bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Canadian ALS Neuroimaging Consortium (CALSNIC) - a multicentre platform for standardized imaging and clinical studies in ALS
Authors: Kalra Sanjay , Khan Muhammad , Barlow Laura , Beaulieu Christian , Benatar Michael , Briemberg Hannah , Chenji Sneha , Clua Miriam Garrido , Das Sumit , Dionne Annie , Dupré Nicolas , Emery Derek , Eurich Dean , Frayne Richard , Genge Angela , Gibson Summer , Graham Simon , Hanstock Christopher , Ishaque Abdullah , Joseph Jeffrey T. , Keith Julia , Korngut Lawrence , Krebs Dennell , McCreary Cheryl R. , Pattany Pradip , Seres Peter , Shoesmith Christen , Szekeres Trevor , Tam Fred , Welsh Robert , Wilman Alan , Yang Yee Hong , Yunusova Yana , Zinman Lorne ,   for the Canadian ALS Neuroimaging Consortium
Published: July 2020

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a disabling and rapidly progressive neurodegenerative disorder. Increasing age is an important risk factor for developing ALS, thus the societal impact of this devastating disease will become more profound as the population ages. A significant hurdle to finding effective treatment has been an inability to accurately quantify cerebral degeneration associated with ALS in humans. Advanced magnetic resonance imaging (MRI) techniques hold promise in providing a set of biomarkers to assist in aiding diagnosis and in efficiently evaluating new drugs to treat ALS.MethodsThe Canadian ALS Neuroimaging Consortium (CALSNIC) was founded to develop and evaluate advanced MRI-based biomarkers that delineate biological heterogeneity, track disease progression, and predict survival in a large and heterogeneous sample of ALS patients.FindingsCALSNIC has launched two studies to date (CALSINC-1, CALSNIC-2), acquiring multimodal neuroimaging, neurological, neuropsychological data, and neuropathological data from ALS patients and healthy controls in a prospective and longitudinal fashion from multiple centres in Canada and, more recently, the United States. Clinical and MRI protocols are harmonized across research centres and different MR vendors.InterpretationCALSNIC provides a multicentre platform for studying ALS biology and developing MRI-based biomarkers.FundingCanadian Institutes of Health Research, ALS Society of Canada, Brain Canada Foundation, Shelly Mrkonjic Research Fund
Serological Tests for SARS-CoV-2 Coronavirus by Commercially Available Point-of-Care and Laboratory Diagnostics in Pre-COVID-19 Samples in Japan
Authors: Sassa Mariko Harada , Lyu Zhaoqing , Fujitani Tomoko , Harada Kouji H. 
Published: July 2020

AbstractSerological tests for SARS-CoV-2 coronavirus in pre-COVID-19 samples in Japan showed 1.5%–1.75% positives, and previous surveys might overestimate COVID-19 seroprevalence in several population of Japan. These false negatives could be excluded by combination of different diagnostics to 0.25%.
Sample Size Calculation for Phylogenetic Case Linkage
Authors: Wohl Shirlee , Giles John R. , Lessler Justin 
Published: July 2020

AbstractSample size calculations are an essential component of the design and evaluation of scientific studies. However, there is a lack of clear guidance for determining the sample size needed for phylogenetic studies, which are becoming an essential part of studying pathogen transmission. We introduce a statistical framework for determining the number of true infector-infectee transmission pairs identified by a phylogenetic study, given the size and population coverage of that study. We then show how characteristics of the criteria used to determine linkage and aspects of the study design can influence our ability to correctly identify transmission links, in sometimes counterintuitive ways. We test the overall approach using outbreak simulations and provide guidance for calculating the sensitivity and specificity of the linkage criteria, the key inputs to our approach. The framework is freely available as the R package phylosamp, and is broadly applicable to designing and evaluating a wide array of pathogen phylogenetic studies.
Cell type-aware analysis of RNA-seq data
Authors: Jin Chong , Chen Mengjie , Lin Danyu , Sun Wei 
Published: July 2020

AbstractMost tissue samples are composed of different cell types. Differential expression analysis without accounting for cell type composition cannot separate the changes due to cell type composition or cell type-specific expression. We propose a computational framework to address these limitations:Cell TypeAware analysis ofRNA-seq(CARseq). CARseq employs a negative binomial distribution that appropriately models the count data from RNA-seq experiments. Simulation studies show that CARseq has substantially higher power than a linear model-based approach and it also provides more accurate estimate of the rankings of differentially expressed genes. We have applied CARseq to compare gene expression of schizophrenia/autism subjects versus controls, and identified the cell types underlying the difference and similarities of these two neuron-developmental diseases. Our results are consistent with the results from differential expression analysis using single cell RNA-seq data.
Single-nucleotide conservation state annotation of the SARS-CoV-2 genome
Authors: Kwon Soo Bin , Ernst Jason 
Published: July 2020

AbstractGiven the global impact and severity of COVID-19, there is a pressing need for a better understanding of the SARS-CoV-2 genome and mutations. Multi-strain sequence alignments of coronaviruses (CoV) provide important information for interpreting the genome and its variation. We apply a comparative genomics method, ConsHMM, to the multi-strain alignments of CoV to annotate every base of the SARS-CoV-2 genome with conservation states based on sequence alignment patterns among CoV. The learned conservation states show distinct enrichment patterns for genes, protein domains, and other regions of interest. Certain states are strongly enriched or depleted of SARS-CoV-2 mutations, which can be used to predict potentially consequential mutations. We expect the conservation states to be a resource for interpreting the SARS-CoV-2 genome and mutations.
Biologic Drug Survival in Psoriasis: A Systematic Review & Comparative Meta-Analysis
Authors: Mourad A. I. , Gniadecki R. 
Published: July 2020

ABSTRACTBackgroundDrug survival studies have been utilized to evaluate the real-world effectiveness of biologics used in psoriasis. However, the increasing volume of drug survival data suffers from large variability due to regional differences in drug availability, patient selection and biologic reimbursement.ObjectivesTo conduct a meta-analysis of biologic drug survival to determine comparative effectiveness of the biologics in a real-world setting.MethodsStudies reporting drug survival for biologic therapy in psoriasis were identified by a systematic literature search. Hazard ratio data for drug discontinuation were estimated directly from published Kaplan-Meier estimator curves at year 1, 2 and 5 of treatment and compared pairwise for the following biologics: ustekinumab, adalimumab, etanercept, infliximab, secukinumab and ixekizumab. This pooled hazard ratios were used to estimate 2- and 5-year overall drug survival rates.ResultsUstekinumab had the longest persistence at 2 years and 5 years among all biologics included in this meta-analysis. Adalimumab was superior to etanercept and infliximab at 5 years. Pooled 5-year drug survival rates for adalimumab, etanercept, and infliximab were 46.3%, 35.9% and 34.7%, respectively. 2- and 5-year data were not available for anti-IL-17 drugs, but at 1-year ustekinumab outperformed secukinumab, the latter being equal to anti-TNFs.ConclusionsUstekinumab is characterized by longer drug survival than TNF inhibitors and IL-17 inhibitors. Estimated pooled 2- and 5-year drug survival rates may serve as a useful tool for patient communication and clinical decision-making.
Clinical Electroencephalography Findings and Considerations in Hospitalized Patients with Coronavirus SARS-CoV-2
Authors: Ayub Neishay , Cohen Joseph , Jing Jin , Jain Aayushee , Tesh Ryan , Mukerji Shibani S. , Zafar Sahar F. , Westover M. Brandon , Kimchi Eyal Y. 
Published: July 2020

AbstractBackground and PurposeReports have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes neurologic manifestations including encephalopathy and seizures. However, there has been relatively limited electrophysiology data to contextualize these specific concerns and to understand their associated clinical factors. Our objective was to identify EEG abnormalities present in patients with SARS-CoV-2, and to determine whether they reflect new or preexisting brain pathology.MethodsWe studied a consecutive series of hospitalized patients with SARS-CoV-2 who received an EEG, obtained using tailored safety protocols. Data from EEG reports and clinical records were analyzed to identify EEG abnormalities and possible clinical associations, including neurologic symptoms, new or preexisting brain pathology, and sedation practices.ResultsWe identified 37 patients with SARS-CoV-2 who underwent EEG, of whom 14 had epileptiform findings (38%). Patients with epileptiform findings were more likely to have preexisting brain pathology (6/14, 43%) than patients without epileptiform findings (2/23, 9%; p=0.042). There were no clear differences in rates of acute brain pathology. One case of nonconvulsive status epilepticus was captured, but was not clearly a direct consequence of SARS-CoV-2.Abnormalities of background rhythms were common, and patients recently sedated were more likely to lack a posterior dominant rhythm (p=0.022).ConclusionsEpileptiform abnormalities were common in patients with SARS-CoV-2 referred for EEG, but particularly in the context of preexisting brain pathology and sedation. These findings suggest that neurologic manifestations during SARS-CoV-2 infection may not solely relate to the infection itself, but rather may also reflect patients’ broader, preexisting neurologic vulnerabilities.
Development and large-scale validation of a highly accurate SARS-COV-2 serological test using regular test strips for autonomous and affordable finger-prick sample collection, transportation, and storage
Authors: Alvim Renata G. F. , Lima Tulio M. , Rodrigues Danielle A. S. , Marsili Federico F. , Bozza Vicente B. T. , Higa Luiza M. , Monteiro Fabio L. , Abreu Daniel P. B. , Leitão Isabela C. , Carvalho Renato S. , Galliez Rafael M. , Castineiras Terezinha M. P. P. , Travassos Leonardo H. , Nobrega Alberto , Tanuri Amilcar , Ferreira Orlando C. , Castilho Leda R. , Vale André M. 
Published: July 2020

AbstractAccurate serological tests are essential tools to allow adequate monitoring and control of COVID-19 spread. Production of a low-cost and high-quality recombinant viral antigen can enable the development of reliable and affordable serological assays, which are urgently needed to facilitate epidemiological surveillance studies in low-income economies. Trimeric SARS-COV-2 spike (S) protein was produced in serum-free, suspension-adapted HEK293 cells. Highly purified S protein was used to develop an ELISA, named S-UFRJ test. It was standardized to work with different types of samples: (i) plasma or serum from venous blood samples; (ii) eluates from dried blood spots (DBS) obtained by collecting blood drops from a finger prick. We developed a cost-effective, scalable technology to produce S protein based on its stable expression in HEK293 cells. Using this recombinant antigen, we presented a workflow for test development in the setting of a pandemic, starting from limited amounts of samples up to reaching final validation with hundreds of samples. Test specificity was determined to be 98.6%, whereas sensitivity was 95% for samples collected 11 or more days after symptoms onset. A ROC analysis allowed optimizing the cut-off and confirming the high accuracy of the test. Endpoint titers were shown to correlate with virus neutralization assessed as PRNT90. There was excellent agreement between plasma and DBS samples, significantly simplifying sample collection, storing, and shipping. An overall cost estimate revealed that the final retail price could be in the range of one US dollar. The S-UFRJ assay developed herein meets the quality requirements of high sensitivity and specificity. The low cost and the use of mailable DBS samples allow for serological surveillance and follow-up of SARS-CoV-2 vaccination of populations regardless of geographical and socio-economic aspects. We hope the detailed guidelines for the development of an affordable and accurate anti-spike SARS-COV-2 ELISA, such as S-UFRJ described here, will stimulate governmental and non-governmental health agencies in other countries to engage in much-needed large-scale studies monitoring the spread and immunity to SARS-COV-2 infection.
Inequalities in air pollution exposure are increasing in the United States
Authors: Jbaily Abdulrahman , Zhou Xiaodan , Liu Jie , Lee Ting-Hwan , Verguet Stéphane , Dominici Francesca 
Published: July 2020

AbstractExposure to ambient air pollution contributes substantially to the global burden of disease, and in 2015, ambient exposure to PM2.5 (fine particles with a mass median aerodynamic diameter of less than 2.5 μm) was the fifth-ranking risk factor of mortality globally. We analyzed data from the US zip code tabulation areas (N=32047) for 2000-2016 and found strong evidence of inequalities in exposure to PM2.5 among both racial/ethnic and income groups. Most alarming, we found that these inequalities have been increasing over time. From 2010 to 2016 inequalities in the exposure to PM2.5 levels above 8 μg/m3 across racial/ethnic, and income groups increased by factors of 1.6 and 4.0 respectively. As shown in our powerful map visualizations, these results indicate that air pollution regulations must not only decrease PM2.5 concentration levels nationwide but also prioritize reducing environmental injustice across the US.
Replication assessment of NUS1 variants in Parkinson’s Disease
Authors: Bustos Bernabe I. , Bandres-Ciga Sara , Gibbs J. Raphael , Krainc Dimitri , Mencacci Niccolo E. , Gan-Or Ziv , Lubbe Steven J. ,   for the International Parkinson’s Disease Genomics Consortium (IPDGC).
Published: July 2020

AbstractThe NUS1 gene was recently associated with Parkinson’s disease (PD) in the Chinese population. Here, as part of the International Parkinson’s Disease Genomics Consortium (IPDGC), we have leveraged large-scale PD case-control cohorts to comprehensively assess the NUS1 association in individuals of European descent. Burden analysis of rare nonsynonymous damaging variants across case-control individuals from whole-exome and -genome datasets did not find evidence of NUS1 association with PD. Overall, single variant tests for rare (MAF<0.01) and common (MAF>0.01) variants, including 15 PD-GWAS cohorts and summary statistics from the largest PD GWAS meta-analysis to date, also did not uncover any associations. Our results indicate a lack of evidence for a role of rare damaging nonsynonymous NUS1 variants in PD in unrelated case-control cohorts of European descent, suggesting that the previously observed association could be driven by extremely rare population-specific variants.
Long Term Safety and Efficacy of Sub-Lingual Ketamine Troches / Lozenges in Chronic Non-Malignant Pain Management
Authors: Maudlin Ben , Gibson Stephen B. , Aggarwal Arun 
Published: July 2020

ABSTRACTIntroductionChronic non-malignant pain is a disabling condition that results in a reduction in function and quality of life when inadequately managed. Sub-lingual ketamine has been shown to be efficacious for use in chronic pain. Despite its use for decades in chronic non-malignant pain, there is no published long-term data on safety, side effects or adverse drug reactions. The aim of this case-series is to provide the initial evidence for safety and efficacy in this patient group.MethodsWe present a retrospective review of twenty-nine patients (n=29) from a metropolitan tertiary pain service who have been receiving sub-lingual ketamine troches / lozenges between the period of 2012-2019. Patients were identified from the outpatient pain clinic, who had been admitted for inpatient subcutaneous ketamine infusions as part of opiate detoxification or management of central sensitisation due to a chronic neuropathic pain syndrome. An initial review was performed to check the patient started taking the ketamine troches. Each of these medical records was reviewed manually to extract information to a datasheet.ResultsThere was a wide range of dosages used from 25-600mg in divided doses. The duration of treatment ranged from 2-89 months. There was no association with either the dosage or duration of treatment and frequency of side effects. There was an overall reduction in the use of opioids, gabapentinoids or benzodiazepines in 59% of patients with 39% having a complete cessation of an analgesic agent. Side effects were reported in 24%, but only 7% discontinued the treatment due to the side effect (drowsiness). There were no reports of renal impairment, cystitis, or hepatotoxicity.DiscussionThis retrospective case-series has demonstrated that sub-lingual ketamine is a safe and effective analgesic agent to use in chronic non-malignant pain management. It is indicated in a variety of chronic pain conditions and has an excellent safety profile, with no association between the frequency in side effects and duration of therapy or total daily dosages. The study has also shown that the “safe” dose may be higher than the previous consensus.Contribution StatementA.A and S.G. recruited the patients. A.A. & B.M. created the parameters for the data collection sheet. B.M Collected most of the data from the medical records, entered it into a datasheet, wrote the manuscript, ran the statistics, performed the data analysis, and generated the figures and tables. A.A. Edited the manuscript. S.G. and A.A were the research supervisors.
Low genetic diversity in a population of Tricolored Blackbird (Agelaius tricolor), a species pending Endangered status
Authors: Liu Irene A. , Meese Robert J. 
Published: July 2020

ABSTRACTThe Tricolored Blackbird (Agelaius tricolor) is a colonial songbird, found almost exclusively in California, whose total population size has sharply declined over the past century. It is currently under review to be listed as Endangered under both the California and U.S. Endangered Species Acts. Here we assess the genetic diversity of a breeding population in California’s Central Valley, comparing our findings with previously sampled conspecific and congeneric populations. First, we genotyped 50 adults at 9 microsatellite loci in our focal population and estimated allelic and Shannon diversity, observed and expected heterozygosity, and the inbreeding coefficient (FIS). Second, we compared our results to those of the one existing study on Tricolored Blackbird conservation genetics and found that levels of allelic diversity and heterozygosity in our focal population were similar to those of 11 previously studied populations. Unlike the earlier study, which found moderately high mean inbreeding coefficients, we detected no evidence of inbreeding in our focal population. Third, we used 7 of the 9 loci to compare the genetic diversity of our focal population with populations of 2 previously sampledAgelaiuscongeners. We found that allelic diversity, Shannon diversity, and expected heterozygosity in our Tricolored Blackbird population were most similar to those of an isolated Red-winged Blackbird (A. phoeniceus) population in the Bahamas. We discuss possible reasons for the different results from the conspecific study, outline why the collective findings from both studies support the need for protective measures, and urge conservation action to maintain existing genetic diversity and gene flow before ongoing population losses lead to adverse fitness consequences.
Genetic architecture of 11 abdominal organ traits derived from abdominal MRI using deep learning
Authors: Liu Yi , Basty Nicolas , Whitcher Brandon , Bell Jimmy D , Sorokin Elena , van Bruggen Nick , Thomas E. Louise , Cule Madeleine 
Published: July 2020

AbstractCardiometabolic diseases are an increasing global health burden. While well established socioeconomic, environmental, behavioural, and genetic risk factors have been identified, our understanding of the drivers and mechanisms underlying these complex diseases remains incomplete. A better understanding is required to develop more effective therapeutic interventions. Magnetic resonance imaging (MRI) has been used to assess organ health in a number of studies, but large-scale population-based studies are still in their infancy. Using 38,683 abdominal MRI scans in the UK Biobank, we used deep learning to systematically quantify parameters from individual organs (liver, pancreas, spleen, kidneys, lungs and adipose depots), and demonstrate that image derived phenotypes (volume, fat and iron content) reflect organ health and disease. We show that these traits have a substantial heritable component (8%-44%), and identify 93 independent genome-wide significant associations, including 3 associations with liver fat and one with liver iron that have not previously been reported, and 73 in traits that have not previously been studied. Overall our work demonstrates the utility of deep learning to systematically quantify health parameters from high-throughput MRI across a range of organs and tissues of the abdomen, and to generate new insights into the genetic architecture of complex traits.
Species packing and the latitudinal gradient in beta-diversity
Authors: Cao Ke , Condit Richard , Mi Xiangcheng , Chen Lei , Ren Haibao , Xu Wubing , Burslem David F. R. P. , Cai Chunrong , Cao Min , Chang Li-Wan , Chu Chengjin , Cui Fuxin , Du Hu , Ediriweera Sisira , Gunatilleke C.S.V. , Gunatilleke I.U.A.N. , Hao Zhanqing , Jin Guangze , Li Jinbo , Li Buhang , Li Yide , Liu Yankun , Ni Hongwei , O’Brien Michael J. , Qiao Xiujuan , Shen Guochun , Tian Songyan , Wang Xihua , Xu Han , Xu Yaozhan , Yang Libing , Yap Sandra L. , Lian Juyu , Ye Wanhui , Yu Mingjian , Su Sheng-Hsin , Chang-Yang Chia-Hao , Guo Yili , Li Xiankun , Zeng Fuping , Zhu Daoguang , Zhu Li , Sun I-Fang , Ma Keping , Svenning Jens-Christian 
Published: July 2020

AbstractThe decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide here a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogs. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographic heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.