bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in COVID-19 mortality across Michigan, United States
Authors: Parpia Alyssa S. , Pandey Abhishek , Martinez Isabel , El-Sayed Abdulrahman M. , Wells Chad R. , Myers Lindsey , Duncan Jeffrey , Collins Jim , Fitzpatrick Meagan C. , Galvani Alison P. 
Published: December 2020

AbstractBlack populations in the US are disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and demographic characteristics is not well understood. We evaluated COVID-19 mortality in Michigan using individual-level death certificate and surveillance data from the Michigan Department of Health and Human Services from March 16 to October 26, 2020. Among the 6,065 COVID-19-related deaths, Black individuals experienced 3.6 times the mortality rate as White individuals. Black individuals under 65 years without comorbidities had a mortality rate 12.6 times that of their White counterparts. After accounting for age, sex, and comorbidities, we found that Black individuals in all strata are at higher risk of COVID-19 mortality than their White peers. We demonstrate that inequities in mortality are driven by ongoing systemic racism, as opposed to comorbidity burden or older age, and further highlight how underlying disparities across the race are compounded in crises.
The PAX1 locus at 20p11 is a modifier for bilateral cleft lip only
Authors: Curtis Sarah W. , Chang Daniel , Lee Myoung Keun , Shaffer John R. , Indencleef Karlijne , Epstein Michael P. , Cutler David J. , Murray Jeffrey C. , Feingold Eleanor , Beaty Terri H. , Claes Peter , Weinberg Seth M. , Marazita Mary L. , Carlson Jenna C. , Leslie Elizabeth J. 
Published: December 2020

AbstractNonsyndromic orofacial clefts (OFCs) are the most common craniofacial birth defect in humans and, like many complex traits, OFCs are phenotypically and etiologically heterogenous. The phenotypic heterogeneity of OFCs extends beyond the structures affected by the cleft (e.g., cleft lip (CL) and cleft lip and palate (CLP) to other features, such as the severity of the cleft. Here, we focus on bilateral and unilateral clefts as one dimension of OFC severity. Unilateral clefts are more frequent than bilateral clefts for both CL and CLP, but the genetic architecture of these subtypes is not well understood, and it is not known if genetic variants predispose for the formation of one subtype over another. Therefore, we tested for subtype-specific genetic associations in 44 bilateral CL (BCL) cases, 434 unilateral CL (UCL) cases, 530 bilateral CLP cases (BCLP), 1123 unilateral CLP (UCLP) cases, and unrelated controls (N = 1626), using the mixed-model approach implemented in GENESIS. While no novel loci were found in subtype-specific analyses comparing cases to controls, the genetic architecture of UCL was distinct compared to BCL, with 43.8% of suggestive loci (p < 1.0×10−5) having non-overlapping confidence intervals between the two subtypes. To further understand the genetic risk factors for severity differences, we then performed a genome-wide scan for modifiers using a similar mixed-model approach and found one genome-wide significant modifier locus on 20p11 (p = 7.53×10−9), 300kb downstream of PAX1, associated with higher odds of BCL compared to UCL, which also replicated in an independent cohort (p = 0.0018) and showed no effect in BCLP (p>0.05). We further found that SNPs at this locus were associated with normal human nasal shape. Taken together, these results suggest bilateral and unilateral clefts may have differences in their genetic architecture, especially between CL and CLP. Moreover, our results suggest BCL, the rarest form of OFC, may be genetically distinct from the other OFC subtypes. This expands our understanding of genetic modifiers for subtypes of OFCs and further elucidates the genetic mechanisms behind the phenotypic heterogeneity in OFCs.
Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission
Authors: Larremore Daniel B. , Toomre Derek , Parker Roy 
Published: December 2020

AbstractA central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Molecular tests that detect viral RNAs or antigens will be unable to rise to this challenge unless testing capacity increases by at least an order of magnitude while decreasing turnaround times. Here, we evaluate an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections—including those with no other symptoms—when a standardized olfaction test is used. We model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction. We find that monitoring olfactory dysfunction could reduce spread via regular screening, and could reduce risk when used at point-of-entry for single-day events. In light of these estimated impacts, and because olfactory tests can be mass produced at low cost and self-administered, we suggest that screening for olfactory dysfunction could be a high impact and cost-effective method for broad COVID-19 screening and surveillance.
Rapid and accurate point-of-care testing for SARS-CoV2 antibodies
Authors: Esmail Sally , Knauer Michael J. , Abdoh Husam , Chin-Yee Benjamin , Stogios Peter , Seitova Almagul , Hutchinson Ashley , Yusifov Farhad , Skarina Tatiana , Evdokimova Elena , Ackloo Suzanne , Lowes Lori , Voss Courtney , Hedley Benjamin D. , Bhayana Vipin , Chin-Yee Ian , Li Shawn S-C. 
Published: December 2020

ABSTRACTThe COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has grown into worst public health crisis since the 1918 influenza pandemic. As COVID-19 continues to spread around the world, there is urgent need for a rapid, yet accurate antibody test to identify infected individuals in populations to inform health decisions. We have developed a rapid, accurate and cost-effective serologic test based on antibody-dependent agglutination of antigen-coated latex particles, which uses ∼5 µl plasma and takes <5 min to complete with no instrument required. The simplicity of this test makes it ideal for point-of-care (POC) use at the community level. When validated using plasma samples that are positive or negative for SARS-CoV-2, the agglutination assay detected antibodies against the receptor-binding domain of the spike (S-RBD) or the nucleocapsid (N) protein of SARS-CoV-2 with 100% specificity and ∼98% sensitivity. Furthermore, we found that the strength of the S-RBD antibody response measured by the agglutination assay correlated with the efficiency of the plasma in blocking RBD binding to the angiotensin converting enzyme 2 (ACE2) in a surrogate neutralization assay, suggesting that the agglutination assay may be used to identify individuals with virus-neutralizing antibodies. Intriguingly, we found that >92% of patients had detectable antibodies on the day of positive viral RNA test, suggesting that seroconversion may occur earlier than previously thought and that the agglutination antibody test may complement RNA testing for POC diagnosis of SARS-CoV-2 infection.
Estimated prevalence of dental fear in adults: a systematic review and meta-analysis
Authors: Silveira Ethieli R. , Cademartori Mariana G. , Schuch Helena S. , Armfield Jason M. , Demarco Flavio F. 
Published: December 2020

ABSTRACTObjectivesTo systematically review the literature on the prevalence of dental fear in adults to estimate a worldwide pooled prevalence and to investigate factors related to the heterogeneity of estimates.MethodsInclusion criteria were population-based studies reporting the prevalence or data that allowed the calculation of prevalence of dental fear in adults and/or elders. Five electronic databases (Embase, PubMed, Scopus, Virtual Health Library (BVS) and Web of Science) were searched. Two researchers independently performed the study selection, data extraction and quality assessment of the included studies. The prevalence pooled estimates of dental fear were calculated using fixed- and random-effect models. Subgroup analyses were performed to investigate variability between studies.ResultsThe search strategy identified 4,486 studies. After removal of duplicates (1,722), title and abstract screening (2,764) and full-text reading (108), 31 publications were deemed eligible for this systematic review. A total of 72,577 individuals 18 years of age or older composed the sample of this systematic review. The global estimated prevalence of dental fear and anxiety (DFA), high DFA and severe DFA in adults were 13.8%, 11.2% and 2.6%, respectively. Subgroup analyses showed a higher prevalence of DFA, high DFA and severe DFA among women and younger adults. The instrument used to measure dental fear also affected the prevalence of the outcome.ConclusionsDental fear and high dental fear are prevalent in adults worldwide, being more prevalent among women.
Development and validation of automated computer aided-risk score for predicting the risk of in-hospital mortality using first electronically recorded blood test results and vital signs for COVID-19 hospital admissions: a retrospective development and validation study
Authors: Faisal Muhammad , Mohammed Mohammed A , Richardson Donald , Fiori Massimo , Beatson Kevin 
Published: December 2020

AbstractObjectivesThere are no established mortality risk equations specifically for unplanned emergency medical admissions which include patients with the novel coronavirus SARS-19 (COVID-19). We aim to develop and validate a computer-aided risk score (CARMc19) for predicting mortality risk by combining COVID-19 status, the first electronically recorded blood test results and latest version of the National Early Warning Score (NEWS2).DesignLogistic regression model development and validation study using a cohort of unplanned emergency medical admissions to hospital.SettingYork Hospital (YH) as model development dataset and Scarborough Hospital (SH) as model validation dataset.ParticipantsUnplanned adult medical admissions discharged over three months (11 March 2020 to 13 June 2020) from two hospitals (YH for model development; SH for external model validation) based on admission NEWS2 electronically recorded within ±24 hours and/or blood test results within ±96 hours of admission. We used logistic regression modelling to predict the risk of in-hospital mortality using two models: 1) CARMc19_N: age + sex + NEWS2 including subcomponents + COVID19; 2) CARMc19_NB: CARMc19_N in conjunction with seven blood test results and acute kidney injury score. Model performance was evaluated according to discrimination (c-statistic), calibration (graphically), and clinical usefulness at NEWS2 thresholds of 4+, 5+, 6+.ResultsThe risk of in-hospital mortality following emergency medical admission was similar in development and validation datasets (8.4% vs 8.2%). The c-statistics for predicting mortality for Model CARMc19_NB is better than CARMc19_N in the validation dataset (CARMc19_NB = 0.88 (95%CI 0.86 to 0.90) vs CARMc19_N = 0.86 (95%CI 0.83 to 0.88)). Both models had good internal and external calibration (CARMc19_NB: 1.01 (95%CI 0.88 vs 1.14) & CARMc19_N: 0.95 (95%CI 0.83 to 1.06)). At all NEWS2 thresholds (4+, 5+, 6+) model CARMc19_NB had better sensitivity and similar specificity.ConclusionsWe have developed a validated CARMc19 score with good performance characteristics for predicting the risk of in-hospital mortality following an emergency medical admission using the patient’s first, electronically recorded vital signs and blood tests results. Since the CARMc19 scores place no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure.
Brief Report: Sensory processing phenotypes in Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability
Authors: Lyons-Warren Ariel M , McCormack Maria C , Holder J. Lloyd 
Published: December 2020

AbstractSensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASD). Significant work has been done to characterize and classify specific sensory profiles in non-syndromic Autism. However, it is not known if syndromic Autism disorders such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID) have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding the underlying mechanisms of the disorders. In this manuscript we use the Short Sensory Profile-2 to characterize sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID and compare their responses to both expected results for typically developing children and published sensory profiles for non-syndromic ASD.
Early prediction of impending septic shock in children using age-adjusted Sepsis-3 criteria
Authors: Liu Ran , Greenstein Joseph L. , Fackler James C. , Bergmann Jules , Bembea Melania M. , Winslow Raimond L. 
Published: December 2020

AbstractSepsis is a syndrome which afflicts both adults and children, with many disease courses and diverse outcomes. Understanding of sepsis pathophysiology has changed over time; the Sepsis-3 criteria define sepsis in adults as organ dysfunction, quantified by SOFA score, caused by dysregulated immune response to infection. However, pediatric consensus definitions still utilize the SIRS-based Sepsis-2 criteria, though individual groups have attempted to adapt the Sepsis-3 criteria for children. We evaluate age-adjusted Sepsis-3 criteria on 2,384 pediatric patients admitted to the Johns Hopkins PICU, and apply previously-published methods for early prediction of septic shock. We obtain best early prediction performance of 0.96 AUC, 49.9% overall PPV, and a 5.8-hour median EWT using Sepsis-3 labels based on age-adjusted SOFA score. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children, and are able to stratify pediatric sepsis patients using their first post-threshold-crossing risk score.
Macrophage aggresome-like induced structures are flexible organizing platforms for immune signaling
Authors: Charbonneau Marie-Eve , Raghunathan Vedhika , O’Riordan Mary X.D. 
Published: December 2020

ABSTRACTMacrophages adopt a pro-inflammatory phenotype in response to environmental challenges in a process that often coincides with the formation of transient cytosolic p62/SQSTM1 inclusions containing ubiquitinated proteins in structures known as aggresome-like induced structures (ALIS). Although described as stress-induced inclusions that accumulate aggregated proteins, little direct evidence supports their hypothesized structural role in the context of immune stimulation. Here, we showed that these structures in primary macrophages are induced by multiple microbialbased ligands, including exposure to cytosolic double-stranded DNA. Rather than accumulating aggregated proteins, we observed that ubiquitinated proteins form a ring-shaped structure around the perimeter of these circular foci. We identified that different microbial stimuli induced the formation of ubiquitin-positive foci with distinct characteristics and we observed selective recruitment of context-dependent immune regulators. Our findings are consistent with a model where these ubiquitin-containing structures act as adaptable organizing centers for innate immune signaling.SUMMARYCharbonneau et al. demonstrate that ubiquitin- and p62-containing cytosolic ring-shaped structures induced by bacterial infections, microbial ligands and cytosolic double-stranded DNA contain context-dependent immune regulators, revealing an important insight on the cellular architecture required to coordinate signal transduction in macrophage.
Thede novogenome of the “Spanish” slugArion vulgarisMoquin-Tandon, 1855 (Gastropoda: Panpulmonata): massive expansion of transposable elements in a major pest species
Authors: Chen Zeyuan , Doğan Özgül , Guiglielmoni Nadège , Guichard Anne , Schrödl Michael 
Published: December 2020

AbstractBackgroundThe “Spanish” slug,Arion vulgarisMoquin-Tandon, 1855, is considered to be among the 100 worst pest species in Europe. It is common and invasive to at least northern and eastern parts of Europe, probably benefitting from climate change and the modern human lifestyle. The origin and expansion of this species, the mechanisms behind its outstanding adaptive success and ability to outcompete other land slugs are worth to be explored on a genomic level. However, a high-quality chromosome-level genome is still lacking.FindingsThe final assembly ofA. vulgariswas obtained by combining short reads, linked reads, Nanopore long reads, and Hi-C data. The genome assembly size is 1.54 Gb with a contig N50 length of 8.6 Mb. We found a recent expansion of transposable elements (TEs) which results in repetitive sequences accounting for more than 75% of theA. vulgarisgenome, which is the highest among all known gastropod species. We identified 32,518 protein coding genes, and 2,763 species specific genes were functionally enriched in response to stimuli, nervous system and reproduction. With 1,237 single-copy orthologs fromA. vulgarisand other related mollusks with whole-genome data available, we reconstructed the phylogenetic relationships of gastropods and estimated the divergence time of stylommatophoran land snails (Achatina) andArionslugs at around 126 million years ago, and confirmed the whole genome duplication event shared by them.ConclusionsTo our knowledge, theA. vulgarisgenome is the first land slug genome assembly published to date. The high-quality genomic data will provide valuable genetic resources for further phylogeographic studies ofA. vulgarisorigin and expansion, invasiveness, as well as molluscan aquatic-land transition and shell formation.
Freeze-frame imaging of dendritic calcium signals with TubuTag
Authors: Perez-Alvarez Alberto , Huhn Florian , Dürst Céline D. , Franzelin Andreas , Lamothe-Molina Paul , Oertner Thomas G. 
Published: December 2020

AbstractThe extensive dendritic arbor of neurons is thought to be actively involved in the processing of information. Dendrites contain a rich diversity of ligand- and voltage-activated ion channels as well as metabotropic receptors. In addition, they are capable of releasing calcium from intracellular stores. Under specific conditions, large neurons produce calcium spikes that are locally restricted to a dendritic section. To investigate calcium signaling in dendrites, we introduce TubuTag, a genetically encoded calcium sensor anchored to the cytoskeleton. TubuTag integrates cytoplasmic calcium signals by irreversible photoconversion from green to red fluorescence when illuminated with violet light. To image the mm-long dendritic tree of pyramidal neurons at subcellular resolution, we used a custom two-photon microscope with a large field of view. As the read-out of fluorescence can be performed several hours after photoconversion, TubuTag will help investigating dendritic signal integration and calcium homeostasis in large populations of neurons.
Using big data to estimate whale watching effort
Authors: Almunia Javier , Delponti Patricia , Rosa Fernando 
Published: December 2020

ABSTRACTThe growing concerns about the negative effects caused by whale watching on wild The growing concerns about the negative effects caused by whale watching on wild cetacean populations are evincing the need to measure whale watching effort more precisely. The current alternatives do not provide sufficient information or imply time-consuming and staff intensive tasks that limit their effectiveness to establish the maximum carrying capacity for this touristic activity. A methodology based on big data analysis, using Automatic Information System (AIS) messages, can provide valuable vessel activity information, which is necessary to estimate whale watching effort on cetacean populations. We used AIS data to automatically detect whale watching operations and quantify whale watching effort with high spatial and temporal resolution in the Canary Islands. The results obtained in this study are very encouraging, proving that the methodology is able to estimate seasonal and annual trends in the whale watching effort. The methodology has also proved to be effective in providing detailed spatial information about the whale watching effort, which makes an interesting tool to manage spatial regulations and enforce exclusion zones. The widespread use of AIS devices in maritime navigation provides an enormous potential to easily extend this methodology to other regions worldwide. Any public strategy aimed at the sustainable use of the marine resources should enhance the use of this kind of information technologies, collecting and archiving detailed information on the activity of all the vessels, especially in marine protected areas.
Balanced Functional Module Detection in Genomic Data
Authors: Tritchler David , Towle-Miller Lorin M , Miecznikowski Jeffrey C 
Published: December 2020

AbstractHigh dimensional genomic data can be analyzed to understand the effects of multiple variables on a target variable such as a clinical outcome, risk factor or diagnosis. Of special interest are functional modules, cooperating sets of variables affecting the target. Graphical models of various types are often useful for characterizing such networks of variables. In other applications such as social networks, the concept of balance in undirected signed graphs characterizes the consistency of associations within the network. To extend this concept to applications where a set of predictor variables influences an outcome variable, we define balance for functional modules. This property specifies that the module variables have a joint effect on the target outcome with no internal conflict, an efficiency that evolution may use for selection in biological networks. We show that for this class of graphs, observed correlations directly reflect paths in the underlying graph. Consequences of the balance property are exploited to implement a new module discovery algorithm, bFMD, which selects a subset of variables from highdimensional data that compose a balanced functional module. Our bFMD algorithm performed favorably in simulations as compared to other module detection methods that do not consider balance properties. Additionally, bFMD detected interpretable results in a real application for RNA-seq data obtained from The Cancer Genome Atlas (TCGA) for Uterine Corpus Endometrial Carcinoma using the percentage of tumor invasion as the target outcome of interest. bFMD detects sparse sets of variables within highdimensional datasets such that interpretability may be favorable as compared to other similar methods by leveraging balance properties used in other graphical applications.