rasmus L. , Stegger Marc , Sieber Raphael N. , Skov Robert , Legarth Rebecca , Krause Tyra G. , Fomsgaard Anders ,   The Danish Covid-19 Genome Consortium (DCGC), Albertsen Mads 
Published: June 2021

AbstractIn early 2021, the SARS-CoV-2 lineage B.1.1.7 became dominant across large parts of the world. In Denmark, comprehensive and real-time test, contact-tracing, and sequencing efforts were applied to sustain epidemic control. Here, we use these data to investigate the transmissibility, introduction, and onward transmission of B.1.1.7 in Denmark. In a period with stable restrictions, we estimated an increased B.1.1.7 transmissibility of 58% (95% CI: [56%,60%]) relative to other lineages. Epidemiological and phylogenetic analyses revealed that 37% of B.1.1.7 cases were related to the initial introduction in November 2020. Continuous introductions contributed substantially to case numbers, highlighting the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants.
The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials
Authors: Wafa Ifan Ali , Pratama Nando Reza , Budi David Setyo , Sutanto Henry , Rosyid Alfian Nur , Wungu Citrawati Dyah Kencono 
Published: June 2021

AbstractObjectivesThe use of monoclonal antibody for COVID-19 showed conflicting results in prior studies and its efficacy remains unclear. We aimed to comprehensively determine the efficacy and safety profile of monoclonal antibodies in COVID-19 patients.MethodsSixteen RCTs were analyzed using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs.ResultsThe pooled effect of monoclonal antibodies demonstrated mortality risk reduction (RR=0.89 (95%CI 0.82-0.96), I2=13%, fixed-effect). Individually, tocilizumab reduced mortality risk in severe to critical disease (RR=0.90 (95%CI 0.83-0.97), I2=12%, fixed-effect)) and lowered mechanical ventilation requirements (RR=0.76 (95%CI 0.62-0.94), I2=42%, random-effects). Moreover, it facilitated hospital discharge (RR=1.07 (95%CI 1.00-1.14), I2=60%, random-effects). Meanwhile, bamlanivimab-etesevimab and REGN-COV2 decrease viral load ((SMD=-0.33 (95%CI -0.59 to -0.08); (SMD=-3.39 (95%CI -3.82 to -2.97)). Interestingly, monoclonal antibodies did not improve hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99–1.12), I2=71%, random-effects) and they displayed similar safety profile with placebo/standard therapy (RR=1.04 (95%CI 0.76-1.43), I2=54%, random-effects).ConclusionTocilizumab improved hospital discharge and reduced mortality as well as the need for mechanical ventilation, while bamlanivimab-etesevimab and REGN-COV2 reduced viral load in mild to moderate outpatients. In general, monoclonal antibodies are safe and should be considered in severe to critical COVID-19 patients.RegistrationPROSPERO (CRD42021235112)
Estimating Time-Dependent Disease Transmission Intensity using Reported Data: An Application to Ebola and Selected Public Health Problems
Authors: Mubayi Anuj , Pandey Abhishek , Brasic Christine , Mubayi Anamika , Ghosh Parijat , Ghosh Aditi 
Published: June 2021

AbstractObtaining reasonable estimates for transmission rates from observed data is a challenge when using mathematical models to study the dynamics of “infectious” diseases, like Ebola. Most models assume the transmission rate of a contagion does not vary over time. However, these rates do vary during an epidemic due to environmental conditions, social behaviors, and public-health interventions deployed to control the disease. Therefore, obtaining time-dependent rates can aid in understanding the progression of disease through a population. We derive an analytical expression using a standard SIR-type mathematical model to compute time-dependent transmission rate estimates for an epidemic in terms of either incidence or prevalence type available data. We illustrate applicability of our method by applying data on various public health problems, including infectious diseases (Ebola, SARS, and Leishmaniasis) and social issues (obesity and alcohol drinking) to compute transmission rates over time. We show that transmission rate estimates can have a large variation over time, depending on the type of available data and other epidemiological parameters. Time-dependent estimation of transmission rates captures the dynamics of the problem and can be utilized to understand disease progression through population accurately. Alternatively, constant estimations may provide unacceptable results that could have major public health consequences.
Low frequency interictal EEG biomarker for localizing seizures
Authors: Lundstrom Brian Nils , Brinkmann Benjamin , Worrell Gregory 
Published: June 2021

AbstractObjectiveWe want to identify seizure onset zone (SOZ) from interictal EEG biomarkers. We hypothesize that a combination of interictal EEG biomarkers, including a novel low frequency marker, can predict mesial temporal involvement and can assist in prognosis related to surgical resections.MethodsInterictal direct current wide bandwidth invasive EEG recordings from 83 patients implanted with 5,111 electrodes were retrospectively studied. Logistic regression was used to classify electrodes and patient outcomes. A feed-forward neural network was implemented to understand putative mechanisms.ResultsInterictal infraslow frequency EEG activity was decreased for SOZ electrodes while faster frequencies such as delta (2-4 Hz) and beta-gamma (20-50 Hz) activity were increased. These spectral changes comprised a novel interictal EEG biomarker that was significantly increased for mesial temporal SOZ electrodes compared to non-SOZ electrodes. Interictal EEG biomarkers correctly classified mesial temporal SOZ electrodes with a specificity of 87% and positive predictive value of 80%. These interictal EEG biomarkers also correctly classified patient outcomes after surgical resection with a specificity of 91% and positive predictive value of 87%.InterpretationInterictal infraslow EEG activity is decreased near the SOZ while higher frequency power is increased, suggesting distinct underlying physiologic mechanisms. Decreased interictal infraslow activity may reflect the loss of neural inhibition. Narrowband interictal EEG power bands provide information about the SOZ and can help predict mesial temporal involvement in seizure onset. Together with interictal epileptiform discharges and high frequency oscillations, these interictal biomarkers may provide prognostic information prior to surgical resection.
What is the main driver of unsustainable natural resource use in the Comoro Islands?
Authors: Ibouroi Mohamed Thani , Dhurham Said Ali Ousseni , Besnard Aurélien , Lescureux Nicolas 
Published: June 2021

ABSTRACTThe Comoros archipelago is a biodiversity hotspot by virtue of its high level of endemism. However, it suffers one of the highest rates of forest loss worldwide, mainly due to strong anthropogenic pressures. As Comorian populations depend on forest resources for subsistence, establishing relevant conservation strategies for their sustainable management requires the consideration of multiple stakeholders’ perspectives toward biodiversity and habitat conservation. To better understand the relationships between humans and nature; how comorian people use natural resource and the relevance of a protected area for long-term biodiversity conservation, we used Q-methodology to assess local people‘s perceptions regarding biodiversity and conservation actions. Three discourses are identified during analysis: “Pro-environment discourse”, “Keeping things as usual” and “Social and environmental concerns”. According to the results, employed respondents, were favorable to long-term forest and biodiversity conservation. In contrast, unemployed respondents were in favor of more immediate benefits while unemployed but educated respondents were in favor to both long-term forest conservation and immediate benefits from forests. This suggests that the lack of livelihoods for rural people is the main factor leading them to overharvest natural resources. These results suggest that biodiversity conservation of the Comoros archipelagos may benefit for plan aiming at (1) developing tourism and maintaining sustainable production of crops and livestock that could allow enhancing the livelihoods and well-being of all social groups, (2) developing projects such as local markets that could allow villagers to sell their agricultural production, (3) setting up awareness campaign for tree-planting and reforestation. Reforestation could allow re-establishing natural plants and make large trees available for long-term purposes.