bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Value of Symptoms for Pediatric SARS-CoV-2 Infection in a Primary Care Setting
Authors: Weng Chien-Hsiang , Butt Wesley Wing Wah , Brooks Meredith B. , Clarke Claudia , Jenkins Helen E. , Holland Sabina D. , Chiang Silvia S. 
Published: March 2021

AbstractPurposeTo evaluate the diagnostic value of symptoms used in the screening approaches by daycares and schools for identifying children and adolescents with possible SARS-CoV-2 infection, we designed a large observational study utilizing the data from primary care settings.MethodsThis cohort study included children and adolescents evaluated in a network of clinics in Rhode Island. Participants were age-stratified: 0-4, 5-11, and 12-17 years. We estimated the sensitivity, specificity, and area under the receiver operating curve (AUC) of individual symptoms and three symptom combinations: a probable case definition published by the Rhode Island Department of Health (RIDOH), and two novel combinations generated by different statistical approaches to maximize sensitivity and AUC. We evaluated the test characteristics of symptom combinations both with and without consideration of COVID-19 exposure.ResultsTwo-hundred seventeen (39.1%) of 555 participants were SARS-CoV-2-infected. Fever was more common among 0-4 years-olds (p=0.002); older children more frequently reported fatigue (p=0.02) and anosmia or ageusia (p=0.047). In children >5 years old, anosmia or ageusia had 94-98% specificity. In all age groups, exposure history most accurately predicted infection. In combination with COVID-19 exposure history, various symptom combinations had sensitivity >95% but specificity <30%. No individual symptom or symptom combination had AUC ≥0.70.ConclusionsAnosmia or ageusia in children ≥5 years old and dyspnea in children 5-11 years old should raise providers’ index of suspicion for COVID-19. However, our overall findings underscore the limited diagnostic value of symptoms and the critical need for widely available, efficient testing.
Modeling High-grade serous ovarian carcinoma using a combination ofin vivoelectroporation and CRISPR/Cas9 mediated genome editing
Authors: Teng Katie , Ford Mathew , Harwalkar Keerthana , Li YuQi , Farnell David , Yamanaka Nobuko , Tuyet Nhung Ton Nu , Huntsman David , Arseneau Jocelyne , Yamanaka Yojiro 
Published: March 2021

AbstractOvarian cancer remains the most lethal gynecological cancer today. High-grade serous ovarian carcinoma (HGSC) is the most common and lethal type of ovarian cancer and is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination ofin vivoelectroporation and CRISPR/Cas9 mediated genome editing. We mutated tumor suppressor genes associated with HGSC in two different combinations;Brca1, Tp53, Ptenwith/withoutLkb1and successfully generated HGSC, however, with different latencies and pathophysiology. By utilizing Cre lineage tracing in our system, we visualized peritoneal micrometastases in an immune-competent environment. Because our strategy is flexible in selecting mutation combinations and targeting areas, it would be useful for generating ovarian cancer mouse models.Significance StatementHigh grade serous ovarian cancer (HGSC) is the most common ovarian malignancy but our knowledge of early tumorigenesis is still quite limited due to late diagnosis of patients. We developed a new strategy of generating mouse ovarian cancer models using a combination of in vivo electroporation and CRISPR-mediated genome editing. We demonstrated that a combination of three tumor suppressor gene mutations (Brca1, Tp53 and Pten) is sufficient to develop HGSCs. Interesting, an additional mutation inLkb1drastically changed tumor latency, penetrance and pathophysiology through changing its cell-of-origin. Our strategy is highly flexible in selection of mutation combinations and targeting areas in immune competent mice and useful to study early tumorigenesis of ovarian cancer.
Taxonomic scale dependency of Bergmann’s patterns: A cross-scale comparison of hawkmoths and birds along a tropical elevational gradient
Authors: Mungee Mansi , Pandit Rohan , Athreya Ramana 
Published: March 2021

AbstractBergmann’s rule predicts a larger body size for endothermic organisms in colder environments. The multiplicity of patterns and processes is expected because body size and temperature are two most fundamental factors on which many physiological, ecological and evolutionary processes depend, affecting all levels of biological organization, from individuals to communities. The confounding results from previous studies may be due to the differences in taxonomic (intraspecific, interspecific and community) and spatial (latitudinal vs elevational) scales. We compared Bergmann’s patterns for endotherms (Aves) and ectotherms (Lepidoptera:Sphingidae) along a same 2.6 km elevational transect in the eastern Himalayas. Using a large data spanning 3,302 hawkmoths (76 morpho-species) and 15,746 birds (245 species), we compared the patterns at the intraspecific (hawkmoths only), interspecific and community scales. At the interspecific scale, we account for phylogenetic non-independence in body mass by using a heirarchical linear mixed effects model for hawkmoths, and a phylogenetic generalised least squares model for birds. We assess the importance of using abundance-weighted metrics at the community scales, after accounting for spatial auto-correlation in communities. Hawkmoths exhibited positive Bergmann’s pattern at the intraspecific and abundance-weighted community scale. Intraspecific variation accounted for a substantial 33% variation at the community level. Contrary to this, birds exhibited a strong converse-Bergmann’s pattern at interspecific and community scales, both with- and without-abundance. Overall, all metrics which incorporate local traits and/or species abundances show stronger correlations than when this information is lacking. The multiplicity of patterns at a single location provides the opportunity to disentangle the relative contribution of individual- and species-level processes by integrating data across multiple nested taxonomic scales for the same taxa. We suggest that future studies of Bergmann’s patterns should explicitly address taxonomic- and spatial-scale dependency, with species relative abundance and intraspecific trait variation as essential ingredients especially at short elevational scales.
Whole-genome-basedHelicobacter pylorigeographic surveillance: a visualized and expandable webtool
Authors: Jiang Xiaosen , Xu Zheng , Zhang Tongda , Li Yuan , Li Wei , Tan Hongdong 
Published: March 2021

AbstractHelicobacter pyloriexhibits specific geographic distributions that related to the clinical outcomes. Despite the high infection rate ofH. pylorithroughout the world, the genetic epidemiology surveillance ofH. pyloristill needs to be improved. Here, we used single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) that facilitates genomic population analyses ofH. pyloriand encourages the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 publicH. pylorigenomes were downloaded and used to construct the typing tool, named as HPTT (H. pyloriTyping Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolates source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main source of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their own dataset against the existing global database in an easy and rapid way, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tool and visualization tool. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary,H. pylorityping tool (HPTT) is a novel genomic epidemiological tool that can achieve high resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure analysis, evolution analysis and epidemiological surveillance ofH. pylori.
scAMACE: Model-based approach to the joint analysis of single-cell data on chromatin accessibility, gene expression and methylation
Authors: Wangwu Jiaxuan , Sun Zexuan , Lin Zhixiang 
Published: March 2021

AbstractThe advancement in technologies and the growth of available single-cell datasets motivate integrative analysis of multiple single-cell genomic datasets. Integrative analysis of multimodal single-cell datasets combines complementary information offered by single-omic datasets and can offer deeper insights on complex biological process. Clustering methods that identify the unknown cell types are among the first few steps in the analysis of single-cell datasets, and they are important for downstream analysis built upon the identified cell types. We propose scAMACE for the integrative analysis and clustering of single-cell data on chromatin accessibility, gene expression and methylation. We demonstrate that cell types are better identified and characterized through analyzing the three data types jointly. We develop an efficient expectation-maximization (EM) algorithm to perform statistical inference, and evaluate our methods on both simulation study and real data applications. We also provide the GPU implementation of scAMACE, making it scalable to large datasets. The software and datasets are available athttps://github.com/cuhklinlab/scAMACE_py(python implementation) andhttps://github.com/cuhklinlab/scAMACE(R implementation).
LKB1 inactivation modulates chromatin accessibility to drive metastatic progression
Authors: Pierce Sarah E. , Granja Jeffrey M. , Corces M. Ryan , Brady Jennifer J. , Tsai Min K. , Pierce Aubrey B. , Tang Rui , Chu Pauline , Feldser David M. , Chang Howard Y. , Bassik Michael C. , Greenleaf William J. , Winslow Monte M. 
Published: March 2021

AbstractMetastasis is the leading cause of cancer-related deaths, enabling cancer cells to expand to secondary sites and compromise organ function1. Given that primary tumors and metastases often share the same constellation of driver mutations2–4, the mechanisms driving their distinct phenotypes are unclear. Here, we show that inactivation of the frequently mutated tumor suppressor gene, liver kinase B1 (LKB1), has evolving effects throughout lung cancer progression, leading to the differential epigenetic re-programming of early-stage primary tumors compared to late-stage metastases. By integrating genome-scale CRISPR/Cas9 screening with bulk and single-cell multi-omic analyses, we unexpectedly identify LKB1 as a master regulator of chromatin accessibility in lung adenocarcinoma primary tumors. Using an in vivo model of metastatic progression, we further reveal that loss of LKB1 activates the early endoderm transcription factor SOX17 in metastases and a metastatic-like sub-population of cancer cells within primary tumors. SOX17 expression is necessary and sufficient to drive a second wave of epigenetic changes in LKB1-deficient cells that enhances metastatic ability. Overall, our study demonstrates how the downstream effects of an individual driver mutation can appear to change throughout cancer development, with implications for stage-specific therapeutic resistance mechanisms and the gene regulatory underpinnings of metastatic evolution.
Identification of biomarkers and pathways of mitochondria in sepsis patients
Authors: Yuan Gongsheng 
Published: March 2021

AbstractSepsis is a life-threatening condition associate with significant morbidity and mortality, but limited treatment. Mitochondria are recently recognized to be related to the pathophysiology of sepsis, and mitochondria could serve as a potential drug target. In our study, we aim to identify biological functions and pathways of mitochondria during the processes of sepsis by using a bioinformatics method to elucidate their potential pathogenesis. The gene expression profiles of the GSE167914 dataset were originally created by using the Nanostring nCounter Elements™ TagSet preselected for mitochondrial biogenesis and function panel. The biological pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), Gene Ontology (GO), and Reactome enrichment. KEGG and GO results showed the Neurodegeneration pathways such as Huntington and Parkinson pathways were mostly affected in the development of sepsis. Moreover, we identified several mitochondrial genes including TOMM40, TOMM20, TIMM22, TIMM10, TIMM17A, TIMM9, TIMM44 were involved in the regulation of protein translocation into mitochondria. Further, we predicted several regulators that had the ability to affect the mitochondria during sepsis by L1000fwd analysis. Thus, this study provides further insights into the mechanism of mitochondrial function during sepsis.
Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex
Authors: Herrero Jose L. , Smith Alexander , Mishra Akash , Markowitz Noah , Mehta Ashesh D. , Bickel Stephan 
Published: March 2021

AbstractThe progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent Theta Burst stimulation (iTBS), a form of electrical stimulation that mimics the natural brain activity patterns, has shown efficacy in inducing such effects in animal studies and rhythmic Transcranial Magnetic Stimulation (rTMS) studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans which could have implications for deep brain stimulation therapies. This study characterizes the physiological effects of cortical iTBS in the human cortex and compare them with single pulse alpha stimulation, another frequently used paradigm in rTMS research. We applied these stimulation paradigms to well-defined regions in the sensorimotor cortex which elicited contralateral hand or arm muscle contractions during electrical stimulation mapping in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using effective connectivity and beta oscillations coherence measures in areas connected to the treatment site as defined with cortico-cortical evoked potentials. Our results show that iTBS increases beta band synchronization within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta frequency band and the stimulation pattern (no effect was found with single-pulse alpha stimulation). The effects outlasted the stimulation by three minutes. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians and researchers to optimize brain stimulation protocols which may have translational value.
Dynamics of data availability in disease modeling: An example evaluating the trade-offs of ultra-fine-scale factors applied to human West Nile virus disease models in the Chicago area, USA
Authors: Uelmen J.A. , Irwin P. , Brown W.M. , Karki S. , Ruiz M.O. , Li B. , Smith R.L. 
Published: March 2021

AbstractBackgroundSince 1999, West Nile virus (WNV) has moved rapidly across the United States, resulting in tens of thousands of human cases. Both the number of human cases and the minimum infection rate (MIR) in vector mosquitoes vary across time and space and are driven by numerous abiotic and biotic forces, ranging from differences in microclimates to socio-demographic factors. Because the interactions among these multiple factors affect the locally variable risk of WNV illness, it has been especially difficult to model human disease risk across varying spatial and temporal scales. Cook and DuPage Counties, comprising the city of Chicago and surrounding suburbs, experience some of the highest numbers of human neuroinvasive cases of WNV in the United States. Despite active mosquito control efforts, there is consistent annual WNV presence, resulting in more than 285 confirmed WNV human cases and 20 deaths from the years 2014-2018 in Cook County alone.MethodsA previous Chicago-area WNV model identified the fifty-five most high and low risk locations in the Northwest Mosquito Abatement District (NWMAD), an enclave ¼ the size of the combined Cook and DuPage county area. In these locations, human WNV risk was stratified by model performance, as indicated by differences in studentized residuals. Within these areas, an additional two-years of field collections and data processing was added to a 12-year WNV dataset that includes human cases, MIR, vector abundance, and land-use, historical climate, and socio-economic and demographic variables, and was assessed by an ultra-fine-scale (1 km spatial × 1 week temporal resolution) multivariate logistic regression model.ResultsMultivariate statistical methods applied to the ultra-fine-scale model identified fewer explanatory variables while improving upon the fit of the previous model. Beyond MIR and climatic factors, efforts to acquire additional covariates only slightly improved model predictive performance.ConclusionsThese results suggest human WNV illness in the Chicago area may be associated with fewer, but increasingly critical, key variables at finer scales. Given limited resources, these findings suggest large variations in model performance occur, depending on covariate availability, and provide guidance in variable selection for optimal WNV human illness modeling.
Hybrid histidine kinase BinK repressesVibrio fischeribiofilm signaling at multiple developmental stages
Authors: Ludvik Denise A. , Bultman Katherine M. , Mandel Mark J. 
Published: March 2021

ABSTRACTThe symbiosis between the Hawaiian bobtail squid,Euprymna scolopes, and its exclusive light-organ symbiont,Vibrio fischeri, provides a natural system in which to study host-microbe specificity and gene regulation during the establishment of a mutually-beneficial symbiosis. Colonization of the host relies on bacterial biofilm-like aggregation in the squid mucus field. Symbiotic biofilm formation is controlled by a two-component signaling (TCS) system consisting of regulators RscS-SypF-SypG, which together direct transcription of the Syp symbiotic polysaccharide. TCS systems are broadly important for bacteria to sense environmental cues and then direct changes in behavior. Previously, we identified hybrid histidine kinase BinK as a strong negative regulator ofV. fischeribiofilm regulation, and here we further explore the function of BinK. To inhibit biofilm formation, BinK requires the predicted phosphorylation sites in both the histidine kinase (H362) and receiver (D794) domains. Furthermore, we show that RscS is not essential for host colonization whenbinKis deleted from strain ES114, and imaging of aggregate size revealed no benefit to the presence of RscS in a background lacking BinK. Strains lacking RscS still suffered in competition. Finally, we show that BinK functions to inhibit biofilm gene expression in the light organ crypts, providing evidence for biofilm gene regulation at later stages of host colonization. Overall, this study provides direct evidence for opposing activities of RscS and BinK and yields novel insights into biofilm regulation during the maturation of a beneficial symbiosis.IMPORTANCEBacteria are often in a biofilm state, and transitions between planktonic and biofilm lifestyles are important for pathogenic, beneficial, and environmental microbes. The critical nature of biofilm formation duringVibrio fischericolonization of the Hawaiian bobtail squid light organ provides an opportunity to study development of this processin vivousing a combination of genetic and imaging approaches. The current work refines the signaling circuitry of the biofilm pathway inV. fischeri, provides evidence that biofilm regulatory changes occur in the host, and identifies BinK as one of the regulators of that process. This study provides information about how bacteria regulate biofilm gene expression in an intact animal host.
Genome sequencing and functional genes comparison betweenSphingopyxisUSTB-05 andSphingomonas morindaeNBD5
Authors: Liu Chao , Xu Qianqian , Zhao Zhenzhen , Ahmad Shahbaz , Zhang Haiyang , Zhang Yufan , Pang Yu , Aikemu Abudumukeyiti , Liu Yang , Yan Hai 
Published: March 2021

ABSTRACTSphingomonadaceae has a large number of strains that can biodegrade hepatotoxins or environmental pollutants. The latest research reported that certain strains can also produce lutein. Based on the third-generation sequencing technology, we analyzed the whole genome sequence and compared related functional genes of two strains of Sphingomonadaceae isolated from different habitats. The genome ofSphingopyxisUSTB-05 was 4,679,489 bp and contained 4312 protein coding genes. The 4,239,716 bp nuclear genome ofSphingomonas morindaeNBD5, harboring 3882 protein coding genes, has two sets of chromosomes. Both strains had lutein synthesis metabolism pathway sharing identical synthetic genes ofcrtB,crtE,crtI,crtQ,crtL,crtR,atoB,dxs,dxr,ispD,ispE,ispDF,gcpE,ispG,ispH,ispA,ispBandispU.SphingopyxisUSTB-05 had hepatotoxins microcystins and nodularin metabolic pathways related to 16 genes (ald,ansA,gdhA,crnA,phy,ocd,hypdh,spuC,nspC,speE,murI,murD,murC,hmgL,bioAandglsA), while these genes were not found inSphingomonas morindaeNBD5. The unique protein sequences of strain NBD5 and strain USTB-05 were 155 and 199, respectively. The analysis of whole genome of the two Sphingomonadaceae strains provides insights into prokaryote evolution, the new pathway for lutein production and the new genes for environmental pollutant biodegradation.IMPORTANCEUnderstanding the functional genes related to the special functions of strains is essential for humans to utilize microbial resources. The ability ofSphingopyxisUSTB-05 to degrade hepatotoxins microcystins and nodularin has been studied in depth, however the complete metabolic process still needs further elucidation.Sphingomonas morindaeNBD5 can produce lutein, and it is necessary to determine whether there is a new pathway of lutein. In this study, the whole genome sequencing ofSphingopyxisUSTB-05 andSphingomonas morindaeNBD5 were performed for the first time. Lutein synthesis metabolic pathways and synthetic genes were discovered in Sphingomonadaceae. We predicted the existence of new lutein synthesis pathways and revealed most of the genes of the new synthesis pathways. A comparative analysis of the functional genes of the two strains revealed thatSphingopyxisUSTB-05 contains a large number of functional genes related to the biodegradation of hepatotoxins or hexachlorocyclohexane. Among them, the functional genes related to the biodegradation and metabolism of hexachlorocyclohexane had not been previously reported. These findings lay the foundation for the biosynthesis of lutein usingSphingomonas morindaeNBD5 orSphingopyxisUSTB-05 and the application ofSphingopyxisUSTB-05 for the biodegradation of hepatotoxins microcystins and nodularin or environmental pollutants.