bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional Incidence of Inflammatory Bowel Disease in a Czech Pediatric Population
Authors: Jabandziev Petr , Pinkasova Tereza , Kunovsky Lumir , Papez Jan , Jouza Martin , Karlinova Bara , Novackova Martina , Urik Milan , Aulicka Stefania , Slaby Ondrej , Bohosova Julia , Bajerova Katerina , Bajer Milan , Goel Ajay 
Published: February 2020

ABSTRACTObjectives:Inflammatory bowel disease (IBD) is today a global disease, the incidence of which is growing in the pediatric population. This prospective study aims to decipher IBD incidence and its trend in a pediatric population through 16 years in the South Moravian Region of the Czech Republic.Methods:We evaluated data concerning 358 pediatric patients with newly diagnosed IBD at University Hospital Brno, which is a gastroenterology center for the entire pediatric population (0–18 years) and cares for all pediatric IBD patients in the South Moravian Region (1,187,667 inhabitants).Results:The study encompassed 3,488,907 children during 16 years. We diagnosed 192 children (53.6%) with Crohn disease (CD), 123 (34.4%) with ulcerative colitis (UC), and 43 (12.0%) with IBD‐unclassified (IBD‐U). The incidence of IBD increased from 3.8 (CD 2.9, UC 0.9, and IBD‐U 0.0) per 100 000/year in 2002 to 14.7 (CD 9.8, UC 4.0, and IBD‐U 0.9) per 100,000/year in 2017 (P < 0.001). The overall IBD incidence per 100,000/year was 9.8 (95% confidence interval [CI]: 8.8‐‐10.9). Constituent incidences per 100,000/year were CD 5.2 (95% CI: 4.5‐‐6.0), UC 3.4 (95% CI: 2.8‐‐4.0), and IBD‐U 1.2 (95% CI: 0.9‐‐1.6). IBD incidence was projected to reach 18.9 per 100,000/year in 2022.Conclusions:The overall incidence of pediatric IBD in the Czech Republic is increasing, and especially that of CD, whereas trends in UC and IBD‐U appear to be constant. These data highlight the need to identify risk factors involved in the rising incidence of IBD.
Proton Pump Inhibitors, But Not H2-receptor Antagonists, Are Associated With Incident Fractures Among Kidney Transplant Recipients
Authors: Lyu Beini , Jorgenson Margaret R. , Hansen Karen E. , Djamali Arjang , Astor Brad C. 
Published: February 2020

Background.
Fractures are a common and burdensome problem among kidney transplant recipients (KTRs). Proton pump inhibitors (PPIs) are frequently used after kidney transplantation and have been associated with increased fracture risk in the general population. This study aimed to determine whether PPI use is associated with incidence of major fractures in KTRs.

Methods.
Using the Wisconsin Allograft Recipient Database, we identified 155 KTRs with a major fracture that occurred at least 12 months after transplantation. Controls were selected using incidence-density sampling. Use of PPIs and histamine 2-receptor antagonists (H2RA) during the year before the index date were identified.

Results.
A total of 155 cases were matched to 685 controls. Within 1 year before the index date, 68% of cases and 52% of controls used a PPI, and 16% of cases and 11% of controls used an H2RA. PPI use was associated with higher incidence of major fractures in unadjusted analysis (odds ratio [OR], 2.4; 95% CI, 1.6-3.5) and in adjusted analyses controlling for demographic and transplant-related covariates and use of corticosteroids, bisphosphonates, vitamin D and calcium supplements (OR, 1.9; 95% CI, 1.2-3.1). H2RA use was not associated with incidence of major fractures in adjusted analyses (OR, 1.0; 95% CI, 0.5-1.8). The associations between PPI use and fractures remained similar in analyses limited to spine and hip fractures.

Conclusions.
Use of PPIs, but not H2RAs, is associated with a higher risk of major fractures among KTRs. Clinicians should individualize PPI use in KTRs, evaluating the risks and benefits of prescribing and continuing PPIs in KTRs.
The Male Fertility Gene Atlas – A web tool for collecting and integrating data about epi-/genetic causes of male infertility
Authors: Krenz H. , Gromoll J. , Darde T. , Chalmel F. , Dugas M. , Tüttelmann F. 
Published: February 2020

AbstractInterconnecting results of previous OMICs studies is of major importance for identifying novel underlying causes of male infertility. To date, information can be accessed mainly through literature search engines and raw data repositories. However, both have limited capacity in identifying relevant publications based on aggregated research results e.g. genes mentioned in images and supplements. To address this gap, we present the Male Fertility Gene Atlas (MFGA), a web tool that enables standardised representation and search of aggregated result data of scientific publications. An advanced search function is provided for querying research results based on study conditions/phenotypes, meta information and genes returning the exact tables and figures from the publications fitting the search request as well as a list of most frequently investigated genes. As basic prerequisite, a flexible data model that can accommodate and structure a very broad range of meta information, data tables and images was designed and implemented for the system. The first version of the system is published at the URL https://mfga.uni-muenster.de and contains a set of 46 representative publications. Currently, study data for 28 different tissue types, 32 different cell types and 20 conditions is available. Also, ∼5,000 distinct genes have been found to be mentioned in at least ten of the publications. As a result, the MFGA is a valuable addition to available tools for research on the epi-/genetics of male infertility. The MFGA enables a more targeted search and interpretation of OMICs data on male infertility and germ cells in the context of relevant publications. Moreover, its capacity for aggregation allows for meta-analyses and data mining with the potential to reveal novel insights into male infertility based on available data.
Molecular dissection of neurodevelopmental disorder-causing mutations in CYFIP2
Authors: Schaks Matthias , Rottner Klemens 
Published: February 2020

AbstractActin remodelling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies described de novo mutations in the CYFIP2 subunit of WRC, which caused intellectual disability (ID) in humans. Although mutations had been proposed to effect WRC activation, no experimental evidence for this was provided. Here, we made use of CRISPR/Cas9-engineered B16-F1 cell lines that were reconstituted with ID-causing CYFIP variants in the context of compromised WRC activation with or without reduced Rac activities, which established that the majority of CYFIP2 mutations (5 out of 8) indeed cause constitutive WRC activation. Strikingly, activating mutations are positioned in a conserved WAVE- binding region mediating WRC transinhibition. As opposed to such gain-of-function mutations, a truncating mutant represented a loss-of-function variant, because it failed to interact with WRC components, and two mutants displayed no or at best a moderate increase of WRC activation. Collectively, our data show that CYFIP2 mutations frequently but not always coincide with WRC activation and suggest that normal brain development requires a delicate and precisely tuned balance of neuronal WRC activity.
A spatial model of CoVID-19 transmission in England and Wales: early spread and peak timing
Authors: Danon Leon , Brooks-Pollock Ellen , Bailey Mick , Keeling Matt 
Published: February 2020

AbstractBackgroundAn outbreak of a novel coronavirus, named CoVID-19, was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable cases of human-to-human transmission in England.MethodsWe adapted an existing national-scale metapopulation model to capture the spread of CoVID-19 in England and Wales. We used 2011 census data to capture population sizes and population movement, together with parameter estimates from the current outbreak in China.ResultsWe predict that a CoVID-19 outbreak will peak 126 to 147 days (∼4 months) after the start of person-to-person transmission in England and Wales in the absence of controls, assuming biological parameters remain unchanged. Therefore, if person-to-person transmission persists from February, we predict the epidemic peak would occur in June. The starting location has minimal impact on peak timing, and model stochasticity varies peak timing by 10 days. Incorporating realistic parameter uncertainty leads to estimates of peak time ranging from 78 days to 241 days after person-to-person transmission has been established. Seasonal changes in transmission rate substantially impact the timing and size of the epidemic peak, as well as the total attack rate.DiscussionWe provide initial estimates of the potential course of CoVID-19 in England and Wales in the absence of control measures. These results can be refined with improved estimates of epidemiological parameters, and permit investigation of control measures and cost effectiveness analyses. Seasonal changes in transmission rate could shift the timing of the peak into winter months, which will have important implications for health-care capacity planning.
Brain activation and connectivity in anorexia nervosa and body dysmorphic disorder when viewing bodies: relationships to clinical symptoms and perception of appearance
Authors: Moody Teena D , Morfini Francesca , Cheng Gigi , Sheen Courtney L , Kerr Wesley , Strober Michael , Feusner Jamie D 
Published: February 2020

AbstractAnorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared brain activation and connectivity in relevant networks when viewing images of others’ bodies and tested their relationships with clinical symptoms and subjective appearance evaluations. We acquired fMRI data from 64 unmedicated females (20 weight-restored AN, 23 BDD, 21 controls) during a matching task using photos of others’ bodies that were unaltered or spatial-frequency filtered. With general linear model and independent components analyses we compared brain activation and connectivity in visual, striatal, and parietal networks and performed univariate and partial least squares multivariate analyses to investigate relationships with clinical symptoms and appearance evaluations. BDD but not AN demonstrated hypoactivity in dorsal visual and parietal networks compared to controls. Yet, AN and BDD showed partially overlapping patterns of hyperconnectivity in the dorsal visual network and hypoconnectivity in parietal network compared with controls. Further, there were significant activity and connectivity differences between AN and BDD in both networks. In both groups, activity and/or connectivity were associated with symptom severity and appearance ratings of others’ bodies. AN and BDD demonstrate both distinct and partially overlapping aberrant neural phenotypes involved in body processing and visually encoding global features. Nevertheless, in each disorder, aberrant activity and connectivity show relationships to clinically relevant symptoms and subjective perception. Results have implications for understanding distinct and shared pathophysiology underlying perceptual distortions for appearance and may inform future novel treatment strategies.
Integrative kinomics reveals kinase-driven subtypes of gastric adenocarcinomas with sunitinib as a potential common inhibitor
Authors: Tapken Maria Johanna , Haag Georg Martin , Jäger Dirk , Fröhling Stefan , Mock Andreas 
Published: February 2020

AbstractMolecular subtyping of tumors promises a personalized stratification into different treatment regimens. In gastric adenocarcinoma, the four molecularly defined subtypeschromosomal instable (CIN), microsatellite unstable (MSI), genomically stable (GS)andEBV-positivesubtype have been proposed. Following an integrative kinomics approach this computational analysis aimed to predict the best kinase inhibitor for every molecular subtype of gastric adenocarcinomas using publicly available TCGA data (n=404). Intriguingly, using the regulatory network of gastric cancer to estimate protein activity, 43% of all samples could be identified to be kinase-driven. These samples were divided into three clusters with mutually exclusive kinase activities that were independent of the established molecular subtypes. Integrating the pattern of kinase overexpression with an unsupervised target landscape of 37 approved clinical kinase drugs revealed that sunitinib had the best target spectrum across the activated kinases in all three sample clusters. Future work is warranted to validate the kinase-driven subsets of gastric cancer and sunitinib as a potential common inhibitor.
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development
Authors: Parada Guillermo E. , Munita Roberto , Georgakopoulos-Soares Ilias , Fernandez Hugo , Metzakopian Emmanouil , Andres Maria Estela , Miska Eric A. , Hemberg Martin 
Published: February 2020

AbstractMicroexons, exons that are ≤30 nucleotides, were shown to play key roles in neuronal development, but are difficult to detect and quantify using standard RNA-Seq alignment tools. Here, we present MicroExonator, a novel pipeline for reproduciblede novodiscovery and quantification of microexons. We processed 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mouse. We detected 2,984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons alone segregates brain tissues by developmental time and further analysis suggest a key function for microexon inclusion in axon growth and synapse formation. Finally, we analysed single-cell RNA-seq data from the mouse visual cortex and we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell-type specific.
phyloregion: R package for biogeographic regionalization and spatial conservation
Authors: Daru Barnabas H. , Karunarathne Piyal , Schliep Klaus 
Published: February 2020

SummaryBiogeographical regionalization is the classification of regions in terms of their biotas and is key to understanding biodiversity patterns across the world. Previously, it was only possible to perform analysis of biogeographic regionalization on small datasets, often using tools that are difficult to replicate.Here, we presentphyloregion, a package for the analysis of biogeographic regionalization and spatial conservation in the R computing environment, tailored for mega phylogenies and macroecological datasets of ever-increasing size and complexity.Compared to available packages,phyloregionis three to four orders of magnitude faster and memory efficient for cluster analysis, determining optimal number of clusters, evolutionary distinctiveness of regions, as well as analysis of more standard conservation measures of phylogenetic diversity, phylogenetic endemism, and evolutionary distinctiveness and global endangerment.A case study of zoogeographic regionalization for 9574 species of squamate reptiles (amphisbaenians, lizards, and snakes) across the globe, reveals their evolutionary affinities, using visualization tools that allow rapid identification of patterns and underlying processes with user-friendly colours–for example– indicating the levels of differentiation of the taxa in different regions.Ultimately,phyloregionwould facilitate rapid biogeographic analyses that accommodates the ongoing mass-production of species occurrence records and phylogenetic datasets at any scale and for any taxonomic group into completely reproducible R workflows.
Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12
Authors: Chen Zhuoyao , Wasney Gregory A. , Picaud Sarah , Filippakopoulos Panagis , Vedadi Masoud , D’Angiolella Vincenzo , Bullock Alex N. 
Published: February 2020

ABSTRACTWnt signaling is critically dependent on dishevelled proteins (DVL1-3), which are required to assemble an intracellular Wnt signalosome at the plasma membrane. The levels of dishevelled proteins are strictly regulated by multiple E3 ubiquitin ligases that target DVL1-3 for ubiquitination and proteasomal degradation. The BTB-Kelch family protein KLHL12 is a substrate-specific adaptor for a Cullin-RING E3 ligase complex that contains Cullin3 and Rbx1. KLHL12 was the first E3 ligase to be identified for DVL1-3, but the molecular mechanisms determining its substrate interactions have remained unknown. Here, we mapped the interaction of DVL1-3 to a ‘PGXPP’ motif that is conserved in other known partners and substrates of KLHL12, including PLEXHA4, PEF1 and SEC31. A 20-mer peptide containing the DVL1 motif bound to the Kelch domain of KLHL12 with low micromolar affinity. In cells, the mutation or deletion of this motif caused a striking reduction in the binding, ubiquitination and stability of DVL1 confirming this sequence as a degron motif for KLHL12 recruitment. To determine the binding mechanism we solved a 2.4 Å crystal structure of the Kelch domain of KLHL12 in complex with a DVL1 peptide. The structure revealed that the DVL1 substrate adopted a U-shaped turn conformation that enabled hydrophobic interactions with all six blades of the Kelch domain β-propeller. Overall, these results define the molecular mechanisms determining DVL regulation by KLHL12 and establish the KLHL12 Kelch domain as a new protein interaction module for a novel proline-rich motif.
Dynamic Vision Training Transfers Positively to Batting Performance Among Collegiate Baseball Batters
Authors: Liu Sicong , Ferris Lyndsey M. , Hilbig Susan , Asamoa Edem , LaRue John L. , Lyon Don , Connolly Katie , Port Nicholas , Appelbaum L. Gregory 
Published: February 2020

AbstractA growing body of evidence demonstrates visual, perceptual, and oculomotor abilities contribute to batting performance in baseball and there is interest in whether training such abilities can transfer positively to batting performance. The current study tested this question through a pre-registered randomized, and placebo-controlled intervention, conducted with 24 collegiate baseball players at two Division 1 universities. Athletes were randomized to receive either dynamic vision training consisting of stroboscopic, anticipatory timing, and eye quickness drills, or placebo drills stylized after control procedures in previous vision therapy studies. Generalized near-transfer was tested via a digital visual-motor task battery (n= 20), while sports-specific intermediate and far transfer of training were evaluated through instrumented batting practice metrics (n= 14) and box score performance in NCAA-sanctioned games (n= 12). The effects of training group were tested on these outcome measures while controlling for covariates such as pre-training expectations and site. Participants averaged 8.50 hours of training with no significant training group differences in adherence, expectations, or baseline assessments. ANCOVA revealed no group differences in measures of visual-motor skills or NCAA game statistics. However, batting practice demonstrated significant improvements in launch angle (p= 0.002, Cohen’sd= 0.74) and hit distance (p< 0.001, Cohen’sd= 0.70) for the active cohort relative to the placebo control. This controlled and pre-registered pilot study therefore provides preliminary evidence that vision training may improve batting practice performance, creating new opportunities for the transfer of skill training and warranting further study.Pre-RegistrationAt Open Science Framework on August 9, 2018. DOI 10.17605/OSF.IO/496RX. Accessible athttps://osf.io/jxh8u
Long-term repeatability in social behaviours suggests stable social phenotypes in wild chimpanzees
Authors: Tkaczynski Patrick J. , Mielke Alexander , Samuni Liran , Preis Anna , Wittig Roman , Crockford Catherine 
Published: February 2020

AbstractAnimals living in social groups navigate challenges when competing and cooperating with other group members. Changes in demographics, dominance hierarchies or ecological factors, such as food availability or disease prevalence, are expected to influence decision-making processes regarding social interactions. Therefore, it could be expected individuals show flexibility in social behaviour over time to maximise the fitness benefits of social living. To date, research across species has shown that stable inter-individual differences in social behaviour exist, but mostly over relatively short data collection time periods. Using data spanning over 20 years, we demonstrate that multiple social behaviours are repeatable over the long-term in wild chimpanzees, a long-lived species occupying a complex fission-fusion society. We controlled for temporal, ecological and demographic changes, limiting pseudo-repeatability. We conclude that chimpanzees living in natural ecological settings have relatively stable long-term social phenotypes over years that may be independent of life history stage or strategies. Our results add to the growing body of literature suggesting consistent individual differences in social tendencies are more likely the rule rather than the exception in group-living animals.
Enhancing CRISPR deletion via pharmacological delay of DNA-PK
Authors: Bosch Núria , Medová Michaela , Esposito Roberta , Pulido-Quetglas Carlos , Zimmer Yitzhak , Johnson Rory 
Published: February 2020

AbstractCRISPR-Cas9 deletion (CRISPR-del) is the leading approach for eliminating DNA from mammalian cells and underpins a variety of genome-editing applications. Target DNA, defined by a pair of double strand breaks (DSBs), is removed during non-homologous end-joining (NHEJ). However, the low efficiency of CRISPR-del results in laborious experiments and false negative results. Using an endogenous reporter system, we demonstrate that temporary inhibition of DNA-dependent protein kinase (DNA-PK) – an early step in NHEJ - yields up to 17-fold increase in DNA deletion. This is observed across diverse cell lines, gene delivery methods, commercial inhibitors and guide RNAs, including those that otherwise display negligible activity. Importantly, the method is compatible with pooled functional screens employing lentivirally-delivered guide RNAs. Thus, delaying the kinetics of NHEJ relative to DSB formation is a simple and effective means of enhancing CRISPR-deletion.